Skin and Soft Tissue Flashcards

Question

Regarding metastatic melanoma, which of the following is FALSE? A. Surgery or patients with Stage IV melanoma confers a survival advantage over systemic medical therapy alone. B. The primary objective of metastatectomy or Stage IV melanoma is resection of all known disease. C. Recurrent Stage IV disease is not a contraindication to surgery or metastatic melanoma. D. In-transit metastases occur less than 2 cm from the primary melanoma and are located between the primary melanoma and the regional lymph node basin. E. More than 50% of patients with Stage IV melanoma will develop brain metastases.

Answer 1

D. In-transit metastases occur less than 2 cm from the primary melanoma and are located between the primary melanoma and the regional lymph node basin. In appropriately selected patients with Stage IV melanoma, surgery should be considered as initial therapy. Analysis of MSL -1 data demonstrated improved survival in patients with Stage IV melanoma who underwent surgery with or without systemic medical therapy compared with systemic medical therapy alone. Multiple sites of disease and even recurrent Stage IV disease are not contraindications to resection. The most important preoperative considerations include resectability of all known disease, tumor biology such as tumor volume doubling time, and patient comorbidities. The most common metastatic sites for melanoma are skin, lung, lymph nodes, brain, liver, and gastrointestinal tract. In-transit metastasis is defined as intra-lymphatic tumor in skin or subcutaneous tissue more than 2 cm from the primary tumor but not beyond the nearest regional lymph node basin. The lung is a typical site of metastasis and good evidence or pulmonary metastatectomy exists. Melanoma is the most common metastatic tumor in the small bowel and may present as pain, obstruction, bleeding, palpable mass or weight loss. More than 50% of patients with Stage IV melanoma will develop brain metastasis. Because of this, NCCN Version 4 (2014) Melanoma recommends consideration of annual brain MRI in addition to more frequent whole body PET/CT as a part of routine surveillance in patients with Stage IV disease.

Answer 2

C. The most common histologic subtypes or extremity sarcomas include liposarcoma and malignant fibrous histiocytoma. Regarding pre-operative imaging of the tumor, MRI is generally preferred for extremity sarcomas, while C tends to be preferable for abdominal and retroperitoneal sarcomas. However, there has not been demonstrated a statistically significant difference between the two modalities. High-quality cross sectional imaging is nevertheless critical for preoperative evaluation and planning. PE can give information regarding the grade, prognostication, and response to chemotherapy in select high grade, large, deep sarcomas, and can be considered for use, but does not have a role in routine evaluation of all sarcomas. Incisional biopsy may be required, but generally speaking, or both extremity and retroperitoneal sarcomas, needle core biopsy (with or without image guidance) provides adequate tissue sampling with good diagnostic correlation to final pathology. However, when unavailable or inadequate, incisional biopsy or extremity sarcomas remains a reasonable diagnostic option. Care should be taken if an incisional biopsy is necessary. Incisions should be oriented longitudinally and thoughtully, as re-excision of biopsy site will be necessary with definitive operation. In some selected institutions with clinical and pathologic expertise, FNA may be adequate, but should probably not be considered adequate at low-volume centers. There are over 50 histologic subtypes of soft tissue sarcoma recognized. Overall, the most common subtypes are liposarcoma, malignant fibrous histiocytoma (MFH), and leiomyosarcoma, however the prevalence is site specific. The most common types or extremity sarcomas are liposarcoma and MFH, while retroperitoneal sarcomas are more commonly liposarcoma and leiomyosarcoma. GIST and leiomyosarcoma are the histological types found in visceral tumors. Overall, lung is the most common site of metastasis or extremity sarcomas. For visceral tumors, liver is more common. Chest CT is generally advocated for extremity sarcomas to rule out metastatic disease. Due to the complexity, rarity, and histology- based therapy for soft tissue sarcomas, prior to initiating therapy, all patients should be evaluated by a multidisciplinary team with expertise in sarcoma therapy.

Answer 3

B. Surgical margin of 1 to 2 cm should be sought whenever possible. Until the early 1980s, amputation remained a primary therapy or most extremity sarcomas. In 1982, Rosenberg and colleagues at the National Cancer Institute published a randomized trial of amputation vs. limb-sparing surgery plus radiation and demonstrated equivalent overall survival and acceptable local recurrence rate of 15% with limb-salvage versus 0% with amputation. Currently, limb salvage surgery can be safely performed in over 90% of patients with extremity sarcoma with excellent local recurrence rates. Proximity of critical structures (bone, nerves, blood vessels, etc.) should be considered carefully during pre-operative planning and the expected functional outcome assessed to assist in making the decision for limb salvage versus amputation. Careful pre-operative planning is imperative or successful resection of these tumors. Failure to obtain a negative surgical margin is the most important risk factor for local recurrence. Careful scrutiny of pre-operative imaging can result in improved outcomes by allowing the surgeon to have a thorough understanding of the extent of the tumor and relationship to local structures. Functional outcomes are also improved by careful consideration of the extent of resection required. Similarly, this allows for appro- priate consultation with subspecialists including plastic or vascular surgeons pre-operatively when anticipated being necessary. Wide margins should be the goal of therapy. A margin of 1 to 2 cm of normal tissue can help to minimize the risk of local recurrence. However, strong tissues such as fascia can severely limit the spread of most types of sarcoma into adjacent structures. Therefore, a narrow fascial margin may be acceptable where such a narrow margin of muscle or fat would likely result in an increased risk of recurrent disease. In some cases, such as retroperitoneal sarcomas, wide margins may not be feasible. Resection of nerves and blood vessels is occasionally unavoidable, but can often be avoided by careful skeletonization of blood vessels and resection of the perineurium along with the tumor. The concept of “planned positive margin” is feasible in many cases with the use of adjuvant radiation therapy. As long as the structure of concern is not fixed to the tumor, this carefully planned positive margin provides similar outcomes to controls with negative margins. Neo- adjuvant radiation has been advocated in this setting or “marginally resectable” tumors in order to allow a negative margin functional resection. Histologic subtype does play an important actor in planning surgical intervention. Well-differentiated liposarcoma (formerly called atypical lipomas) have similar recurrence rate to other types of sarcoma, but metastatic disease is rare, so surgical resection can be less aggressive when necessary. Dermatofibrosarcoma protuberans (DFSP) and myxo brosarcoma are particularly difficult due to the common finding of microscopic tentacles that extend laterally rom these lesions. DFSP has a tendency to respect fascial borders, whereas myxofibrosarcoma o en penetrates fascia and can have multifocal skip lesions, so these factors must be considered. Lymph node metastasis is rare in STS in general, but can be seen more commonly with epithelioid or clear cell variants. For this reason, sentinel lymph node biopsy can give prognostic information, so though no clear therapeutic benefit has been shown, it may be considered in this setting.

Answer 4

C. Radiation therapy has been shown to be of benefit in the treatment of sarcomas. Radiation therapy has been repeatedly demonstrated to be of benefit in disease free survival, though not significantly different overall survival. There remains some controversy regarding the optimal timing of the radiation therapy. When comparing neoadjuvant versus adjuvant therapy, local control rate is similar. However, preoperative radiation has been found to double wound complications in the months following surgery compared to increased rates of long term complications such as fibrosis, edema, and joint stiffness with postoperative radiation. External beam, brachytherapy, and intraoperative radiotherapy have all been used with some success. Patients at low risk for recurrence (i.e.,small(<5cm) superficial tumors, low grade tumors, wide surgical margins) may not derive a significant benefit from radiation and may be treated with surgery alone. Surgery is the dominant therapeutic modality for extremity, retroperitoneal, and visceral sarcomas. Complete surgical resection is the primary actor in outcomes. Only a few clinical trials have demonstrated a statistically significant improvement in outcomes with adjuvant chemotherapy. Specific histology-directed regimens have shown the most promise and have achieved excellent and sustained results in specific subtypes to include gastrointestinal stromal tumors (GIST), rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma. Patients with an isolated metastasis can be considered or metastatectomy if resection with or without chemotherapy for radiation may result in a cure. This may include removal of limited disease in a single organ or regional node dissection if nodal metastasis is isolated. Specifically in the setting of isolated lung metastasis, median survival is lengthened from 11 to 33 months compared to observation. Patients with widely metastatic disease may be considered for palliation using a variety of modalities including surgery, chemotherapy, radiation, embolization, and ablation procedures. Local recurrence rate varies with the site of the initial tumor and the adequacy of surgical resection, but is significant. Local recurrence after treatment for extremity soft tissue sarcoma approaches one out of three patients. The median disease- free interval is 18 months, but can be quite remote. Considerations for treatment of recurrent disease are similar to primary disease and can include reexcision, chemo- therapy, and radiation, often with similar success to the primary tumors or extremity sarcomas. Recurrence of visceral and retroperitoneal sarcomas often is unable to be completely re-excised. GIST is the most common mesenchymal tumor of the GI tract, and has gained significant interest in recent years. The discovery of the KI proto-oncogene mutation present in the majority of GIS tumors led to the ability to specifically target GIS tumors at a molecular level with the tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis Pharmaceutical, Basel, Switzerland). This advancement marks a new era in treating solid tumors with specific molecular targeting. Surgery remains of vital importance, but several studies have demonstrated improved disease-free and overall survival for patients at significant risk for recurrence who are treated adjuvantly with tyrosine kinase inhibitors, so this has become an important, disease-specific therapy or these rare tumors.

Answer 5

C. Physical examination should include thorough exam of all accessible lymph node basins as well as potential sites of a primary malignancy. In patients without a tissue diagnosis of malignancy, but concern for lymphoma, FNA is generally not considered to be adequate or diagnosis. FNA may be able to identify some cases of metastatic carcinoma (i.e., breast, lung, etc.) but is limited in hematologic malignancies (especially lymphoma) as lymph node architecture is a critical pathologic component to making these diagnoses. FNA may be useful in searching or recurrent disease. As knowledge and use of molecular markers is expanded in the future, FNA may become a viable alternative to open biopsy of suspicious nodes. When lymphadenopathy is generalized the largest, most suspicious, and accessible note is selected for biopsy. The diagnostic yield does vary by site with inguinal nodes having the lowest yield and supraclavicular nodes the highest. Careful and appropriate handling of tissue specimens is critical to allow pathologic diagnosis. Adequate tissue sampling is critical to allow assessment of nodal architecture. Specimens should be submitted to pathology dry or in saline, not formalin or other preservative, in order to allow flow cytometric and immunohistochemical studies to supplement traditional pathology. The differential diagnosis or lymphadenopathy is extremely broad and includes malignancy (lymphoma, metastatic disease), infections (cat-scratch disease, HIV, mononucleosis, tuberculosis, etc.), autoimmune disorders, iatrogenic causes such as medications and unusual causes including sarcoidosis and Kawasaki’s disease. A thorough history and physical can be used to help narrow this broad differential. In patients without concerning signs or symptoms suggestive o malignancy or other severe disease (e.g., B symptoms, etc.) a period of observation of four to six weeks is appropriate. If the lymphadenopathy persists beyond this period of observation, further evaluation to include CBC and chest X-ray should be pursued. Other testing to include serology or CMV, heterophile testing (monospot), PPD, HIV testing, RPR, and so on may be utilized based upon the history and physical and specific concerns. Several non-specific laboratory tests reflecting inflammation to include ESR, CRP, and fibrinogen may be used, but do not typically help narrow the differential diagnosis. Lactate dehydrogenase (LDH) is often similarly non-specific though very high levels may suggest a lymphoid neoplasm. Ultimately, persistent lymphadenopathy without an obvious etiology warrants lymph node biopsy as discussed above. Fever, chills, night sweats, and weight loss > 10% over 6 months are the classically described “B” symptoms associated with lymphoma and the presence of these findings should increase the suspicion of this diagnosis and prompt a more aggressive approach to diagnosis. Careful physical exam should be an important part of the evaluation of every patient with lymphadenopathy. The differential diagnosis is highly dependent upon the presence of generalized versus isolated lymphadenopathy and the lymph node basin involved when localized. Examining sites of possible metastatic spread, or example breast, skin, oropharynx, and soon is important in narrowing the differential.

Answer 6

E. Mucosa-associated lymphoid tissue (MALT) lymphoma may be definitively treated with H. pylori eradication in its early stages. Lymphoma refers to a spectrum of diseases including Hodgkin’s and Non-Hodgkin’s (NHL) lymphomas with multiple subtypes within each group. The role of the surgeon in patients with lymphoma is limited. By far, the most important role of the surgeon is in assisting with the diagnosis by means of lymph node biopsy. Once the diagnosis has been made, the treatment of lymphoma is overwhelmingly the role of chemotherapy and radiation. Historically, surgery was more involved through the use of staging laparotomy, but this is now rarely indicated with the availability and use of PET/CT for staging purposes. Surgical intervention to include splenectomy is limited to significantly symptomatic situations such as anemia, thrombocytopenia, neutropenia and massive splenomegaly, and should be done only in close consultation with oncology. Staging for lymphoma is based upon modifications of the original Ann Arbor classification, initially described for Hodgkin’s lymphoma, but now also used or NHL. Staging is based upon number and location of lymph node groups, extranodal involvement, and has modifiers to signify presence or absence of B symptoms. Several risk factors for lymphoma have been identified. There has been a significant increase in incidence since the 1970s, which has been partially explained by the HIV epidemic. Other contributors to the increase include other infections (i.e. Helicobacter pylori-induced mucosal associated lymphoid tissue (MALT) lymphoma), autoimmune diseases, immunosuppression (as with organ transplant), environmental actors including pesticides, and aging of the population (NHL increases in incidence with age and peaks during the fifth through seventh decades). Hodgkin’s lymphoma is more common in higher socioeconomic groups and less common in Asian populations. MALT lymphoma has been shown to be dependent on Helicobacter pylori infection. Gastric inflammatory response to this infection stimulates the acquisition of genetic abnormalities and malignant transformation of B cells. In the early stages of this disease, H. pylori eradication can reverse the disease process in as many of 77% of patients. However, in later stages of the disease, further genetic injury to these malignant cells make the tumor resistant to bacterial eradication, so more aggressive therapy including chemotherapy and radiation is indicated. Like other forms of lymphoma, surgery is generally reserved or rare situations with complication such as life-threatening hemorrhage.

Answer 7

B. Treated with running water or saline for 2 hours The treatment for both types of injuries is based on neutralization of the inciting solution and starts with running distilled water or saline over the affected skin for at least 30 minutes for acidic solutions and 2 hours for alkaline injuries. It should be noted that neutralizing agents do not offer a significant advantage over dilution with water, may delay treatment, and may worsen the injury due to the exothermic reaction that may occur. The clinician observes and treats based on the degree of presentation. Many cases are successfully managed conservatively with topical emollients and oral analgesics, and most cases result in edema, erythema, and induration. If signs of deep second-degree burns develop, local wound care may include debridement, Silvadene, and protective petroleum gauze. In severe cases, injury to the underlying vessels, bones, muscle, and tendon may occur, and these cases may be managed within 24 hours by liposuction through a small catheter and then saline injection. Surgery is indicated for tissue necrosis, uncontrolled pain, or deep-tissue damage. Antibiotics should not be administered unless signs of infection are present. (See Schwartz 10th ed., p. 479.)

Answer 8

A. Application of calcium carbonate gel Injuries that have specific additional treatments include hydrofluoride burns. Hydrofluoride is found in air conditioning cleaners and petroleum refineries. Treatment of hydrofluoride burns should include topical or locally injected calcium gluconate to bind fluorine ions. Intra-arterial calcium gluconate can provide pain relief and preserves arteries from necrosis, whereas intravenous (IV) calcium repletes resorbed calcium stores. Topical calcium carbonate gel and quaternary ammonium compounds detoxify fluoride ions. This mitigates the leaching of calcium and magnesium ions by the hydrofluoric acid from the affected tissues and prevents potentially severe hypocalcemia and hypomagnesemia that predispose to cardiac arrhythmias. (See Schwartz 10th ed., pp. 479—480.)

Answer 9

C. Zone of stasis Exposure of the skin to thermal extremes disrupts its primary function as a barrier to heat loss, evaporation, and microbial invasion. The depth and extent of injury are dependent on the duration and temperature of the exposure. The pathophysiology and management are discussed elsewhere in this book. Briefly, the epicenter of the injury undergoes a varying extent of necrosis (depending on the exposure), otherwise referred to as the zone of coagulation, which is surrounded by the zone of stasis, which has marginal perfusion and questionable viability. This is the area of tissue that is most amenable to salvage by appropriate resuscitative and wound management techniques, which would theoretically limit the extent of injury. The outermost area of skin shows characteristics similar to other inflamed tissues and has been designated the zone of hyperemia. The degree of burn corresponds to histologic layers of the affected dermis and correlates with management and prognosis pertaining to timeline of healing and magnitude of scarring. (See Schwartz 10th ed., p. 480.)

Answer 10

B. Stage 2 Tissue pressures that exceed the pressure of the microcirculation (30 mm Hg) result in tissue ischemia. Frequent or prolonged ischemic insults will ultimately result in tissue damage. Areas of bony prominence are particularly prone to ischemia, the most common areas being ischial tuberosity (28%), trochanter (19%), sacrum (17%), and heel (9%). Tissue pressures can measure up to 300 mm Hg in the ischial region during sitting and 150 mm Hg over the sacrum while lying supine. Muscle is more susceptible than skin to ischemic insult due to its relatively high metabolic demand. Wounds are staged as follows: stage 1, nonblanching erythema over intact skin; stage 2, partial-thickness injury (epidermis or dermis)— blister or crater; stage 3, full-thickness injury extending down to, but not including, fascia and without undermining of adjacent tissue; and stage 4, full-thickness skin injury with destruction or necrosis of muscle, bone, tendon, or joint capsule. (See Schwartz 10th ed., p. 482.)

Answer 11

C. Penicillin Actinomycosis should be considered in the differential diagnosis of any acute, subacute, or chronic cutaneous swelling of the head and neck. The cervicofacial form of Actinomycètes infection is the most common presentation, typically as an acute pyogenic infection in the submandibular or paramandibular area, but infection could be elsewhere in the mandibular and maxillary regions. The primary skin infection may spread to adjacent structures such as the scalp, orbit, ears, and other areas. Oral infection may spread to the hypopharynx, larynx, trachea, salivary glands, and sinuses. Actinomycosis can spread beyond boundaries of tissue planes and may also mimic chronic osteomyelitis. Treatment consists of a combination of penicillin therapy and surgical debridement. Debulking and debriding infected tissue arising from sinus tracts and abscess cavities inhibit actinomycosis growth in most cases. (See Schwartz 10th ed., p. 484.)

Answer 12

B. ß-lactam Treatment of nonpurulent, complicated cellulitis can begin with a ß-lactam, with methicillin-resistant Staphylococcus aureus (MRSA) coverage added if no response is observed. Empiric MRSA coverage is warranted in all other complicated skin and subcutaneous infections. Vancomycin is the mainstay of therapy, although it is inferior to ß-lactams for methicillin-sensitive S. aureus (MSSA) and has a relatively slow onset of efficacy in vitro. Linezolid, daptomycin, tigecycline, and telavancin are other FDA-approved alternatives for MRSA treatment. Clindamycin is also approved for S. aureus; however, resistance may develop, and diarrhea can occur in up to 20% (Clostridium difficile related). (See Schwartz 10th ed.,p.483.)

Answer 13

C. Excision with 2- to 4-mm normal margin Basal cell carcinoma (BCC) arises from the basal layer of nonkeratinocytes and represents the most common tumor diagnosed in the United States. Annually it accounts for 25% of all diagnosed cancers and 75% of skin cancers. The primary risk factor for disease development is sun exposure (ultraviolet [UV] B rays more than UVA rays) particularly during adolescence; however, other factors include immune suppression (ie, organ transplant recipients, human immunodeficiency virus [HIV]), chemical exposure, and ionizing radiation exposure. BCC can also be a feature of inherited conditions such as xeroderma pigmentosa, unilateral basal cell nevus syndrome, and nevoid BCC syndrome. The natural behavior of BCC is one of local invasion rather than distant metastasis. Untreated BCC can result in significant morbidity. Thirty percent of cases are found on the nose, and bleeding, ulceration, and itching are often part of the clinical presentation. (See Schwartz 10th ed., p.486.)

Answer 14

C. Are typically found on the scalp of females There are three types of cutaneous cysts: epidermal, dermoid, and trichilemmal. All of these benign entities comprise epidermis that grows toward the center of the cyst, resulting in central accumulation of keratin to form a cyst. All clinically appear as a white, creamy substance-containing subcutaneous, thin-walled nodule. Epidermal cysts are the most common cutaneous cyst and histologically characterized by mature epidermis complete with granular layer. Trichilemmal cysts are the second most common lesion; they tend to form on the scalp of females, have a distinct odor after rupture, histologically lack a granular layer, and have an outer layer resembling the root sheath of a hair follicle. Dermoid cysts are congenital, found between the forehead to nose tip, and contain squamous epithelium, eccrine glands, and pilosebaceous units, occasionally developing bone, tooth, or nerve tissue. The eyebrow is the most frequent site of presentation. These cysts are commonly asymptomatic but can become inflamed and infected, thus necessitating incision and drainage. After the acute phase subsides, the entire cyst should be removed to prevent recurrence. (See Schwartz 10th ed., p. 486.)

Answer 15

D. 3 years It is critical for each patient to have routine annual follow-up that includes full-body skin examinations. Sixty-six percent of recurrences develop within 3 years, and with a few exceptions occurring decades after initial treatment, the remaining recur within 5 years of initial treatment. A second primary BCC may develop after treatment and, in 40% of cases, presents within the first 3 years after treatment. (See Schwartz 10th ed.,p. 487.)

Answer 16

A. UV exposure Squamous cell carcinoma (SCC) is the second most common skin cancer, accounting for approximately 100,000 cases each year and generally afflicting individuals of lighter skin color. The primary risk factor and driving force for the development of this common cancer is UV exposure; however, other risks include environmental factors such as chemical agents, physical agents (ionizing radiation), psoralen and UVA (PUVA), HPV-16 and -18 infections (immunosuppression), and smoking. Chronic nonhealing wounds, burn scars, and chronic dermatosis are other risk factors, and many darker skin individuals who develop SCC often have a history of one of these risk factors. Heritable conditions such as xeroderma pigmentosum, epidermolysis bullosa, and oculocutaneous albinism are predisposing risk factors. (See Schwartz 10th ed., p. 487.)

Answer 17

C. 6 mm Melanoma most commonly manifests as cutaneous disease, and clinical characteristics include an Asymmetric outline, changing irregular Borders, Color variations, Diameter greater than 6 mm, and Elevation (ABCDE). Other key clinical characteristics include a pigmented lesion that has enlarged, ulcerated, or bled. Amelanotic lesions appear as raised pink, purple, or normal-colored skin papules and are often diagnosed late. (See Schwartz 10th ed., p. 488.)

Answer 18

B. Lung The most common sites of distant metastasis are the lungs and liver followed by the brain, gastrointestinal tract, distant skin, and subcutaneous tissue. A limited subset of patients with small-volume, limited distant metastases to the brain, gastrointestinal tract, or distant skin will be cured with resection or gamma knife radiation. Liver metastases are better dealt without surgical resection unless they arise from an ocular primary. (See Schwartz 10th ed.,p. 491.)

Answer 19

C. Superficial spreading Melanoma growth most commonly starts as a localized, radial growth phase followed by a vertical growth phase that determines metastatic risk. The subtypes of melanoma include lentigo maligna, superficial spreading, acral lentiginous, mucosal, nodular, polypoid, desmoplastic, amelanotic, and soft tissue. The most common subtype is superficial spreading, accounting for 70% of cases. (See Schwartz 10th ed., p.488.)

Answer 20

D. Exclusively metastasizes to the liver Ocular melanoma is the most common noncutaneous disease site, and treatment includes photocoagulation, partial resection, radiation, or enucleation. Ocular melanomas exclusively metastasize to the liver and not regional lymph nodes, and some patients benefit from liver resection. (See Schwartz 10th ed.,p. 491.)

Answer 21

D. Recurrence is uncommon. This is a rare and aggressive neuroendocrine tumor of the skin most commonly found in white men and diagnosed at a mean age of 70 years. Risk factors include UV radiation, PUVA, and immunosuppression. Approximately one in three cases present on the face, with the remainder occurring on sun-exposed skin. A rapidly growing, flesh-colored papule or plaque characterizes the disease. Regional lymph nodes are involved in 30% of patients, and 50% will develop systemic disease (skin, lymph nodes, Ever, lung, bone, brain). There are no standardized diagnostic imaging studies for staging, but computed tomography (CT) of the chest, abdomen, and pelvis and octreotide scans may provide useful information when clinically indicated. After examining the entire skin for other lesions, treatment should begin by evaluating the nodal basins.

Answer 22

C. Acral lentiginous Nodular melanoma accounts for 15 to 30% of melanomas, and this variant is unique because it begins with a vertical growth phase that partly accounts for its worse prognosis. Lentigo maligna is typically found in older individuals and primarily located in the head and neck region. The acral lentiginous variant accounts for 29 to 72% of melanomas in dark-skinned individuals, is occasionally seen in Caucasians, and is found on palmar, plantar, and subungual surfaces. (See Schwartz 10th ed.,p. 488.)

Answer 23

A. Excision is the treatment of choice Kaposi sarcoma is diagnosed after the fifth decade of life and predominantly found on the skin but can occur anywhere in the body. In North America, the Kaposi sarcoma herpes virus is transmitted via sexual and nonsexual routes and predominantly affects individuals with compromised immune systems such as those with HIV and transplant recipients on immune-suppressing medications. Clinically, Kaposi sarcoma appears as multifocal, rubbery blue nodules. Treatment of acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma is with antiviral therapy, and many patients experience a dramatic treatment response. Those individuals who do not respond and have limited mucocutaneous disease may benefit from cryotherapy, photodynamic therapy, radiation therapy, intralesional injections, and topical therapy. Surgical biopsy is important for disease diagnosis, but given the high local recurrence and the fact that Kaposi sarcoma represents more of a systemic rather than local disease, the benefit of surgery is limited and generally should not be pursued except for palliation. (See Schwartz 10th ed., p. 492.)

Answer 24

B. Site of metastasis Melanoma is characterized according to the American Joint Committee on Cancer (AJCC) as localized disease (stage I and II), regional disease (stage III), or distant metastatic disease (stage IV). Overall tumor thickness, ulceration, and mitotic rate are the most important prognostic indicators of survival. If a sentinel node contains metastatic melanoma, the number of positive nodes; thickness, mitotic rate, and ulceration of the primary tumor; and patient age determine prognosis. With clinically positive nodes, the number of positive nodes, primary tumor ulceration, and patient age determine prognosis. The site of metastasis is strongly associated with prognosis for stage IV disease, and elevated lactate dehydrogenase (LDH) is associated with a worse prognosis. (See Schwartz 10th ed., p. 488.)

Answer 25

A. Resection of the primary only Nonmetastatic in-transit disease should undergo excision to clear margins when feasible. However, disease not amenable to complete excision derives benefit from isolated limb perfusion (ILP) and isolated limb infusion (ILI) (Fig. 16-1). These two modalities are used to treat regional disease, and their purpose is to administer high doses of chemotherapy, commonly melphalan, to an affected limb while avoiding systemic drug toxicity. ILI was shown to provide a 31% response rate in one study, while hyperthermic ILP provided a 63% complete response rate in an independent study. (See Schwartz 10th ed., Figure 16-15, p. 491.)

Answer 26

B. BCC The most common form of BCC (60%) is the nodular variant, characterized by raised, pearly pink papules and occasionally a depressed tumor center with raised borders giving the classic “rodent ulcer” appearance. This variant tends to develop in sun-exposed areas of individuals older than 60 years. Superficial BCC accounts for 15% of BCC, is diagnosed at a mean age of 57 years, and typically appears on the trunk as a pink or erythematous plaque with a thin pearly border. The infiltrative form appears on the head and neck in the late 60s with similar clinical appearance to the nodular variant. An important variant to keep in mind is the pigmented variant of nodular BCC because this may be difficult to differentiate from nodular melanoma. Other important subtypes include the morpheaform variant, accounting for 3% of cases and characterized by indistinct borders with a yellow hue, and fibroepithelioma of Pinkus. Histologic subtypes of BCC include nodular and micronodular (50%), superficial (15%), and infiltrative. (See Schwartz 10th ed., p. 486.)

Answer 27

C. Hidradenitis suppurativa Hidradenitis suppurativa is a chronic inflammatory disease presenting as painful subcutaneous nodules. Patients experience appreciable physical, psychological, and economical hardship and decreased quality of life when compared with patients who suffer from other chronic dermatologic disease such as psoriasis and alopecia. It is characterized by multiple abscesses, inter-networking sinus tracts, foul-smelling exudate from draining sinuses, inflammation in the dermis, both atrophic and hypertrophic scars, ulceration, and infection, which may extend deep into the fascia. The diagnosis is made clinically without the need for imaging or laboratory tests. (See Schwartz 10th ed.,p. 467.)

Answer 28

D. Corticosteroid use is a primary part of therapy. These inflammatory diseases represent a spectrum of an autoimmune reaction to stimuli such as drugs that result in structural defects in the epidermal-dermal junction. The cutaneous manifestations of toxic epidermal necrolysis syndrome (TENS) follow a prodromal period reminiscent of an upper respiratory tract infection. A symmetrical macular eruption follows starting from the face and trunk and spreading to the extremities. Typically, a Nikolsky sign develops in which lateral pressure causes the epidermis to detach from the basal layer. The macular eruption evolves into blisters, causing an extensive superficial partial-thickness skin injury with exposed dermis. (See Schwartz 10th ed., p. 477.)

Answer 29

B. Extramammary Paget disease This rare adenocarcinoma of apocrine glands arises in perianal and axillary regions and in genitalia of men and women. Clinical presentation is that of erythematous or nonpigmented plaques with an eczema-like appearance that often persist after failed treatment from other therapies. An important characteristic and one that the surgeon must be acutely aware of is the high incidence of concomitant other malignancies with this cutaneous disease. Forty percent of cases are associated with primary gastrointestinal and genitourinary malignancies, and a diligent search should be made after a diagnosis of extramammary Paget disease is made. Treatment is surgical resection with negative microscopic margins, and adjuvant radiation may provide additional locorégional control. (See Schwartz 10th ed., p. 493.)

Answer 30

1) Localized RADIAL growth phase | 2) VERTICAL growth phase (determines metastatic risk)

Answer 31

Suspicious lesion: Do a BIOPSY. Small lesions (up to 1.5cm) - Excisional biopsy - 1 to 3mm margins - Deep margin up to subcutaneous fat - Orient biopsy with definitive wide excision in mind (parallel to LN) Larger lesions - Incision biopsy of the most raised/pigmented area - Positive (incomplete) margins, but deep margin up to subcutaneous fat Borderline lesions - Shave biopsy - Decreased index of suspicion for melanoma ``` Aesthetic areas (ie, face) - Punch biopsy ```

Answer 32

PRIMARY TUMOR (No evidence of regional disease— Stage I & II) 1. PE 2. CXR 3. LDH 4. Sentinel Lymphadenectomy LOCOREGIONAL DISEASE (Stage III) 1. PE 2. CXR 3. LDH 4. Sentinel lymphadenectomy 5. WAB CT 6. Chest CT 7. Pelvic CT (if disease below waist) 8. Neck CT (if head and neck area) 9. Cranial MRI DISTANT METS (Stage IV) 1. PE 2. CXR 3. LDH 4. WAB CT 5. Chest CT 6. Pelvic CT (if disease below waist) 7. Neck CT (if head and neck area) 8. Cranial MRI 9. CLND (if clinically positive inguinofemoral nodes)

Answer 33

Tx: Primary tumor cannot be assessed T1: ≤2 cm T2: >2 cm to ≤4 cm T3: >4cm T4: Invasion of adjoining structures - T4a: Tumor with orbital invasion, skull base/dural invasion, invasion of central compartment viscera, involvement of fascial skeleton, invasion of pterygoids - T4b: With brain parenchymal invasion, carotid artery encasement, prevertebral muscle invasion, or CNS involvement via perineural spread. N0: No regional LN or unknown LN status N1: Regional lymph node metastasis M0: No distant metastasis M1: Distant metastasis GX: Grade cannot be assessed G1: Total differentiation, mitotic count and necrosis score of 2 or 3 G2: Total differentiation, mitotic count and necrosis score of 4 or 5 G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8 Tumor Differentiation: 1: Sarcomas closely resembling normal adult mesenchymal tissue (e.g., lowgrade leiomyosarcoma) 2: Sarcomas for which histologic typing is certain (e.g., myxoid/round cell liposarcoma) 3: Embryonal and undifferentiated sarcomas, sarcomas of doubtful type, synovial sarcomas, soft tissue osteosarcoma, Ewing Sarcoma/primitive neuroectodermal tumor (PNET) of soft tissue Mitotic Count: 1: 0-9 mitoses per 10 HPF 2: 10-19 mitoses per 10 HPF 3: ≥20 mitoses per 10 HPF Tumor Necrosis 0: No necrosis 1: <50% tumor necrosis 2: ≥50% tumor necrosis STAGING Stage I (Low-grade) Stage IA: T1 N0 M0 G1,GX Stage IB: T2-T4 N0 M0 G1,GX ``` Stage II (Mod-high grade, ≤2 cm) Stage II: T1 N0 M0 G2,G3 ``` Stage III (Mod-high grade, >2cm) Stage IIIA: T2 N0 M0 G2,G3 Stage IIIB: T3-T4 N0 MO G2,G3 Stage IV (Concurrent Mets) Any T N1 M0 Any G Any T Any N M1 Any G

Answer 34

``` Tx: Primary tumor cannot be assessed T1: ≤5 cm T2: >5 cm to ≤10 cm T3: >10 cm to ≤15 cm T4: >15 cm ``` N0: No regional LN or unknown LN status N1: Regional lymph node metastasis M0: No distant metastasis M1: Distant metastasis GX: Grade cannot be assessed G1: Total differentiation, mitotic count and necrosis score of 2 or 3 G2: Total differentiation, mitotic count and necrosis score of 4 or 5 G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8 Tumor Differentiation: 1: Sarcomas closely resembling normal adult mesenchymal tissue (e.g., lowgrade leiomyosarcoma) 2: Sarcomas for which histologic typing is certain (e.g., myxoid/round cell liposarcoma) 3: Embryonal and undifferentiated sarcomas, sarcomas of doubtful type, synovial sarcomas, soft tissue osteosarcoma, Ewing Sarcoma/primitive neuroectodermal tumor (PNET) of soft tissue Mitotic Count: 1: 0-9 mitoses per 10 HPF 2: 10-19 mitoses per 10 HPF 3: ≥20 mitoses per 10 HPF Tumor Necrosis 0: No necrosis 1: <50% tumor necrosis 2: ≥50% tumor necrosis STAGING Stage I (Low-grade) Stage IA: T1 N0 M0 G1,GX Stage IB: T2-T4 N0 M0 G1,GX ``` Stage II (Mod-high grade, ≤5 cm) Stage II: T1 N0 M0 G2,G3 ``` Stage III (Mod-high grade, >5cm) Stage IIIA: T2 N0 M0 G2,G3 Stage IIIB: T3-T4 N0 MO G2,G3 Stage IV (Concurrent Mets) Any T N1 M0 Any G Any T Any N M1 Any G

Answer 35

Tx: Primary tumor cannot be assessed T1: Organ confined T2: Tumor extension into tissue beyond organ - T2a: Invades serosa or visceral peritoneum - T2b: Extension beyond serosa (mesentery) T3: Invades another organ T4: Multifocal involvement - T4a: Multifocal (2 sites) - T4b: Multifocal (3-5 sites) - T4c: Multifocal (>5 sites) N0: No regional LN or unknown LN status N1: Regional lymph node metastasis M0: No distant metastasis M1: Distant metastasis GX: Grade cannot be assessed G1: Total differentiation, mitotic count and necrosis score of 2 or 3 G2: Total differentiation, mitotic count and necrosis score of 4 or 5 G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8 Tumor Differentiation: 1: Sarcomas closely resembling normal adult mesenchymal tissue (e.g., lowgrade leiomyosarcoma) 2: Sarcomas for which histologic typing is certain (e.g., myxoid/round cell liposarcoma) 3: Embryonal and undifferentiated sarcomas, sarcomas of doubtful type, synovial sarcomas, soft tissue osteosarcoma, Ewing Sarcoma/primitive neuroectodermal tumor (PNET) of soft tissue Mitotic Count: 1: 0-9 mitoses per 10 HPF 2: 10-19 mitoses per 10 HPF 3: ≥20 mitoses per 10 HPF Tumor Necrosis 0: No necrosis 1: <50% tumor necrosis 2: ≥50% tumor necrosis

Answer 36

``` Tx: Primary tumor cannot be assessed T0: No evidence of primary tumor T1: ≤2 cm T2: >2 cm to ≤5 cm T3: >5 cm to ≤10 cm T4: >10 cm ``` N0: No regional LN or unknown LN status N1: Regional lymph node metastasis M0: No distant metastasis M1: Distant metastasis Grading for GIST is based on mitotic rate Low: ≤5 mitoses per 5mm^2, or per 50hpf High: >5 mitoses per 5mm^2, or per 50hpf Staging Gastric GIST (Also: Omentum) Stage IA: T1-T2 N0 M0, Low MR Stage IB: T3 N0 M0, Low MR Stage II: T1-T2 N0 M0, High MR T4 N0 M0, Low MR Stage IIIA: T3 N0 M0, High MR Stage IIIB: T4 N0 M0, High MR Stage IV: Any T, N1 M0, Any MR Any T, Any N, M1, Any MR Small Intestinal GIST (Also: Esophagus, colorectal, mesenteric, peritoneal) Stage I: T1-T2 N0 M0, Low MR Stage II: T3 N0 M0, Low MR Stage IIIA: T1 N0 M0, High MR T4 N0 M0, Low MR Stage IIIB: T2-T4 N0 M0, High MR Stage IV: Any T, N1 M0, Any rate Any T, Any N, M1, Any rate

Answer 37

``` Tx: Primary tumor cannot be assessed T1: ≤5 cm T2: >5 cm to ≤10 cm T3: >10 cm to ≤15 cm T4: >15 cm ``` N0: No regional LN or unknown LN status N1: Regional lymph node metastasis M0: No distant metastasis M1: Distant metastasis GX: Grade cannot be assessed G1: Total differentiation, mitotic count and necrosis score of 2 or 3 G2: Total differentiation, mitotic count and necrosis score of 4 or 5 G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8 Tumor Differentiation: 1: Sarcomas closely resembling normal adult mesenchymal tissue (e.g., lowgrade leiomyosarcoma) 2: Sarcomas for which histologic typing is certain (e.g., myxoid/round cell liposarcoma) 3: Embryonal and undifferentiated sarcomas, sarcomas of doubtful type, synovial sarcomas, soft tissue osteosarcoma, Ewing Sarcoma/primitive neuroectodermal tumor (PNET) of soft tissue Mitotic Count: 1: 0-9 mitoses per 10 HPF 2: 10-19 mitoses per 10 HPF 3: ≥20 mitoses per 10 HPF Tumor Necrosis 0: No necrosis 1: <50% tumor necrosis 2: ≥50% tumor necrosis STAGING Stage I (Low-grade) Stage IA: T1 N0 M0 G1,GX Stage IB: T2-T4 N0 M0 G1,GX ``` Stage II (Mod-high grade, ≤5 cm) Stage II: T1 N0 M0 G2,G3 ``` Stage III (Mod-high grade, >5cm) Stage IIIA: T2 N0 M0 G2,G3 Stage IIIB: T3-T4 N0 MO G2,G3 Stage IV (Concurrent Mets) Any T N1 M0 Any G Any T Any N M1 Any G

Answer 38

Environmental sources of radiation damage are typically from UV radiation. UVC rays are filtered by the ozone layer, so the only UV rays that humans typically encounter are UVA (320–400 nm) and UVB (290–320 nm). The amount of exposure to UV radiation is dependent on seasonal, temporal, geographic and environmental variables. Ninety-five percent of the UV rays that reach the earth’s surface are UVA rays. This radiation is less energetic (longer wavelength) than UVB rays and affects the cutaneous tissues differently. UVA waves penetrate deeper into the tissues, with 20% to 30% reaching the deep dermis. UVB rays are mostly absorbed in the epidermis, with 70% reaching the stratum corneum, 20% reaching the deep epidermis, and only 10% reaching the papillary dermis. Major chromophores in the cutaneous tissue include nucleic acids, aromatic amino acids, and melanin.

Answer 39

The short-term effects of solar radiation include erythema and pigmentation. The resultant erythema peaks at 6 to 24 hours after exposure. The pigmentation occurs differently for UVA and UVB rays. Pigmentation occurs because of photooxidation of melanin by UVA radiation. Partial fading of this pigment change occurs within an hour after exposure, but with higher and repeated doses of UVA, stable residual pigmentation is observed. UVB waves induce neomelanization, increasing the total amount of melanin in the epidermal tissues and resulting in an effect that is observable 72 hours after exposure. The increase in melanin as a result of UVB exposure serves as a protective mechanism to defend the nuclei of the basal keratinocytes from further radiation-induced damage by absorbing the high-energy radiation in future exposures.

Answer 40

Long-term effects of exposure to UV radiation can lead to chronic skin changes, such as irregular pigmentation, melasma, postinflammatory pigmentation, and actinic lentigines (sun spots). Lysozyme, an enzyme secreted by cells of the immune system, typically inhibits the activity of collagenase and elastase, playing a role in turnover of the elastin and collagen network of the dermis. Long-term exposure to UV radiation increases the activity of lysozyme, thus impairing the natural turnover of these fibers, resulting in a disorganized accumulation of elastin, and an increase in the ratio of type III to type I collagen. This results in loss of firmness and resilience of the skin, leading to wrinkles and an aged appearance.

Answer 41

The various forms of radiation work to destroy the replicative potential of the target cells via damage to the nucleic acid structures in the cell. This is typically used to treat oncologic disease, but it can also be used to treat benign disease like eczema, psoriasis, and keloid scarring at relatively low exposures. While this goal is accomplished, surrounding tissues are also affected and damaged. The most radiosensitive components of the cutaneous tissue are the basal keratinocytes, hair follicle stem cells, and melanocytes. Exposure to this intense radiation results in disorganized, uncontrolled cell death, leading to the release of reactive oxygen species and further damage and inflammation to the surrounding cellular network. Damage to the basal keratinocytes and fibroblasts hinders the replicative capacity of the epidermis and dermis, respectively. Acute skin changes to these structures manifest within weeks as erythema, edema, and alopecia. Permanent hyperpigmentation, tightening, thickening, and fibrosis of the skin become apparent as the tissue attempts to heal. In severe radiation injury, there can be complete loss of the epidermis, resulting in partial-thickness wounds and fibrinous exudate. Reepithelialization typically occurs 14 days following initial injury, provided other variables affecting wound healing are optimized (bacterial colonization, nutrition.) Long-term effects include compromise of the functional integrity of the skin secondary to thrombosis and necrosis of capillaries, hypovascularity, telangiectasia, ulceration, fibrosis, poor wound healing, and infection. These can present weeks to years after exposure.

Answer 42

Treatment of minor radiation injury includes skin moisturizers and local wound care when appropriate. Severe radiation injury may warrant surgical excision and reconstruction with free-tissue transfer from a part of the body unaffected by radiation.

Answer 43

Amoxicillin/Clavulanate x 3-7 days Alternatives: Doxycycline or Clindamycin with Ciprofloxacin

Answer 44

TX: Primary tumor thickness cannot be assessed (diagnosis by curettage) T0: No evidence of primary tumor Tis: Melanoma in situ T1: ≤1 mm, unknown/unspecified - T1a <0.8mm, without ulceration - T1b <0.8mm, with ulceration 0. 8-1.0mm, with/without ulceration T2: >1.0–2.0mm, unknown/unspecified - T2a >1.0–2.0mm, without ulceration - T2b >1.0–2.0mm, with ulceration T3: >2.0-4.0mm, unknown/unspecified - T3a >2.0-4.0mm without ulceration - T3b >2.0-4.0mm with ulceration T4: >4.0mm, unknown/unspecified - T4a >4.0mm, without ulceration - T4b >4.0mm, with ulceration NX: Regional nodes not assessed (SLNB not done, LN previously removed) *Exception: when there are no clinically detected regional mets in a pT1 cM0 melanoma, assign cN0 instead of pNX N0: No regional mets detected N1: One tumor involved node, or in-transit, satellite and/or microsatellite mets with no tumor-involved nodes) - N1a one clinically occult (ie, by SLN biopsy) - N1b one clinically detected - N1c No regional lymph node disease (+in-transit, satellite and/or microsatellite metastases) N2: Two or three tumor-involved nodes, or in-transit, satellite, and/or microsatellite metastases with one tumor-involved node - N2a Two or three clinically occult (ie by SLN biopsy) - N2b Two or three, at least one of which was clinically detected - N2c One clinically occult or clinically detected (+in-transit, satellite and/or microsatellite metastases) N3: Four or more tumor-involved nodes or in-transit, satellite, and/or microsatellite metastases with two or more tumor-involved nodes, or any number of matted nodes without or with in-transit, satellite, and/or microsatellite metastases - N3a Four or more clinically occult (ie, detected by SLN biopsy) - N3b Four or more, at least one of which was clinically detected, or presence of any number of matted nodes - N3c Two or more clinically occult or clinically detected and/or presence of any number of matted nodes (+in-transit, satellite and/or microsatellite metastases) M0: No evidence of distant mets M1: Evidence of distant mets - M1a Distant mets to skin, soft tissue including muscle, and/or nonregional lymph node - -M1a (0) Normal LDH - -M1a (1) Elevated LDH - M1b Distant metastasis to lung with or without M1a sites of disease - -M1b (0) Normal LDH - -M1b (1) Elevated LDH - M1c Distant metastasis to non-CNS visceral sites with or without M1a or M1b sites of disease - -M1c (0) Normal LDH - -M1c (1) Elevated - M1d Distant metastasis to CNS with or without M1a, M1b, or M1c sites of disease - -M1d (0) Normal LDH - -M1d (1) Elevated LDH Stage 0: Tis N0 M0 ``` Localized Disease with No Evidence of Metastases: Stage IA: T1a N0 M0 Stage IB: T1b-T2a N0 M0 Stage IIA: T2b-T3a N0 M0 Stage IIB: T3b-T4a N0 M0 Stage IIC: T4b N0 M0 ``` Regional Disease Stage III: Any T, Tis ≥N1 M0 Distant Metastatic Disease Stage IV: Any T, Any N, M1

Answer 45

GENETIC 1. Skin type 2. Personal history of prior melanoma 3. Multiple atypical/dysplastic nevi 4. Positive family history of melanoma 5. Inherited genetic mutations ENVIRONMENTAL 1. Excess sun exposure 2. UV-based artificial tanning

Answer 46

1. Overall tumor thickness 2. Mitotic rate 3. Ulceration

Answer 47

Patients presenting with a suspicious pigmented lesion optimally should undergo an excisional biopsy (elliptical, punch or saucerization), preferably with 1- to 3-mm negative margins. The orientation of the excisional biopsy should always be planned with definitive treatment in mind (eg, a longitudinal orientation in the extremities, parallel to lymphatics). With the increasing use of lymphatic mapping and sentinel node biopsy, biopsies should also be planned so as not to interfere with this procedure. In this regard, wider margins for the initial diagnostic procedure should be avoided. For other sensitive/aesthetic sites, or very large lesions, a full-thickness incisional or punch biopsy of the clinically thickest portion is acceptable. If inadequate initial biopsy, a re-biopsy with narrow margin excision should be done. For low-suspicion settings, a shave biopsy may be acceptable.

Answer 48

1. Clinical node status (palpable vs. nonpalpable) | 2. Number of metastatic nodes

Answer 49

In-transit metastasis is defined as intralymphatic tumor in skin or subcutaneous tissue more than 2 cm from the primary tumor but not beyond the nearest regional lymph node basin. The presence of microsatellites, clinically evident satellites, and/or regional intransit disease is all part of the biologic continuum of regional lymphatic involvement, and these are all associated with a prognosis similar to that of patients with clinically positive nodes. This is recognized in the staging system with the designation of stage IIIC.

Answer 50

Among patients with distant metastatic melanoma (stage IV), the site of metastases is the most significant predictor of outcome. The three risk categories recognized by the AJCC are skin, soft tissue, and remote nodes (M1a); visceral-pulmonary (M1b); and visceral-nonpulmonary (M1c). Elevated lactate dehydrogenase (LDH), likely a surrogate for overall tumor burden, is also an independent predictor of poor outcome in patients with stage IV disease and has been incorporated into the AJCC staging system; patients with distant metastases to any site and elevated LDH are in the highest risk category (M1c).

Answer 51

After the diagnosis of cutaneous melanoma has been confirmed, detailed personal and family history, including any personal history of prior melanoma or dysplastic nevi, should be obtained. In the physical examination of patients with invasive melanoma, physicians should pay special attention to the locoregional area and lymph node drainage basin(s) of the established melanoma. A complete dermatologic examination is recommended for all patients with newly diagnosed melanoma.

Answer 52

* Stage 0 (melanoma in situ); or stage IA or IB with thickness 0.75 mm or less, regardless of other features (eg, ulceration, mitotic rate) * Stage IA with thickness 0.76 to 1.0 mm, with no ulceration, and mitotic rate 0 per mm2 * Stage IB with thickness 0.76 to 1.0 mm with ulceration or mitotic rate greater than or equal to 1 per mm2; or stage IB or II with thickness 1.0 mm thick, any feature (eg, with or without ulceration, any mitotic rate), and clinically negative nodes * Stage III with clinically detected (palpable) positive nodes, microscopic satellitosis (from assessment of the primary lesion), and/or in-transit disease * Stage IV (distant metastatic disease)

Answer 53

SLNB is almost always performed at the time of initial wide excision; the validity of performing this technique after definitive wide excision has not been extensively studied. There is at least a theoretical concern that the relevant draining lymphatics could have been disturbed by the wide excision, especially if rotation flaps or skin grafts were used for reconstruction, degrading the accuracy of the SLNB procedure. The technique for SLNB consists of: 1) preoperative dynamic lymphoscintigraphy, 2) intraoperative identification using isosulfan blue or methylene blue dye, and 3) a gamma probe to detect radiolabeled lymph nodes.

Answer 54

1) Wound dehiscence & infection 2) Seroma/hematoma 3) Lymphedema

Answer 55

1) T2 and higher (>1-4mm depth) 2) Thin melanoma with adverse features (>0.75mm, >1 mitosis per mm, ulcerated) SLNB provides prognostic info and is therapeutic for low volume disease. The incidence of regional mets increases significantly: <1mm = ≤5% >4mm = 35-40% And also, there is at least a 10% risk of clinically occult nodal metastasis.

Answer 56

Stage 0, I, II 1) PE of primary site, regional lymphatic pathways, lymph node basin, and skin. 2) Nodal basin UTZ for equivocal regional PE prior to SLNB. 3) SLNB: The NCCN Melanoma Panel does not recommend SLNB for patients with in situ melanoma (stage 0). For patients with stage IA melanomas that are 0.76 to 1.0 mm thick without ulceration, and with mitotic rate 0 per mm2, SLNB should be considered in the appropriate clinical context. SLNB should generally be discussed and offered for patients with higher- risk stage IB (>1 mm thick or 0.76–1.0 mm thick with ulceration or mitotic rate ≥1 per mm2) or stage II melanoma. 3) Wide-excision alone (in general).

Answer 57

Stage III Sentinel Node-Positive 1) Cross-sectional imaging as warranted by symptoms. Clinically Node-Positive 1) Confirm suspicion with FNA, or core/incisional/excisional biopsy for enlarged lymph nodes. If non-diagnostic, excisional biopsy, planned with therapeutic LN dissection in mind, is appropriate. In-Transit Nodes 1) Confirm suspicion with FNA, or core/incisional/excisional biopsy for enlarged lymph nodes. If non-diagnostic, excisional biopsy, planned with therapeutic LN dissection in mind, is appropriate. 2) Cross-sectional imaging as warranted by symptoms. SLNB may be considered for patients with resectable solitary in-transit stage III disease (category 2B recommendation). However, while SLNB may be a useful staging tool, its impact on the OS of these patients remains unclear. Since patients with stage IIIC have an appreciable risk of symptomatic CNS recurrence, and symptomatic CNS metastasis are associated with significant morbidity and poor survival, baseline CNS imaging should be considered in these high-risk patients.

Answer 58

1) Confirm suspicion of stage IV metastatic disease with FNA or CNB, incisional, excisional biopsy of the metastases. 2) Genetic analyses (BRAF or KIT mutation status are appropriate for patients being considered for treatment with targeted therapy, or if mutational status is relevant to eligibility for participation in a clinical trial. To ensure that adequate metastatic material is available for mutational analysis, biopsy (core, excisional, or incisional) is preferred if initial therapy is to be systemic and archival tissue is not available. However, the panel also recognized that brain metastases are typically treated without histologic confirmation. 3) Baseline chest/abdominal/pelvic CT. 4) Because patients with metastatic melanoma have a high incidence of brain metastases, brain MRI or CT scan with contrast should be performed at presentation with stage IV disease. Brain MRI is also recommended if patients have even minimal symptoms or physical findings suggestive of CNS involvement, or if results of imaging would affect decisions about treatment. 5) Serum LDH

Answer 59

In-situ (Tis) 0.5 to 1cm margin (+ layer of subcutaneous tissue) ``` Melanomas ≤1.0mm thick (T1) 1cm margin (+ layer of subcutaneous tissue) ``` Melanomas 1.01 to 2mm thick (T2) 1-2cm margin Melanomas >2mm thick (T3 & T4) 2cm margins 1- to 2-cm margins might be acceptable in anatomically difficult areas where a full 2-cm margin would be difficult to achieve. Depth is up to superficial fascia, but not through deep fascia. For sole of the foot, excise down to the plantar fascia.

Answer 60

If the sentinel node is negative, regional lymph node dissection is not indicated. For patients with stage III disease based on a positive SLN, a CLND of the involved nodal basin should be discussed and offered, in the context of all of the points raised above, including the probability of a positive NSLN, the prognostic value of the NSLN status, the morbidity of the procedure, and the fact that one prospective randomized controlled trial has shown no benefit in any clinically relevant endpoint. The impact of CLND on plans for adjuvant therapy or clinical trial enrollment should also be considered. Patients presenting with clinically positive nodes without radiologic evidence of distant metastases should undergo wide excision of the primary site (if present) and CLND of the involved nodal basin. In the setting of inguinal lymphadenopathy, a pelvic dissection is recommended if the PET/CT or pelvic CT scan reveals iliac and/or obturator lymph node involvement (category 2A) or if a positive Cloquet’s lymph node is found on intraoperative frozen section (category 2B). Pelvic dissection also should be considered for clinically positive inguinal-femoral nodes or if three or more inguinofemoral nodes are involved (category 2B). For primary lesions in the head and neck with clinically or microscopically positive lymph nodes in the parotid gland, a superficial parotidectomy alone is insufficient and the panel recommends appropriate neck dissection of the draining nodal basins.

Answer 61

Most patients with in situ or early-stage melanoma will be cured by primary excision alone. However, patients with desmoplastic melanomas, especially those with extensive neurotropism, are at high risk for local recurrence, especially if margins are suboptimal. Adjuvant radiation following surgery may be considered to improve local control. Adjuvant RT may be considered for select patients with clinically positive nodes and features predicting a high risk of nodal basin relapse.

Answer 62

Adjuvant treatment outside of a clinical trial is not recommended for patients with stage I/II disease, although the rationale for this recommendation varies across the NCCN Panel. There are no FDA- approved adjuvant immune checkpoint inhibitors or BRAF-targeted therapies for this group of patients. Although most of the trials to date did not include patients with stage I/II disease (Table 5), clinical trials are underway to define the role of adjuvant checkpoint inhibitors in high-risk stage II patients. For patients with resected advanced melanoma, there have been a number of prospective randomized trials suggesting that immune checkpoint inhibitor and BRAF-targeted therapy are effective options for adjuvant treatment. The most important factor to consider is the risk of recurrence and/or death from disease. Stage IIIA is the lowest risk group for which the NCCN Guidelines recommend considering adjuvant treatment.

Answer 63

Treatment in the context of a clinical trial is the preferred option for in- transit disease. For those with a single or a small number of resectable in- transit metastases, complete surgical excision with histologically negative margins is preferred, if feasible. In the patient undergoing curative resection of a solitary in-transit metastasis, SLNB can be considered (category 2B).

Answer 64

For limited metastatic disease, options include resection, if feasible, or systemic therapy. Observation is no longer a recommended option, even for patients with very limited stage IV disease, now that there are more effective active treatment options available. Systemic treatment should be followed by repeat scans to rule out the possibility that the disease is not more widespread, and to better select patients for surgical intervention.

Answer 65

Disseminated disease can be managed by one or more of the following options, depending on the location of and extent of metastatic disease: clinical trial, systemic therapy, local treatment, or best supportive care (see the NCCN Guidelines for Palliative Care). For all systemic therapy options, consult the prescribing information for dosing recommendations. A number of options are available for systemic therapy. For extracranial metastases, local treatment options may include intralesional injection with T-VEC, resection, or radiation. T-VEC can be injected into nodal or distant metastases to help with disease control, but the impact on survival is not known. It may be useful for patients with very limited stage IV disease, or in combination with other treatment modalities. Symptomatic extracranial metastases can be managed with palliative resection and/or radiation. Radiation can be used for palliation of visceral, bone, and CNS metastases. Recommendations for First-line Systemic Therapy For first-line therapy of unresectable or distant metastatic disease, recommended treatment options include immune checkpoint inhibitors, BRAF-targeted therapy for patients with an activating BRAF V600 mutation, or clinical trial. Immune checkpoint inhibitor options in this setting include anti-PD-1 monotherapy with pembrolizumab (category 1) or nivolumab (category 1) or nivolumab/ipilimumab combination therapy (category 1). Immune checkpoint inhibitors have been shown to be effective regardless of BRAF mutation status. The NCCN Panel considers all recommended immune checkpoint inhibitor options appropriate for both BRAF mutant and BRAF wild-type metastatic disease.

Answer 66

Persistent Disease or Local Scar Recurrence The panel recognized the distinction between true local scar recurrence after inadequate initial excision (which most likely represents locally persistent disease) and local recurrence after adequate initial excision, (which likely represents dermal lymphatic disease appearing in proximity to the wide excision scar).732 In the former situation, defined by the presence of in situ and/or radial growth phase, the prognosis after re-excision is related to the microstaging of the recurrence, whereas the latter scenario is prognostically similar to recurrent regional disease. For persistent disease or true local scar recurrence after inadequate primary therapy, a biopsy is required for confirmation. Guidelines for this biopsy should be the same as for primary tumors. The workup should be similar to that of the primary tumor based on microstaging characteristics. Re-excision to appropriate margins is recommended, with or without lymphatic mapping and SLNB according to primary tumor characteristics. Adjuvant treatment should be based on pathologic stage of the recurrence, and should be similar to that of primary tumors of equivalent stage.

Answer 67

Initial clinical recurrence should be confirmed pathologically whenever possible or if clinically indicated. Pathology should be confirmed by FNA cytology, if feasible, or core, incisional, or excisional biopsy. Local or satellite recurrences are in the deep dermis or subcutaneous fat within the melanoma scar or satellite metastasis adjacent to the melanoma scar. By definition they are recurrences after initial adequate wide excision, and lack in situ or radial growth phase. Tissue from the recurrence (preferred) or archival tissue should be assessed for mutation status if the patient is being considered for targeted therapy or enrollment in a clinical trial that includes mutation status as an eligibility criterion. Baseline imaging (CT and/or PET/CT or MRI) is recommended for staging and to evaluate specific signs or symptoms (category 2B). Options for treatment of unresectable local, satellite, or in-transit recurrences include intralesional injection with T-VEC, ILP or ILIwith melphalan, or systemic therapy (as recommended for metastatic disease). The following are category 2B alternatives: intralesional injections with BCG, IFN alfa, or IL-2, topical imiquimod (for superficial dermal lesions), local ablation therapy, or RT. After complete response to any of these modalities, options include participation in a clinical trial or observation. For those rendered free of disease by surgery, an additional adjuvant therapy option is high-dose IFN alfa (category 2B).

Answer 68

For patients presenting with regional nodal recurrence, the clinical diagnosis should be confirmed by FNA (preferred) or core, incisional, or excisional biopsy. Tissue from the recurrence (preferred) or archival tissue should be assessed for mutation status if the patient is being considered for targeted therapy or enrollment in a clinical trial that includes mutation status as an eligibility criterion. Baseline imaging (CT and/or PET/CT or MRI) is recommended for staging and to evaluate specific signs or symptoms (category 2B). For patients who have not undergone prior lymph node dissection or had an incomplete lymph node dissection, a CLND is advised. If the patient underwent a previous CLND, excision of the recurrence to negative margins is recommended if possible. After complete resection of nodal recurrence, options for adjuvant treatment include a clinical trial, observation, or, in patients who were not previously treated, high-dose or pegylated IFN alfa, high-dose ipilimumab (category 2B), or biochemotherapy (category 2B). Adjuvant radiation to the nodal basin may also be considered in selected high-risk patients based on size, location, and number of involved nodes, and/or macroscopic extranodal extension (category 2B). For patients with incompletely resected nodal recurrence, unresectable disease, or systemic disease, options include systemic therapy (preferred), clinical trial, palliative RT, intralesional injection with T- VEC, or best supportive care (see NCCN Guidelines for Palliative Care).

Answer 69

For patients presenting with distant recurrence, the workup and treatment options are similar to those outlined previously for patients presenting initially with stage IV metastatic disease.

Answer 70

GENES - Sonic hedgehog signaling pathway (PTCH1 gene on chromosome 9q-- underlying cause of nevoid BCC syndrome, and are present in 30-90% of sporadic BCCs. - UV-induced mutations in the tumor suppressor gene p53. GENETIC SYNDROMES - Albinism (absent skin pigment) - Xeroderma pigmentosum (defects exist in UV light-induced unscheduled DNA repair)

Answer 71

On clinical presentation of the patient with a suspicious lesion, workup for BCC begins with a history and physical examination, with an emphasis on a complete skin examination. A full skin examination is recommended, because individuals with a skin cancer often have additional, concurrent precancers or cancers located at other, usually sun-exposed skin sites. These individuals are also at increased risk of developing cutaneous melanoma. A skin biopsy is then performed on any suspicious lesion. The biopsy should include deep reticular dermis if the lesion is suspected to be more than a superficial process. This procedure is preferred because an infiltrative histology may sometimes be present only at the deeper, advancing margins of a tumor, and superficial biopsies will frequently miss this component. Imaging studies should be performed when extensive disease, such as bone involvement, perineural invasion, or deep soft tissue involvement, is suspected. MRI is preferred over CT scan if perineural disease is suspected because of its higher sensitivity.

Answer 72

LOW RISK - Trunk and extremities (except hands, nail units, pretibia, ankles, feet) <20mm - Cheeks, forehead, scalp, neck pretibia <10mm - Well-defined borders - Primary tumor - Not immunocompromised - No site of prior RT - Nodular, superficial - No perineural involvement

Answer 73

HIGH RISK - Trunk and extremities (except hands, nail units, pretibia, ankles, feet) ≥20 mm - Cheeks, forehead, scalp, neck pretibia ≥10mm - Mask areas of face (central, eyelids, eyebrows, periorbital, nose, lips, chin, mandible, preauricular, postauricular skin/sulci, temple, ear, genitalia, hands, feet - Poorly defined borders - Recurrent - Immunosuppression - (+) site of prior RT - Aggressive growth pattern - (+) perineural involvement

Answer 74

Basal cell carcinoma (80% of all skin cancers)

Answer 75

``` Nodular BCC (60%) - Classic domed, pearly papule with surface telangiectasia (rodent ulcer) ```

Answer 76

1) Surgical excision with postoperative margin assessment (>98% 5-year disease-free rates) - Low-risk (well-circumscribed, <2cm): 4mm clinical margins 2) Mohs Micrographic Surgery or Excision with Intraoperative Frozen Section Assessment - Preferred for high-risk BCC - Intraop analysis of 100% of excision margin - Alternative: Excision with Complete Circumferential Peripheral and Deep Margin Assessment (CCPDMA) 3) Curettage and Electrodessication - For low-risk tumors except areas with terminal hair growth (tumor may extend down follicular structures) - Alternately scraping away tumor tissue with a curette down to a firm layer of normal dermis and denaturing the area by electrodessication. - Up to 3 cycles may be performed in a session. - No histologic margin assessment. - If subcutaneous layer is reached during C&E, do surgical excision. 4) Radiation Therapy - For unresectable tumors, inferior cosmesis; advised only for >60 years old because of concerns about long-term sequelae. - Contraindications: Genetic conditions predisposing to cancer and connective tissue diseases 5) Superficial Therapies a. Topical (Imiquimod + 5-FU) - Superficial BCC <2cm in non-immunocompromised patient - 5days/week x 6 weeks (clearance rate >80%) b. Cryosurgery - Destroys tumor cells by freeze-thaw cycles - Poorer cosmetic outcomes c. Photodynamic Therapy - Application of photosensitizing agent on skin followed by irradiation with a light source - Methyl aminolevulinate (MAL) and 5-aminolevulinic acid (ALA) - For premalignant or superficial low risk lesions on any location on the body. In patients with superficial BCC, - PDT has similar efficacy as cryotherapy but much better cosmetic outcomes; and - PDT, imiquimod, and fluorouracil have similar efficacy and cosmetic outcomes, although risk of recurrence may be somewhat higher with PDT versus imiquimod. 6) Intralesional Interferon - Intralesional interferon alfa-2b can be effective for treating low-risk, superficial BCC

Answer 77

NCCN Recommendations: 1) LOW-RISK BCC - C&E in areas without hair growth - Standard excision if lesion can be excised with a 4mm clinical margins and with closure techniques such as linear closure, secondary intention, or skin graft - RT for non-surgical candidates limited to those >60 years old. - If margins are positive after excision, patients should receive adjuvant therapy. MMS, resection with CCPDMA with frozen or permanent section, or standard re-excision for area L regions (trunk and extremities, excluding pretibia, hands, feet, nail units, and ankle) are recommended, while radiation may be administered to non-surgical candidates. 2) HIGH-RISK BCC - Standard excision using wider margins with linear or delayed repair, with standard re-excision - MMS or resection with CCPDMA - RT for non-surgical candidates Patients treated with MMS or resection with CCPDMA should receive adjuvant therapy if clear margins cannot be achieved. Recommended adjuvant therapy options include radiation and/or multidisciplinary consultation to consider systemic therapy with a hedgehog pathway inhibitor or treatment in the context of a clinical trial (vismodegib/ sonidegib). Adjuvant RT is also recommended for patients with negative margins after surgery but with large nerve or extensive perineural involvement. Due to the potential for skull involvement and intracranial extension, an MRI should be considered if large-nerve invasion is suspected for tumors on the head and neck. If negative margins are not achieved after standard excision, patients should undergo MMS or resection with CCPDMA, or receive adjuvant RT. If residual disease is still present after adjuvant treatment, and further surgery and RT are contraindicated, clinicians should consider multidisciplinary consultation to determine whether the patient should be offered systemic treatment with a hedgehog pathway inhibitor or treatment in the context of a clinical trial.

Answer 78

For the management of local tumor recurrence, the algorithm directs clinicians to follow the appropriate pathways for primary treatment. Although the behavior of cutaneous BCC is characteristically indolent, the disease does occasionally metastasize to distant sites. Whenever possible, nodal or distant metastases should be treated with surgery with or without RT, and managed by a multidisciplinary tumor board. The board should consider systemic therapy with a hedgehog pathway inhibitor or treatment in the context of a clinical trial. FDA-approved hedgehog pathway inhibitors include vismodegib and sonidegib.

Answer 79

The frequency of follow-up should be based on risk. In addition to patient education about sun protection and self-examination, patients should be monitored with regular physical exams including complete skin examination. Monitoring during the first 2 years is the most critical, and exams should occur at least every 6 to 12 months during this timeframe. If no further skin cancer develops in the first 2 years, then it may be appropriate to reduce exam frequency.

Answer 80

TX: Primary tumor cannot be assessed Tis: Carcinoma in situ T1: Tumor smaller than or equal to 2 cm in greatest dimension T2: Tumor larger than 2 cm, but smaller than or equal to 4 cm in greatest dimension T3: Tumor larger than 4 cm in maximum dimension or minor bone erosion or perineural invasion or deep invasion* T4: Tumor with gross cortical bone/marrow, skull base invasion and/or skull base foramen invasion - T4a Tumor with gross cortical bone/marrow invasion - T4b Tumor with skull base invasion and/or skull base foramen involvement *Deep invasion is defined as invasion beyond the subcutaneous fat or >6 mm (as measured from the granular layer of adjacent normal epidermis to the base of the tumor); perineural invasion for T3 classification is defined as tumor cells within the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in caliber, or presenting with clinical or radiographic involvement of named nerves without skull base invasion or transgression. Clinical N NX: Regional lymph nodes cannot be assessed N0: No regional lymph node metastasis N1: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(−) N2: Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(−); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(−); or in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(−) - N2a Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(−) - N2b Metastases in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension and ENE(−) - N2c Metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(−) N3: Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(−); or metastasis in any node(s) and clinically overt ENE [ENE(+)] - N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(−) - N3b Metastasis in any node(s) and ENE (+) M0: No distant metastasis M1: Distant metastasis GX: Grade cannot be assessed G1: Well differentiated G2: Moderately differentiated G3: Poorly differentiated G4 Undifferentiated ``` Stage 0: Tis N0 M0 Stage I: T1 N0 M0 Stage II: T2 N0 M0 Stage III: T3 N0 M0 T1-3 N1 M0 Stage IV: T1-3 N2 M0 Any T, N3, M0 T4, Any N, M0 Any T, Any N, M1 ```

Answer 81

1) Sun exposure/tanning 2) Scars or chronic wounds/trauma/burns (Marjolin ulcer) 3) Actinic keratoses (sun-induced precancerous lesions) 4) Bowen's disease (SCC in situ) 5) Genetic syndromes: Albinism, xeroderma pigmentosum 6) Immunosuppression

Answer 82

1) Hx and PE, complete skin and regional LN exam (also at increased risk for other cancers such as melanoma) 2) Biopsy (include deep reticular dermis) 3) Imaging studies when extensive disease is suspected. MRI with contrast is preferred over CT if perineural disease or deep soft tissue involvement is suspected. If bone disease is expected, CT with contrast is preferred unless contraindicated. 4) Palpable LN should prompt an FNA or core biopsy. 5) Risk stratification of the primary tumor to determine treatment plan and follow up.

Answer 83

LOW RISK - trunk and extremities (excluding hands, nail units, pretibia, ankles, and feet) <20mm - cheeks, forehead, scalp, neck, and pretibia <10mm - Well-defined borders - Primary tumor - No immunosuppression - No previous RT site/inflammation - Slow growing tumor - No neurologic symptoms - Well or mod differentiated - Not any of these: Acantholytic (adenoid), adenosquamous (showing mucin production), desmoplastic, or metaplastic (carcinosarcomatous) subtypes - ≤6 mm and no invasion beyond subcutaneous fat - No perineural, lymphatic or vascular involvement HIGH-RISK - trunk and extremities (excluding hands, nail units, pretibia, ankles, and feet) ≥20mm - cheeks, forehead, scalp, neck, and pretibia ≥10mm - “mask areas” of face (central face, eyelids, eyebrows, periorbital, nose, lips [cutaneous and vermilion], chin, mandible, preauricular and postauricular skin/sulci, temple, and ear), genitalia, hands, and feet - Poorly- defined borders - Recurrent tumor - (+) Immunosuppression - (+) previous RT site/inflammation - Rapidly growing tumor - (+) Neurologic symptoms - Poorly differentiated - (+) Acantholytic (adenoid), adenosquamous (showing mucin production), desmoplastic, or metaplastic (carcinosarcomatous) subtypes - >6 mm or with (+) invasion beyond subcutaneous fat - (+) Perineural, lymphatic or vascular involvement

Answer 84

LOW-RISK 1) C&E in areas without hair growth (ie, excluding terminal hair-bearing regions, such as the scalp, pubic and axillary regions, and beard area in men), provided that the treatment be changed to excision if the adipose tissue is reached; 2) standard excision if the lesion can be excised with 4mm (<2cm lesions) to 6-mm (>2cm lesions) clinical margins and repaired with linear closure, secondary intention healing, or skin graft; and 3) RT for non-surgical candidates, generally limited to those older than 60 years of age because of risk of long-term toxicity. If margins are positive after excision, patients should receive additional therapy. MMS, resection with CCPDMA with frozen or permanent section, or standard re-excision for area L regions (trunk and extremities, excluding pretibia, hands, feet, nail units, and ankle) are recommended, while radiation may be administered to non-surgical candidates. ``` HIGH-RISK 1) standard excision, using wider margins with linear or delayed repair; (4mm for <1cm; 6mm for 1-1.9cm; 9mm for >2cm) ``` 2) MMS or resection with CCPDMA with frozen or permanent section; and 3) RT for non- surgical candidates. Similarly, patients treated with MMS or resection with CCPDMA as first- line therapy should receive subsequent therapy if clear margins cannot be achieved. Recommended options include radiation (of primary site) and/or multidisciplinary consultation to consider chemoradiation or clinical trial. Appropriate chemotherapy agents can be found in the NCCN Guidelines for Head and Neck Cancers. If invasion into parotid fascia is discovered during MMS or resection with CCPDMA, then superficial parotidectomy is indicated. Adjuvant RT to the primary site is recommended for patients with negative margins after surgery if there is large nerve or extensive perineural involvement. Due to the potential for skull involvement and intracranial extension, an MRI with contrast of the area of interest should be considered if large-nerve invasion is suspected for tumors on the head and neck. For certain high-risk SCCs, SLNB mapping may be considered. A systematic review of 692 patients with SCC reported positive sentinel nodes in 24% and 21% of anogenital and non-anogenital patients, respectively.240 The survival benefit of and indication for SLNB remains unclear.

Answer 85

1) Keratoacanthomas - can mimic SCC/BCC - grow rapidly & involute - still warrant biopsy. 2) Actinic (Solar) Keratosis and Cutaneous Horns - Premalignant lesions in sun-exposed areas of fair-skinned patients - High risk of developing multiple primary cSCCs. - Atypical clinical appearance or lack of response to therapy warrants biopsy. - Tx options: - -- Topical 5-FU - -- Topical Imiquimod - -- Topical Ingenol mebutate - -- PDT - -- Cryotherapy - -- C&E 3) Actinic keratosis on the lip (Actinic cheilitis) - Tx options: - -- Ablative laser vermillionectomy 4) Bowen Disease - Slow growing erythematous plaque with scaling or crusting surface - Sun exposure, immunosuppression, HIV - Cutaneous SCC in situ - 10% progress to invasive SCC - Tx: Complete excision with negative margins. 5) Dysplastic Nevi - Increased risk to develop MELANOMA. - Red-brown, scalloped edges, variegated pigmentation, >6mm - Trunk, non-exposed areas.

Answer 86

Merkel cell carcinoma - Cutaneous neuroendocrine tumor from the neuroectoderm - Rapidly-growing, pink to red-blue violaceous firm nodule, in elderly patients - Associated with POLYOMA Virus - Tx: 1) Wide excision with histologic confirmation of negative margins - - <2cm tumor = 1cm margin - - >2cm tumor = 2cm margin - LV invasion is a major prognostic factor. - Poor overall survival (50-80% mort) with high recurrence. 2) For clinically node-negative MCC: Do SLNB with selective LN dissection! 3) Adjuvant radiotherapy improves locoregional control (fairly radio/chemosensitive tumor) IHC: - Pancytokeratin AEI/AE3 - Cytokeratin 20 - Chromogranin A

Answer 87

Dermatofibrosarcoma protuberans - Rare, low-grade malignant CA of dermis - Most common DERMAL Sarcoma - Nodular, plaque-like, violaceous - Slow-growing, trunk and proximal extremities - Middle-aged adults - High local recurrence rates, but minimal metastatic potential. - Dx: Punch biopsy (spindle cells in dermis with storiform architecture, decreased mitotic rate, with fingerlike extensions at the border) - IHC: CD-34 expression. - Tx: Wide excision with 3-5cm margins that are pathologically negative. - Other tx options: 1) Imatinib: Only for shown chromose 17-22 translocation 2) RT: Only for UNRESECTABLE disease/close margins.

Answer 88

Tx: Neutralize inciting solution in saline/distilled H2O! ACIDIC Solution: 30mins ALKALINE Solution: 2hours

Answer 89

1) Topical/locally injected calcium gluconate (binds fluoride ions) 2) Topical calcium carbonate gel + quaternary ammonium compounds (detoxifies fluoride ions)

Answer 90

1) Zone of coagulation - EPICENTER of injury 2) Zone of stasis - Most amenable to salvage - Marginal perfusion, questionable viability 3) Zone of hyperemia

Answer 91

ACTINOMYCOSIS - most common: cervicofacial form - acute pyogenic infection in submandibular or paramandibular area - should be considered in any acute, subacute or chronic cutaneous swelling of the H&N - can spread beyond boundaries of tissue planes, may mimic chronic osteomyelitis - Tx: PENICILLIN + Surgical debridement

Answer 92

Treat with Beta-lactam antibotics (+MRSA Coverage if no response) for nonpurulent, complicated cellulitis

Answer 93

Kaposi Sarcoma - After 5th decade of life - Mostly in skin - HIV & transplant patients - Multifocal rubbery blue nodules - Tx: - --AIDS associated Kaposi Sarcoma: Antiviral - -- Cryotherapy, photodynamic tx, radiation tx, topical, intralesional - -- Surgery is reserved for PALLIATION.

Answer 94

Hidradenitis Suppurativa - Chronic inflammatory disease presenting as painful subcutaneous nodules (atrophy of sebaceous gland followed by inflammation of pilosebaceous unit causing hyperkeratosis and granuloma formation) - Foul-smelling exudate RISK FACTORS - 3rd decade of life - Smoking and obesity - Genetic predisposition exacerbated by environmental factors (gamma-secretase gene mutation) STAGES (HURLEY) 1: Single/multiple nodules or abscesses W/O sinus tracts or scarring 2: Abscesses recur and WITH sinus tract and scarring 3: Diffuse disease and interconnected sinus tracts and abscesses - Tx: Stage I/II: Clindamycin Advanced Stage II/III: Radical excision, laser treatment, biologic agents Topical antimicrobial creams and grafts, flaps and secondary intention healing are advised. - Prognosis: High recurrence rates up to 50%

Answer 95

TEN - Autoimmune reaction to stimuli resulting in structural defects at the epidermal-dermal junction - Follow a prodromal period similar to URTI - Symmetrical macular eruption: face--> trunk--> extremities - Nikolsky sign: Lateral pressure causes epidermis to detach from basal layer. - Blisters form as extensive SPT injury with exposed dermis - Tx: Withdraw drug, supportive care, IVIG

Answer 96

TBSA Involved: <10%: SJS >30%: TEN 10-30%: SJS-TENS

Answer 97

- Rare adenocarcinoma of the apocrine glands (perianal, axillary, genitalia) - Eczema-like appearance - High incidence of concomittant other malignancies. - Tx: Resection to negative margins and adjuvant RT.

Answer 98

Stage I: Nonblanching erythema over intact skin Stage II: Partial-thickness injury (epidermis/dermis) with blister/crater Stage III: Full-thickness injury extending down to but not including fascia and without undermining adjacent tissue Stage IV: Full-thickness skin injury with destruction/necrosis of muscle, bone, tendon, or joint capsule. Tissue pressures that exceed pressure of the microcirculation (30mmHg) cause tissue ischemia. Muscle is more suspectible to ischemia than skin (increased metabolic demand): ``` Areas at Risk: Ischial tuberosity 28% Trochanter 19% Sacrum 17% Heel 9% ```

Answer 99

``` TYPES I: 80% are polymicrobial - Most common pathogens: --Bacteroides fragilis --Eschericia coli ``` II: Group A beta-hemolytic strep III: Gram negative marine organisms (most common is VIBRIO VULNIFICUS) Tx: Broad spectrum antibiotics and surgical debridement LRINEC Score: 1) WBC count 2) Hgb 3) CRP 4) Glucose 5) Creatinine 6) Na+

Answer 100

EPIDERMAL INCLUSION CYST - Most common - Completely mature epidermis + granular layer - Creamy material: Keratin from desquamated cells TRICHILEMMAL CYST - Scalp, no granular layer - Females GANGLIONS - Connective tissue from synovial membrane of a joint/tendon sheath - 60% on dorsal wrist, region of scapholunate ligament - Tx: For asymptomatic px, just ASPIRATE. For failed aspiration, EXCISE. DERMOID CYST - Along body fusion planes - Midline abdomen/sacrum, occiput, nose, bone/tooth/nerve tissue. - Congenital, with squamous epithelium, eccrine glands, pilosebaceous units PILONIDAL CUST - Acquired - From embedded hairs in the intergluteal cleft - MALES > F (2-4x risk)

Answer 101

NF1 is Von Recklinghausen Disease. - Autosomal dominant - NF1 gene on chromosome 17q11.2 encodes neurofibromin protein (neuroectodermal differentiation, cardiac development) ``` DIAGNOSIS ≥2 OF 8: 1) Cafe au lait spots ≥6 > 5mm (for <10yo) >15mm (for adults) ``` 2) Neurofibromas (≥2) - MOST COMMON (3-15% lifetime risk for malignancy) 3) Axillary/inguinal freckling 4) Lisch nodules (≥2 iris hamartomas) 5) Optic nerve gliomas 6) Sphenoid dysplastic/long bone abnormalities 7) Cutaneous, subcutaneous, visceral NF 8) 1st deg relative with NF - PET Scan differentiates benign from malignant tumors.

Answer 102

Type I and III collagen

Answer 103

d. Excisional biopsy

Answer 104

c. wide excision

Answer 105

b. Stage II malignant melanoma

Answer 106

E. Malignant fibrous histiocytoma

Answer 107

A. Vimentin Vimentin: intermediate cytoplasmic filament, immunoperoxidase staining sarcomas mark with antibody to vimentin. NSE: with neural differentiation Cytokeratin: epithelial origin (eg carcinomas) Factor VIII: Endothelial related CD3: T lymphocytic marker

Answer 108

B. Liposarcoma NODULAR FASCIITIS reactive fibroblastic lesion of young adults, usually on the upper extremities and trunk, can develop several weeks after trauma LIPOSARCOMA located in deep soft tissues and can be indolent; large size; most common sarcomas of adulthood OSTEOSARCOMA Younger than 20 years old; typically arise in the metaphysis RHABDOMYOSARCOMA Children, most often a tumor of head and neck, genitourinary, or retroperitoneum HEMANGIOMA In extremities, they tend to be small circumscribed skin lesions CHONDROSARCOMA Seen over a wide age range, but arise within bone

Answer 109

D. Presence of epidermis covered by an external basal layer. EPIDERMAL Most common type of cutaneous cyst, and may present as a single, firm nodule anywhere on the body; have a mature epidermis complete with a granular layer Substance is actually KERATIN Cyst walls consist of an epidermal layer oriented with the basal layer superficial, and the more mature layers deep (ie, with epidermis growing into the center of the cyst) The desquamated cells (keratin) collect in the center to form the cyst. DERMOID Congenital lesions that result when epithelium is trapped during fetal midline closure Eyebrow is most frequent site of presentation, but dermoid cysts are common anywhere from nasal tip to forehead Demonstrate squamous epithelium, eccrine glands, ilosebaceous units May develop bone, tooth, or nerve tissue on occasion. TRICHELEMMAL AKA Pilar cysts, the second most common cutaneous cyst, occur more often on the scalp of females Cyst walls do NOT contain a granular layer Contain a distinctive outer layer resembling the root sheath of a hair follicle (trichilemmoma)

Answer 110

D. Nodular

Answer 111

C. Lentigo maligna

Answer 112

A. Radiation therapy Stage I (Low-grade tumors): Surgical resection Stage II (≤5cm, high-grade tumors): Surgery +/- RT Stage III (>5cm, high-grade or nodal disease): Surgery, RT +/- Chemotherapy Stage IV (Distant metastatic disease): Chemotherapy +/- Surgery Small (<5cm) primary tumors with no evidence of distant mets are managed with local therapy consisting of surgery, alone or in combination with RT, when wide pathologic margins are limited because of anatomic constraints.

Answer 113

D. Synovial sarcoma HIGH SENSITIVITY TO CHEMO: Synovial sarcoma Myxoid/round cell ``` INTERMEDIATE SENSITIVITY TO CHEMO: Liposarcoma Myxofibrosarcoma MPNST Angiosarcoma Desmoplastic Round cell ``` POOR SENSITIVITY (RESISTANT) TO CHEMO: GIST Chondrosarcoma

Answer 114

A. Local resection with 3cm margin of normal tissue Lymphatic spread is NOT the primary route of mets for GI sarcomas. Lymphadenectomy is not routinely performed as part of resection. General recommendation is to perform a margin-negative resection with 2-4cm margins of normal tissue.

Answer 115

B Actinic (solar) keratosis is the most common premalignant lesion usually seen in older, light- complexioned individuals. The incidence of degeneration to invasive squamous carcinoma is 20–25%. These carcinomas, arising from actinic keratosis, metastasize suggesting conservative excision in treating them.

Answer 116

C Bowen’s disease represents an intraepithelial squamous cell carcinoma (carcinoma in situ) and is seen in older patients. These lesions tend to have a long clinical course. Adequate excision is the recommended treatment as these lesions can become invasive squamous cell carcinomas and metastatasize.

Answer 117

(A) Basal cell carcinoma is the most common malignancy in caucasians. The lesion is cured by complete excision and reconstruction (Moh’s) surgery.

Answer 118

E Wound contraction refers to the decrease in diameter of an open wound. It commences on about the fourth day after injury and continues at a relatively rapid rate (1/2–1 mm/d). It is maximal in areas where tissue laxity exists. Wound contraction should not be confused with wound contracture where scar formation over a joint interferes with mobility. Experimentally, it less affected by excision of tissue from the center of the wound, rather than at the periphery.

Answer 119

D Following the application of a full-thickness graft, contraction at the site of the recipient site is maximally inhibited by a full-thickness and to a lesser extent by the partial-thickness graft.

Answer 120

A The ileostomy should be circular rather than square to avoid excessive stenosis of the stoma. Wound healing by a square incision results in a greater degree of stenosis than by an equivalent circular stoma. Failure to close the gap between the ileal loop on the abdominal wall may lead to subsequent internal herniation. It is critical to ensure that the ileal stump is not devascularized.

Answer 121

C In a clean wound, the anticipated infection rate should be 1.5–5%, in a contaminated wound, 15%, and a dirty wound, 30–40%.

Answer 122

A If spillage is substantial or infected tissue has entered, the wound is classified as contaminated. Dirty wounds are used for drainage of an abscess or debridement of infected tissue.

Answer 123

D In a second-degree burn, the skin appendages in the dermis are minimally destroyed (superficial partial thickness) or more extensively destroyed (deep partial thickness). In a third-degree (full-thickness) burn, all of the dermis, with skin appendages, are destroyed, and the lesion extends to the subcutaneous fat layer.

Answer 124

D In calculating burn surface area, the rule of “9’s” assigns 9% to each upper extremity, 18% to each lower extremity, and 9% to the head and neck. The trunk and abdomen (36%) is divided into four equal parts (9% each). Thus, upper trunk anteriorly would be 9%.

Answer 125

A Continue with increased amount of lactated Ringer solution. Urine flow should be 0.5–1.0 mL/kg/h. Patients exposed to inhalation on burns, and those admitted following alcoholic intoxication require additional fluids. In general, for second- and third-degree burns, the Parkland formula is used to administer 4 mL/kg weight of patient × percentage of area of burn. Half of the calculated amount is given within 8 hours and the remainder during the subsequent 16 hours.

Answer 126

C Use cadaver allograft when required. Tangential excision of the skin (to secure a bleeding surface) is done with a guarded dermatome. However, because of possible extensive blood loss, it should be limited to an area <20% of the total body surface area. The presence of bacteria growth >105 organisms/cm2 or growth of beta-hemolytic streptococci should contraindicate split-skin-thickness grafting.

Answer 127

C It is inherited as a autosomal dominant disorder and noted in nearly 1/5000 births. The NF-1 gene encodes a protein neurofibromin that plays a role in neuroectodermal differentiation and cardiac development.

Answer 128

C Most melanoma arise from nondysplastic nevi. Congenital nevocellular nevi found in about 1/100 births have a 3–5% lifetime risk of undergoing malignant change. Dysplastic (atypical) nevi may be familial and predisposed to malignancy. Hutchinson freckle occurs mainly in older patients.

Answer 129

A The surface of a basal cell carcinoma has a shiny appearance with telangiectasia. Ulcer formation may occur; hence, are named rodent ulcer. Although treatments with 5 FU, cryosurgery, or electrodessication are effective in treatment, surgical excision offers the best results and ensures an accurate diagnosis.

Answer 130

A ``` Level II (≤0.75mm) involves the papillary dermis (T1); Level III (0.76-1.5mm) between the papillary and reticular dermis (T2); Level IV (1.51-4mm) the reticular dermis (T3); and Level V (≥4mm) the subcutaneous fat (T4). ``` The Breslow classification utilizes differences in the thickness of the tumor.

Answer 131

E Usually caused by staphylococci and streptococci. Hidradenitis suppurativa is an infection of the apocrine glands and surrounding subcutaneous tissue and fascia, which most commonly involves the axilla, groin, perineum, and perianal region. The periumbilical and areola region may be involved. In milder cases, local hygienic measures and tetracycline may be adequate; in more severe cases, wide excision is indicated.

Answer 132

C The stratum corneum consists mainly of dead cells and keratin.

Answer 133

C It is inherited as a autosomal dominant disorder and noted in nearly 1/5,000 births. The NF-1 gene encodes a protein neurofibromin that plays a role in neuroectodermal differentiation and cardiac development.

Answer 134

E Gorlin’s syndrome is genetically determined, a disorder of childhood onset. Along with multiple basal cell carcinomas, other abnormalities include skin ribs on the palms and soles, epithelial jaw line cysts, rib abnormalities, ectopic calcifictions in the dura, and mental retardation. The disease is transmitted as autosomal dominant with no sex linkage. Generally the tumors have a benign clinical course until after puberty.

Answer 135

B. Lymphoma

Answer 136

A. Retroperitoneal leiomyosarcomas usually metastasize to the liver.

Answer 137

C. They generally present as large masses usually >20cm at time of diagnosis

Skin and Soft Tissue Flashcards

(163 cards)