Tumor biology Flashcards

Question

What is this structure ? - Presentation - Location ? - Structure ? - Difference from trichilemmal cyst ? - Treatment ?

Answer 1

Proliferating Trichilemmal cyst/tumor: - Presents as slow growing firm dermal nodule with smooth surface. - 90% on scalp; usually in elderly women. - Structure is same as trichilemmal cyst (Isthmic follicular epithelium/ORS). - Difference from trichilemmal cyst: 1. More proliferative centrally. 2. Areas of multicystic architecture. - Treatment is complete excision (recommended, benign tumor).

Answer 2

**Dermoid cyst**: - Presents in infants (most commonly lateral eyebrow) - Due to entrapment of epidermis during embryogenesis. -**Originate from Ectoderm**. -Lined by stratified squamous epithelium WITH granular layer. -Contains lamellated keratin in the center with adnexal structure. - Caution: do not biopsy until cranial connection is excluded.

Answer 3

Vellus Hair Cysts: - AD - Presents as multiple eruptive domed and flesh colored or hyperpigmented papules. - Location: trunk. - Structure: Follicular infundibular epithelium with vellus hair in center (same as epidermal cyst). - Lined by stratified squamous epithelium WITH granular layer. -Contains lamellated keratin in center with vellus hair.

Answer 4

**Steatocytoma**: - Presents as single or multiplex (AD) -Location: trunk -Lined by stratified squamous epithelium WITH granular layer. -Eosinophilic cuticle (Shark tooth) sebaceous glands in walls. - **Multiplex Related to Pachonychia Congenita 2 "Keratin 6b/17".**

Answer 5

**Hidrocystoma**: -**Most common on FACE.** -Presents as translucent bluish cysts. -Structure is unilocular or multilocular cyst lined by layers of epithelial cells and luminal decapitation secretion, cyst appears empty. -**Associated with Schopf-Schulz-Passarge: - AR, WNT10A gene on ch2. - Presents with multiple hidrocystomas, syringofibroadenomas, PPK, hypodontia, and hypotrichosis.**

Answer 6

**Bronchogenic Cyst** -Presents as solitary cyst from birth at suprasternal notch/Anterior neck. -**Structure: Lined by pseudostratified ciliated columnar epithelium with GOBLET CELLS.** -**Cyst lining often surrounded by smooth muscle, mucous glands, cartilage, or lymphoid follicles**.

Answer 7

Thyroglossal cyst: - Presents as solitary mid anterior neck cyst. - Structure: lined by cuboidal, columnar, or stratified squamous epithelium, may contain some ciliated columnar cells. - Characteristic thyroid follicles in cyst wall.

Answer 8

Median raphe cyst on ventral penis

Answer 9

Branchial Cleft Cyst: - Structure: Stratified Squamous epithelium or pseudostratified ciliated columnar epithelium. -Has abundant lymphoid tissue. -Next step is MRI or CT before removal.

Answer 10

Omphalomesenteric duct cyst

Answer 11

-**Digital Mucous Cyst (Pseudocyst)**. - **Myxoid cyst not lined by epidermis.**

Answer 12

1. Congenital (Mongolian Spot) 2. Nevus of Ota 3. Nevus of Ito - They are caused by shorter wavelengths reflected by melanocytes.

Answer 13

Mongolian Spots: - Presents at birth in most as gray blue patch. - Lumbosacral region. - Histologically: dermal melanocytes are distinguished from blue nevi by their decreased cellularity and lack of dermal sclerosis. - Treatment: often resolves during childhood.

Answer 14

Nevus of Ota: - Presents in 1st year of life or around puberty. - Presents as coalescing Grey/Blue macules in V1/V2 distribution, unilateral in 90%, and frequent scleral involvement. - Most common extra cutaneous sites: Sclera > tympanum. - Persists for life. - May enlarge under hormonal influences. - 10% develop glaucoma. - Rare malignant degeneration to uveal melanoma higher risk with activating mutations in GNAQ.

Answer 15

Nevus of Ito located on the shoulder.

Answer 16

- Blue Nevus - Caused by melanocyte in dermis (rather than epidermis); onset in childhood/adolscence. - **Activating mutation in GNAQ & GNA11 (Most Common)**. -Most common melanoma to this mutation is **uvula melanoma**. - Carney complex: related to epitheloid blue nevi & multiple blue nevi. - Histology: more sclerosis and cellularity and dermal dendritic melanocytes.

Answer 17

- **Kamino bodies** (pink clumps of BMZ material COL4) within epidermis (PAS+ globules). - The lesion is Spitz nevus. - **Its dermoscopy shows starburst finding in pigmented variants**. - Acquired solitary lesions in first two decades "dome shaped red-brown or tan pink smooth surfaced papules" located on head and neck. - Pathogenisis is HRAS mutation/11p gains. - Immunostains (S100A6+, p16+); P16 is frequently lost/diminished in atypical spitz tumors and spitzoid melanoma. - Treatment: complete excision recommended. - Homozygous loss of 9p21 "risk of metastasis and death" ;atypical epithelioid nevi associated with loss of BAP-1. Mnemonic: someone with kamino (Violin) spitz and HRAS the audience.

Answer 18

-**Halo Nevus** -**Multiple are related to Infliximab**. -**Histology will show Lichenoid infiltrate among nested melanocytes with pigment incontinence**.

Answer 19

**Congenital Melanocytic Nevus:** - NRAS mutation - Can be small or large >20 cm. - **Large congenital melanocytic nevus:** • If posterior axial congenital nevi multiple satellites: **Recommend MRI screening for neurocutaneous melanosis**. • Can affect various organ; CNS with high mortality. • Risk of Melanoma in 1st decade , **2-5% risk of melanoma (4%)** • Developed proliferative nodules like melanoma.

Answer 20

- Benign lesion. - Related to UV exposure > BRAF mutation. - Epidermolysis Bullosa

Answer 21

- Dysplastic/ Atypical Melanocytic Nevus. - Sporadic or familial - Located at any site (trunk and scalp most common. - Presents as asymmetric, irregularly bordered, and variably pigmented nevi ranging in size (often >6mm). -Treatment is to observe & severly atypical nevi should be re-excised. -Syndrome: • Familial Atypical Multiple Mole Melanoma Syndrome "FAMMM": 1. AD inheritence of CDKN2A gene (p16 & p14ARF) 2. Characterized by multiple melanocytic nevi (50+). 3. Family history of melanoma

Answer 22

Becker Melanosis (Not true melanocytic Disorder): - Presents as hyperpigmented plaque with thickening, irregularity, and or hypertrichosis on upper torso in young adults around puberty. - Poland syndrome: ipsilateral breast hypoplasia seen in some patients. - **Association:** 1. **Smooth Muscle Hamartoma, hypoplasia of underlying structures, such as unilateral breast hypoplasia, unilateral or ipsilateral pectoralis major aplasia, acneiform lesions, skeletal defects.** 2. **Increased smooth muscle in dermis.**

Answer 23

- Can be sporadic mutation or inherited. - Inherited mutations (Less common): • **CDKN2A mutations (P16, P14, RAF).** • **P16 mutation is also related to pancreatic tumors.** - Sporadic mutations (More common) : • **BRAF mutation (V600 is the most common mutation); associated with superficial spreading melanoma, Nonsunexposed skin.** • NRAS mutation: chronic sun exposure; Nodular melanoma. • **C-KIT mutation: chronic sun exposure; acral and mucosal melanoma**. • **GNAQ/GNA11 mutation: related to blue nevi cause Uvula melanoma.** - Aggressive tumor resulting from melanocytes and affecting younger population (20-45 yrs).

Answer 24

• Tendancy to sunburn/freckle. • Light colored skin/hair/eyes. • **Several Nevi**. • Inherited mutations (CDKN2A). • Aquired genetic mutations (BRAF). • Prior history of melanoma. • Intermittent high UVR with sunburns in childhood/Adolesence. • **Immunosuppression (Transplant patients 3-4 fold higher risk).**

Answer 25

1. Superficial Spreading Melanoma: - Most common (70% in whites). - Presents as darkly pigmented macule or thin plaque +/- notched border, varying shades of brown, and possible areas of regression. - **Most common site is back (men) & lower legs (Women)**. - Horizontal growth. 2. Nodular melanoma: - 2nd MC type in light skinned. - Darkly pigmented papule or nodule with rapid onset. - Located on head/neck. - Vertical growth. 3. Lentigo Maligna Melanoma: - Least common. - **Yet, MC in 70's age group**. - Evolves from lentigo maligna, often in **Sun-exposed sites** in older age group; presents as hyperpigmented patch with varying shades of brown, **irregular border**. 4. Acral Lentiginous Melanoma: - **Most common type seen in dark skinned patients**. - Hutchinson sign usually in advanced stage. - Often presents as hyperpigmented patch with varying shades of brown or black and irregular borders. • Intra-oral melanoma: - **The hard palate** (specifically the anterior palate/alveolar arch) is the highest risk location. • **Sclerosing Subtype is the most common to recur**. • Thick melanomas (>3mm) were predominantly **nodular** in type; they occurre in **older men**, mostly on **head and neck** and were associated with **fewer nevi**. • **Melanoma associated leukoderma:** hypomelanosis seen with melanoma most commonly may be seen in 3 ways: 1. Analogous to Halo nevus. 2. Remote leukoderma distant from primary site. 3. Vitiligo like leukoderma. • Melanoma associated leukoderma **may be associated with better prognosis**.

Answer 26

• Stains: - S100: most sensitive. - Melena A/HMP-45: specific (differentiate it from atypical melanocytic nevi). - SOX10: only in desmoplastic melanoma w/negative S100. • Stages: - Stage 1: <1mm depth (no ulceration). •Treatment: surgical. - Stage 2: >1mm depth (w/ ulceration). •Treatment: surgical. -Stage 3: positive LN. •Treatment: surgical + sentinel LN biopsy for intermediate thickness melanoma of **3-4mm**. -Stage 4: distant metastasis. •Treatment: add adjuvant therapy. - Melanoma thickness should be measured in millimeters from **top of granular cell layer of epidermis (or base of ulcer) to the deepest point of tumor penetration** using an ocular micrometer. - Recent guidelines have emphasized tumor mitotic rate (TMR) & have incorporated this into existing system.

Answer 27

- Dermoscopy: **Blue-White Veil**. - Histology: • assymetric, poorly-circumscribed collection of atypical melanocytes. • single melanocytes characteristic and often with pagetoid spread. • irregular nests in basal layer and invasion into dermis. • Poor maturation of melanocytes +/- regression. (know histology picture).

Answer 28

- Male gender. - Increasing age. - Increasing tumor thickness. - Ulceration. - Increased tumor mitotic rate. - head and neck and trunk locations (vs. extremities).

Answer 29

- Based on stage but its always surgical: • Conventional excision with margins • Mohs micrographic surgery • we perform +/- sentinel lymph node biopsy (Usually for intermediate thickness melanoma of 1-4mm). - For advanced cases: • Interferon-a • IL-2 • Chemotherapy/radiation therapy. • Vaccine therapy • Immunotherapy and targeted therapy (anti CLA4 antibody, anti-PD-1/PDL-1 antibody, MEK/BRAF inhibitors) **- BRAF inhibitors cause SCC/keratoacanthoma avoid this by adding MEK inhibitors.** -Vemurafinib: BRAF inhibitor>> causes multiple KAs due to **Paradoxical MAP kinase activation**. -**IFN-a, IL-2, TNF-a have all demonstrated to have some therapeutic benefit in treatment of melanoma; GM-CSFis the immune stimulator in the vaccine Talimogene Laherparepvec.** - Excision margins for melanoma: • **Melanoma-in-situ: 0.5cm margins**. • **Melanoma <2mm: 1cm margins** •Melanoma >=2mm: 2cm margins.

Answer 30

Trichofolliculoma (Adnexal tumor): - Origin is infundibulum - **Activation mutation of WNT encode B-Catenin in adult.**

Answer 31

Trichoepithelioma: - Arises from the infundibulum. - **Location:** Face MC on the **nose**. - Multiple seen in Brooke Spiegler syndrome & Rombo syndrome.

Answer 32

Fibrofolliculoma: - **Arises from the infundibulum of the hair follicle**. - **Related to Birt-Hogg-Dubé syndrome: AD, FLCN gene.** - **Birt-Hogg-Dubé is associated with Renal Cell Carcinoma** & medullary thyroid cancer.

Answer 33

Pilomatricoma (Calcifying epithelioma of Melhebre): - **Activation Mutation in CTNNB1 gene (encodes b-catenin, involved in WNT pathway)**. - **Multiple lesions** associated with: 1- **Turner Syndrome** 2- **Gardner Syndrome** 3- **Myotonic Dystrophy** 4- **Rubinstein-Taybi** Mnemonic: Ruby and turner are gardners that have weak muscles.

Answer 34

Trichilemmoma: - Origin: Isthmus - **Multiple tricholemmomas seen in Cowden syndrome: AD, PTEN mutation**.

Answer 35

Desmoplastic Trichoepithelioma: - **Location: on face (same as regular trichoepithelioma but later MC in nose)** - Histology: • Thinner cords of basaloid cells arrayed interstitially among dense collagenous stroma +- horn cysts +- calcium deposits. • **Presents as well-circumbscribed lesion in dermis.** - Note: histology resembles sclerosing BCC but benign lesion. - Helpful hint: it has a thumprint like shape in histology

Answer 36

Eccrine Poroma: - benign neoplasm from poroid eccrine duct. - Presents as solitary, vascular appearing papule/nodule may ulcerate or bleed. - Located in palms/soles > scalp. - Immunostain: CEA (Also EMA & PAS).

Answer 37

**Hidradenoma:** - **Benign neoplasm from the sweat glands APOCRINE > eccrine.** - Presents as solitary multilobulated nodule with a deep red/purple/**blue hue** and cystic quality, with serous discharge. - Malignant hidradenocarcinoma most common in head/neck.

Answer 38

**Syringoma:** - Presents as small transluscent skin colored papules often clustered over eyelids. - Located on periorbital region (eyelids). - **Histology with show** circumscribed proliferation of **small tadpole or comma shaped sweat ducts**. - Syndromes: 1. **Syringoma related to down syndrome**. 2. **Syringoma clear cell variant related to DM**. 3. **Eruptive syringomas (clinical variant):** 100s of hyperpigmented small papules over anterior trunk related to **down syndrome.**

Answer 39

Eccrine Spiradenoma: - Eccrine, benign presents as erythematous, blue or gray nodule +- Pain. - **On palpation it is painful.** - Histology will show: • Sharply-delineated basophilic nodule or nodules **(cannon balls or blue balls) in dermis. • **Solid lobules of basaloid cells composed of individual nodules of two cell types**; small dark basaloid cells in rosette pattern & pale large cells. - Eccrine spiradenoma, a basaloid adnexal lesion that exhibits apocrine differentiation.

Answer 40

Spiradenoma: - Benign apocrine neoplasm. - Presents as single painful dermal or subcutaneous nodule with blue-purple hue. - Lymphocytes peppered in tumor (classic finding); PAS +. - **Brooke-Spiegler Syndrome**: 1. **AD, CYLD mutation** 2. **Chromosome 16** 3. **Presents with spiradenomas, cylindromas** and also trichoblastomas, and trichoepitheliomas. - Increased risk of spiradenocarcinoma: CYLD (tumor suppressor) normally binds NEMO component of I-Kappa-B kinase (IKK) complex > inhibits NF'b mediated resistence to apopotosis.

Answer 41

**Cylindroma**: - Benign apocrine neoplasm that presents as single or multiple firm rubbery nodules with erythematous to blue color & telangectasia. - Location: scalp. - **Histology:** same as spiradenoma basaloid proliferation of discrete lobules but in **"Jigsaw" or Mosaic Pattern**. - **Multiple cylindromas** seen **with AD; CYLD mutation in Brooke-Spiegler Syndrome**. -**Cylindromas can be in association to Spiradenomas in Brooke-Spiegler Syndrome.** **Histology Picture Important**

Answer 42

Hidradenoma Papilliferum: - Presents as benign painless 1-2cm skin colored nodule. - Location: labia majora of young lady (almost always involving vulva). - Histology: Well circumscribed cystic proliferation in dermis with numerous **papillary projections with apocrine "Maze like" appearance**.

Answer 43

Syringocystadenoma Papilliferum: - Solitary, warty papule/plaque on scalp present in birth or early childhood. - **Associated with Nevus Sebaceous (HRAS mutation)**. -Histology: • exo-endophytic papillary glandular proliferation w/ "apocrine differentiation; opens into skin surface; abundant plasma cells."

Answer 44

**Microcystic Adnexal Carcinoma (Sclerosing Sweat Duct Carcinoma)**: - It is a locally aggressive sweat duct carcinoma occurs in middle aged adults. - Presents as indurated plaque resembling BCC. - **Location: perioral "Lip MC" > chin and cheek, perinasal, periorbital**. - Histology: sclerosing basaloid proliferation with bilineage differentiation (follicular & sweat), givong rise to proliferation of small sweat ducts and "follocular microcysts". -**Superficial biopsies of microcystic adnexal carcinoma are sometimes misdiagnosed for syringomas.** - **Another question showed a picture of tadpole to hint syringoma but the stem mentioned it is "very deep" >> think Microcystic Adnexal Carcinoma "MAC". - Treatment is by conventional excision or Mohs surgery; high recurrence rate. - Similar to desmoplastic trichoepithelioma "fingerprint histology" but MAC shows deep subcutaneous & perineural invasion; also MAC is CEA+. •**Note: both desmoplastic trichoepithelioma and MAC occur on face.** •**You may be shown histology and asked what does this tumor invade ? answer is NERVES.**

Answer 45

Extramammary Paget's Disease (EMPD): - Intraepthelial adenocarcinoma of apocrine gland; histologically and morphologically similar to paget's disease of the nipple. - Location: genital & perianal skin. - Presents as unilateral, well-demarcated erythematous plaque resembling chronic eczematous dermatitis in perianal or genital area; ensuing pruritis often results in excoriations & lichenification. - Histology: diffuse infiltration of large vacuolated cells with bluish cytoplasm (Paget cells) often in lower dermis. - CK20+ stains to differentiate it from pagetoid melanoma; **stains positive Cytokeratin 7**. - Treatment is thorough search for possible underlying malignancy & surgical excision.

Answer 46

Mucinous Carcinoma: - Rare adnexal tumor likely from eccrine gland. - Presents as slow-growing nodule, ulcer, or cyst with low metastatic potential. - Location: often in head or neck; **MC location for primary mucinous carcinoma is eyelid**. - Treatment: local excision; high rate of recurrence.

Answer 47

**Nevus Sebaceous:** - Benign hamartoma with follicular, apocrine, and sebaceous components. - Presents at birth along Blaschko's lines. - **HRAS Mutation**; and if extensive may be a/w **Schimmelpenning Syndrome**. - **Trichoblastoma & Syringocystadenoma Papilliferum** can arise from it. - Located on scalp/face most commonly can cause alopecia and becomes yellower and more verrucous after puberty. -Histology: • Lacks fully formed terminal hair. • Sebaceous glands open directly onto skin surface. • Dilated apocrine glands. **Know histology Picture**.

Answer 48

Sebaceous carcinoma: - Presents as erythematous pearly nodule or plaque. - **Often seen in peri-orabital "Pre-orbital" area (eyelid)**. - Histology: assymetric, poorly circumscribed lobules of basaloid or squamoid cells & poorly-developed atypical sebaceous cells (moderate to severe atypia). - Significant metastatic potential. - May be seen in Muir-Torre syndrome.

Answer 49

**Sebaceous hyperplasia:** - **Multiple yellow papules with central dell on face & upper trunk.** - **Stains with EMA.** - Most common sebaceous neoplasm is sebaceous Adenoma.

Answer 50

-**AD, MSH2 > MLH1> MSH6** and PMS2 mutations. - **Presents with multiple sebaceous neoplasms; multiple KAs; and risk of internal malignancy colon #1 & GU #2**.

Answer 51

Neurofibroma: - Benign proliferation of Schwann cells + other nerve components. - Plexiform neurofibroma (bag of worms) pathognomonic for NF1. - **Plexiform neurofibroma have highest potential to transform to Neurofibrosarcoma**. - **Rate of transformation: between 3/8-15% (10%)**. - Buttonhole sign positive: invagination when compressed by finger. - Stains positive with S100+ & neurofilaments. - Histology: • Proliferation in dermis consisting of spindle crlls with wavy nuclei. • Pale "bubblegum" stroma or fibromyxoid stroma, and mast cells. - Treatment if simple NF then simple excision.

Answer 52

Neuroma: tumor of neural tissue. - Presentation: solitary skin colored to erythematous firm papule associated with pain. - Types: 1. Traumatic neuroma: well-circumscribed nodule consisting of fascicles of peripheral nerve arranged on a haphazard pattern. 2. Palisaded Encapsulated Neuroma (PEN): well-demarcated proliferation of palisading spindle cells with encapsulation and fibrotic stroma.

Answer 53

- Tumor consisting of mature lipocytes and blood vessels. - Presents as soft subcutaneous nodules on forearms of young adults, often with pain. - Histology: Well-circumscribed neoplasm of mature adipose tissue with a variable number of small vessels +/- fibrin thrombi within vessels +/- mast cells.

Answer 54

**Merkel Cell Carcinoma:** - Aggresive malignant neoplasm. - **Origin is slow adaptive mechanoreceptors.** - Presents as red to pink dome-shaped ralidly growing nodule. - **Most common on head/neck** but can be seen in leg/buttock. - **Gene amplified is L-Myc.** - **Virus implicated is Polyomavirus** yields better prognosis. - Poor prognostic factors are: 1. Diameter >2cm. 2. P63 expression. • 5 year survival is only 40%.

Answer 55

- Histology: there are 3 histologic patterns: 1. Trabecular 2. Intermediate-cell type 3. Small-cell type • **Trabecular variant** consists of interconnecting trabecular separated by strands of connective tissue; **pseudorosettes may be seen**. - Immunohistochemic stain: • **CK20** (Perinuclear dot pattern). • Neurofilaments (Perinuclear dor pattern). • Chromogranin/Synaptophysin. • **Neuron Specific Enolase**. • EMA & CD56. - Negative stains are; TTF-1, CK7, **S-100**, & CEA. - **This neoplasm may contain several neuropeptides** including vasoactive intestinal peptide, calcitonin, **ACTH**, gastrin, and somostatin. - Histopathology: 1. speckled "salt & pepper chromatin" 2. Numerous mitosis and apoptotic cells. - **Treatment by Wide Local Excision (3cm margins) often with adjuvant chemotherapy and/or radiation, sentinel lymph node biopsy.**

Answer 56

Schwanomma (Neurilemmoma): - Benign nerve sheath tumor consisting of schwann cells. - 10% of cases are bilateral acoustic neuromas seen in NF-2 - Presents as painful subcutaneous skin-colored papulonodule often on extremity. - Immunostain: S100+, EMA, and negative neurofilaments -Histopathology: • Well circumscribed, encapsulated, deep dermal, consist of two areas: 1. Hypercellular (Antoni A): areas containing Verocay bodies (palisaded nuclei around acellular pink material). 2. Hypocellular (Antoni B): myxoid areas lack axons.

Answer 57

Neurothekoma: - Presents as red or brown papulonodule involving head; can be soft or firm. - Histology: well demarvated mass in reticular dermis or subcutaneous tissue containing myxoid nests or fascicles.

Answer 58

Angioleiomyoma: - benign tumors that originate from smooth muscle in vascular structures. - They are difficult to definitively diagnose clinically. - **Location:** althougg lesions rarely encountered in foot; lower extremity most common site **(leg)**. -

Answer 59

**Angiosarcoma:** - Very aggressive but rare tumor. - **Occurs more in caucasians than in non-caucasians; most often seen in elderly men.** - Presents as **Symptomatic** violaceous plaque on face on scalp; may be solitary or multiple. - **Location: MC on the scalp.** - Metastasis seen in lymph nodes, lungs, spleen, & liver; **Cervical LNs are most common site of mets.**

Answer 60

- Variants: 1. **Stewart-Treves Syndrome:** Angiosarcoma in presence of chronic lymphedema; **lymphedema resulting from radical mastectomy of breast cancer.** It is a late complication; 4-40 yrs **(>20).** 2. post Radiation: Most common on breast, arises after radiation therapy for breast cancer. - Histology: Poorly demarcated tumor cells consisting of dissecting vascular spaces with large pleomorphic hyperchromatic endothelial cells, extravasated red blood cells, **"Multilayered" or "Piled-on" architectire**. - Immunestain: • **CD31+, CD34+, Factor VIII related antigen +, and Cytokeratin +.** • **ERG +** (most sensitive and specific). • FLI-1+ • Radiation-induced angiosarcoma **( c-MYC amplification)**. - Poor prognosis. - Treatment with wide surgical excision but high rate of recurrence +/- adjuvant radiation therapy. Note: L-MYC in merkel cell, C-myc in radiation induced angiosarcoma.

Answer 61

**Infantile Hemangioma:** - Most common Vascular tumor; capillary proliferation that is GLUT-1 positive. - Timeline: 1. Usually not obvious at birth. 2. Rapid growth for 4-6 months. 3. Slow involution over years (5 years 50%, 9 years 90%) - Types: • Airway hemangioma: (Beard distribution). • Periorbital hemangioma: risk for astigmatism and ambylopia. - Variants (GLUT-1 negative): 1. Rapidly involuting infantile hemangioma (RICH): - Fully developed at birth. - No postnatal proliferation. - Involutes over 1 year. 2. Noninvoluting Infantile Hemangioma (NICH): - Fully developed at birth. - Growth proportionally with patient. - Does not involute. - Treatment for problematic lesions (ulceration, sensitive location): • B-blockers (1st line). • Corticosteroids. • Surgical or laser therapies.

Answer 62

**Pyogenic Granuloma (Lobular Capillary Hemangioma):** - Caused by: 1. Trauma 2. Pregnancy 3. **Medications: OCPs, Oral retinoids, INDINAVIR, & EGFR inhibitors**. - Presents most commonly in children & young adults as rapidly growing, exophytic, and hemorrhagic papule w/epidermal collarette. - Location: common sites are gingiva (pregnancy)/oral cavory, lips, and digits.

Answer 63

**Glomus tumor (Glomangioma):** - Benign tumor arise from the **nail bed.** - **Derived from Suquet-Hoyer Canal.** - Presents as solitary and painful lesion; commonly has **bluish-red discoloration** and may be tender or **painful** with exposure to hear or **cold**. - Histopathology: dense proliferation of glomus cells surrounding small vascular spaces. - Treatment: local surgical excision.

Answer 64

**Kaposi Sarcoma:** - **HHV-8 (present in 100%).** - Immunohistochemistry: LANA1 (100% sensitive/specific). - Presents as slow growing violaceous patches, plaques, or nodules. - Histology: **Dorf balls** are seen. - Variants: 1. Classic KS: Mediterranean, Ashkenazi Jewsish,; elderly males; initial lesion on distal extremity (may have disseminated involvement). 2. African endemic: in young patients with fulminant course. 3. AIDs-associated: single (trunk/midface) or disseminated. - Treatment: • Local cutaneous: antiretrovirals, intralesional chemotherapy Vinblastin. • Extensive cutaneous with involving lymph nodes or viscera; systemic chemotherapy Doxorubicin. **(Know Histology Picture)**

Answer 65

Granular Cell Tumor: - Presents often as solitary, skin colored to brown-red papulonodule often on head/neck. - Location: Tongue. - Histology: putulo-ovoid bodies if Milian (looks like an egg) , may see striated skeletal muscle lesion if on tongue.

Answer 66

- The MC cutaneous lymphoma (50%) affecting 70's and above. - Localized lesions mediated by TH1 response from peripheral memory T-cell, in tumor cell its TH2. - Defect in CD8 cytotoxic T-cell with release of interferon-gamma (Critical cause). - Types: 1. Patch stage: irregular erythematous scaly patchy, in non-sunexposed/bathing suit distribution, may be pruritic. 2. Plaque stage: well-demarcated variably shaped violaceous to red-brown plaques, may be pruritic. 2. Tumor stage: rapidly enlarging dome-shaped smooth nodules arising either de novo or from existing patches/plaques; aggressive with vertical growth. • Rare lymph node and visceral involvement. - **Poikilodermatous CTCL has an increased association with Lymphatoid Papulosis (Lyp)** compared to other types of mycosis fungoides. - **Erythrodermic Stage:** • ** T4 disease is defined as erythroderma with at at least 80% of skin surface disease**. • **The 80% of BSA is required for a patient to be classified as havinf CTCL lymphoma that qualifies as stage III-IVb; "Erythrodermic stage"**. Note: definition of erythroderma in general refers to 90% BSA such as in psoriasis or drug reaction.

Answer 67

- Investigation: 1. immunophenotype: • From T-helper cell (CD3+/CD4+/CD8-)** mature T-lymphocytes. • **CD45+.** • Variable loss of pan T-Cell markers: **CD7 loss is most common.** • **CD3+, CD4+, and CD45+, CD8- and CD7-**. 2. Histopathology: • In early stage (patch) not diagnostic so multiple biopsies are needed. •**Molecular testing for T-Cell receptor gene rearrangement for clonality.** • May need multiple biopsies before charactarestic changes seen; **atypical T cells negativr for CD7 T-cell marker**. - Environmental risk factors: • **HTLV (HIV) is associated with adult T cell lymphoma**. • MALT lymphomas ( Helicobacter pylori infections). • CBCL ( Borrelia Burgdorefi infections). • Enteropathy type T-cell lymphoma (Celiac disease). - Associated features with Post-transplant CTCL: • **Renal Transplant**. • **Cyclosporine**. • Tacrolimus. • Male sex.

Answer 68

• Treatment may be skin directed or systemic depending on stage. - Topical: corticosteroid or mechlorethamine (nitrogen mustard). - Phototherapy: PUVA, NBUVB. - Localized radiotherapy. - Electron beam therapy. - Photophoresis: typically for erythrodermic MF. - Immunosuppressants: methotrexate, interferon-a. - Bexarotene. - **Vornistat: Histone Deacetylase inhibitor**. - **Denileukon Diftitox:** • It binds selectively to the high and intermediate affinity **IL-2 receptor** (CD25+) on lymphocytes and is internalized by these cells. • The most frequent and clinical adverse event includes infusion reaction, **capillary leak syndrome** presenting as hypotension, Edema, pleural effusion, and fluid retention. - Chemotherapy. • Treatmenr summary: - Patch/Plaque stage: topical corticosteroids or ILCS, nitrogen mustard, phototherapy, and radiotherapy. - We can add interferon-alpha or retinoids for progressive disease. - Chemotherapy: reserved for advanced/ rapidly progressive disease; due to risk of secondary infections. •When staging lymphoma, it is critical to determine whether **the lymphoma is primary cutaneous** arising in the skin **or secondary cutaneous** arising in association with nodal or extra nodal tumor. • The prognosis is worse in secondary when compared to primary lymphomas irrespective of histologic diagnosis.

Answer 69

- Variants are: **1. Sezary syndrome:** - **Triad of lymphadenopathy, pruritic erythroderma, and Sezary cells (Large hyperconvoluted lymphocytes).** - Other symptoms include alopecia, nail dystrophy, oruritis, and scaling of palms and soles. - **TH2 response from central memory T-Cells**. - Disseminated condition: with sezary cells in skin, blood, lymph nodes, erythroderma, and lymphadenopathy. - **Blood: CD4+ neoplastic T-cells with an absolute count >1000 cells/uL. - **Diagnostic criteria**: 1) **Erythroderma (erythema >80% BSA).** 2) Clonal T-cell receptor rearrangement in blood. 3) Absolute Sezary T-Cell count of at least 1000 cells/uL OR one of the folowing two instead: • **Increased CD4+ T-Cells with a CD4 to CD8 ratio of >10:1**. • Increased CD4+ T-Cells with an abnormal phenotype (CD4+, CD7- or CD4+, CD26-). - **Sezary Syndrome has POOR PROGNOSIS**. **2. Folliculotriphic (Alopecia Mucinosa) 10%:** • Head/Neck area > Alopecia. • Involve follicular epithelium + follicular mucinosis. • More depth makes it more refractory to treatment. • **Worse Prognosis**. **3. Pagetoid Reticulosis (Woringer-Kolopp Disease):** • Progressive Solitary psoriasiform plaque on distal extremities. • **Mostly on hands and feet.** • Histology: very prominent epidermotropism in pagetoid pattern. • The infiltrate can be CD4+ or CD8+; unlike classic MF, **CD45 (leukocyte common antigen) tends to be negative.** •**Good prognosis**. **4. Granulomatous Slack Skin:** • extremely rare. • Sagging skin folds in axilla or groin; granulomatous inflammation with loss of elastic recoil. • Indolent course; usually evolved to classic MF; up to **30% develop Hodgkin's Lymphoma**. - **Syngotropic Mycosis Fungoides requires Punch biopsy for diagnosis**.

Answer 70

Review picture.

Answer 71

**Lymphatoid Papulosis (LyP):** - **CD30+ lymphoproliferative disorder, low grade malignancy.** - In adults 40s (vs Pityriasis Lichenoides Et Varioliformis Acuta favors children). - In up to 20% of patients, associated with another type of cutaneous malifnancy **Mycosis fungoides or Hodgkins' disease**; follow up required. - **Presents as recurrent xrops of papules that may ulcerate & spontaneously heal.** - Histology: 1. Type A: 75% wedge shaped infiltrate with clusters of large, atypical, **Reed-Steenberg like CD30+ (Ki-1) lymphocytes**. 2. Type B: same as patch/plaque stage MF. 3. Type C: same as Tumor Stage MF. 4. **Type D: CD4-/ CD8+/CD30+/ALK-**. • Note: All the rest type A, B, C are CD30+, CD3+, CD4+; **Type D is CD30+, CD3+, CD8+, CD4-, ALK-**. - Treatment: no curative benefit; low dose weekly methotrexate causes dramatic improvement (90%), PUVA, high potency corticosteroids, topical nitrogen mustard.

Answer 72

Cutaneous Leiomyoma: - Benign tumor presents as reddish brown, pink or skin-colored papules +/- pain. - Histology will **show interalcing bundles of cells with eosinophilic cytoplasm and no mitosis.** - **Desmin & SMA stains were positive.** - Cells contain elongated "Cigar-shaped nuclei". - **Reed's Syndrome:** • **Mutation in fumarate Hydratase**; which catalyzes conversion of fumarate to malate. • Multiple cutaneous and uterine leiomyomas. • **Increased risk of renal malignancy.**

Answer 73

Leiomyosarcoma: - Presents as superficial malignant smooth muscle tumor. - Excellent prognosis.

Answer 74

- This benign lesion **located on posterior shoulder or neck**. - Treatment is local excision.

Answer 75

**Myeloperoxidase**

Answer 76

**Low grade B cell Lymphomas.**

Answer 77

**BCL-2+, BCL-6+ (Most cases), and MUM-1+.**

Answer 78

A plantar Verrucous carcinoma that is locally aggressive but rarely metastasizes.

Answer 79

A plantar Verrucous carcinoma that is locally aggressive but rarely metastasizes.

Answer 80

**Oral Leukoplakia:** - A precancerous lesion. - Risk factors are **smoking, smokeless tobacco, alcohol, betel nut chewing**, weakened immune system,

Tumor biology Flashcards

(107 cards)