Clinical Flashcards
(283 cards)
1
Q
Benzene is assoc with:
A
AML
2
Q
TQ
Radiation may cause all leukemias except:
A
CLL
3
Q
TQ
Describe the chromosomal damage seen in CML.
What is the translocation?
What is the result?
A
CML:
- Philadelphia chromosome
- t (9 : 22)
- bcr joins abl»_space; new “fusion gene with tyrosine kinase activity
4
Q
t (15 : 17) is assoc with:
A
Acute Promyelocytic Leukemia (APL)
5
Q
In the acute leukemias (especially ALL) patients often complain of:
A
Bone pain
6
Q
Which leukemia, acute or chronic, is the dx often suspected on the basis of a CBC done as part of a routine workup for another problem?
A
Chronic leukemias.
CBC catches it even though the pt is feeling great.
Most pts with chronic leukemias are asymptomatic at time of dx.
7
Q
What 3 diagnostic symptoms are you most likely to see in AML?
A
- Renal failure
- Hyperuricemia
- Azotemia
8
Q
2 chemicals labeled as causative factors of AML:
A
Benzene
Toluene
9
Q
Which 2 subtypes of AML are more likely to have CNS involvement?
A
M4 and M5
10
Q
Which 2 subtypes of AML are more likely to involve the skin (Sweet’s syndrome)?
A
M4 and M5
11
Q
TQ
Gingival hypertrophy from infiltration by myeloblasts occurs in:
A
M4 and M5
12
Q
What is the MC cytogenetic translocation seen in M2?
A
t (8 ; 21)
13
Q
t (15 : 17) is pathognomonic for what AML subtype?
A
M3
acute promyelocytic leukemia; APL
14
Q
TQ
- MC malignancy in childhood
- Whites, males
- Assoc with HTLV-1 ***
A
Acute lymphocytic leukemia (ALL)
15
Q
TQ
T-cell leukemias have a higher incidence of mass in what specific location?
A
Mediastinal masses (thorax)
Rule of T’s:
- T-cell leukemias
- Located on Thorax (mediastinum)
- HTLV-1
16
Q
Leukostasis occurs more frequently in:
A
AML
17
Q
Lymph node and splenic enlargement are more common in:
A
ALL
18
Q
How does age factor into prognosis of ALL?
A
Young age assoc with better prognosis (e.g., children 2 to 10 years of age do best)
19
Q
TQ
In the treatment of AML, what is given in the induction phase?
A
3 + 7 (Anthracycline (Donarubicin or Inarubicin) and Ara-C)
20
Q
TQ
In the treatment of AML, what is given in the consolidation phase?
A
High dose Ara-C (HDAC)
21
Q
TQ
In the treatment of AML, what is given in the maintenance phase?
A
ATRA
-for APL (M3) ONLY!
22
Q
TQ
In the treatment of ALL, what is given in the induction phase?
A
Vincristine/Prednisone + others
23
Q
TQ
In the treatment of ALL, what is given in the consolidation phase?
A
Multiple agents + CNS prophylaxis (MTX or Ara-C)
24
Q
TQ
In the treatment of ALL, what is given in the maintenance phase?
A
6-MP and MTX
25
TQ
- An acquired clonal disorder involving the hematopoietic stem cell characterized by a prominent expansion of the granulocyte compartment
- Cause: increases with radiation ***
- MC in 5th and 6th decade, although childhood cases have been reported
Chronic myelocytic leukemia (CML)
26
TQ
| The chronic phase of CML is characterized by:
Leukocytosis and indolent disease course
- Chronic phase is 5-7 years
- Most cells in blood are mature granulocytes
27
TQ
| The accelerated phase of CML is characterized by:
- Increased leukocytosis
- Immature granulocytes appear in peripheral blood
- Platelet and RBC counts begin to drop
28
TQ
The blast phase of CML is morphologically similar to AML, except that it is:
What are 2 prominent features of CML?
10% of pts who develop blast crisis will also have what?
Resistant to treatment
- Anemia and thrombocytopenia prominent
- 10% of pts who develop blast crisis will also have a lymphoid crisis (will also develop ALL due to it being a stem cell abnormality)
29
TQ
| What is the MC cytogenetic translocation seen in CML?
Ph; t (9 ; 22) (q34 ; q11)
30
TQ
| A decreased leukocyte alkaline phosphatase (LAP) score is diagnostic of:
CML
31
TQ
| The initial treatment of choice of CML is:
TKIs
| BCR/abl tyrosine kinase inhibitors
32
```
TQ
What are the goals and benchmarks for treatment of CML with a TKI?
3-6 mo:
6 mo:
12 mo:
18 mo:
```
3-6 mo: complete hematologic response
6 mo: any cytogenetic response
12 mo: major cytogenetic response (50-75% reduction)
18 mo: complete cytogenetic response (cannot see anything resembling CML whatsoever)
33
TQ
- MC chronic leukemia
- Affects those ages 60+
- Males more common
- B-cell origin more common
Chronic lymphocytic leukemia (CLL)
34
What are a few associated abnormalities with CLL?
| Think anemia-related...
- 10-20% of pts have Coombs positive hemolytic anemia
- Abs usually warm-reacting IgG
- 95% of cases have immunoglobulin coating the surface of CLL cells (usually IgM if on CLL cells)
- Hypogammaglobulinemia (due to intrinsic defect in B lymphocyte)
35
TQ
CLL can develop into what other neoplasm?
What syndrome is this called?
CLL >> Large cell lymphoma
Richter's syndrome
36
TQ
| "Smudge cells" are seen in the peripheral smear of:
CLL
37
Dx:
What is the link between B cell and T cell neoplasms in terms of surface antigens? (i.e., why can CLL turn into large cell lymphoma?)
CD5
B cell markers = CD19, CD20, CD23
-Co-expression of CD5 in CLL (aberrantly expressed)
38
TQ
Which translocation is assoc with a worse prognosis in CLL?
What is the most frequent abnormality encountered?
t (11 ; 14) – translocates a gene called bcl-1 next to a gene regulating immunoglobulin production, assoc with worse prognosis
Most frequent abnormality encountered in CLL = Trisomy 12
39
TQ
| Describe the Rai staging system for CLL (stages 0–IV).
Stage 0: Lymphocytosis only (ALC > 10,000/mm3) – 150 mo survival
Stage I: + LAD – 101 mo survival
Stage II: + hepatosplenomegaly – 71 mo survival
Stage III: + anemia (Hb < 11 gm) – 22 mo survival
Stage IV: + thrombocytopenia (< 100,000) – 11 mo survival
40
Increased fungal sepsis is seen in which chemotherapeutic drug used for B-CLL?
Fludarabine
41
TQ
| What virus reactivation should you be aware of with ANY anti-CD20 monoclonal Ab (ofatumumab, obinituzumab)?
Hepatitis B
42
Treatment is not needed for CLL pts in which Rai stages?
Tx not needed for stages 0, I or II
43
What is the 3-drug treatment regimen for younger pts with CLL?
Fludarabine / Cytoxan / Rituxan
44
What are the 2 treatment regimen options for older pts with CLL?
Chlorambucil +/– Prednisone
or
Bendamustine / Rituxan
45
For the severely ill pt with CLL, what is the treatment?
NO treatment.
46
What are the two major categories of HL?
- Classical
| - Nodular lymphocyte predominant HL
47
```
TQ!
Which form of classical HL has the worst prognosis?
A. Lymphocyte predominant
B. Nodular Sclerosis
C. Mixed Cellularity
D. Lymphocyte depleted
```
D. Lymphocyte Depleted
48
What are the two patterns of spread for HL?
-Usually starts as focal microscopic disease in a peripheral lymph node (usually cervical)
-Contiguity model: local process and spreads to contiguous lymph nodes, hematogenous spread occurs late
-Susceptibility model: systemic disease from infection by an oncogenic virus

49
Pt with constitutional HL presents with...
- Fatigue, weakness, anorexia, cachexia, pruritis
- Lymph node pain after EtOH ingestion
- Impaired immunity
- B symptoms
TQ
What are B symptoms? Why are they impt?
- Weight loss > 10% of body wt. in 6 months prior to dx
- Drenching night sweats
- Unexplained fever with temp. > 38oC
Associated with 20-30% reduction in survival
50
What kind of biopsy do we need in HL?
excisional NOT FNA of LN
51
How do we stage HL using the Ann Arbor Staging System? (Hint 4 stages)
I: Single LN
II. 2+ LN on same side of diaphragm
III. LN on both sides of diaphragm
IV: Many LN or BM involvement
All cases sub-classified into absence (A) or presence (B) of B symptoms
52
TQ
| What tx do we use for pts with stage I or II HL?
Radiation therapy ! curative!
| w/ chemo in 3-4 cycles for high risk or bulky dz
53
TQ
| When do we use chemo in HL? What does it consist of?
- Stage III or IV
- ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)
(w/ radiation for residual dz)
54
SE of chemo using ABVD for HL?
- cardiotoxicity
- pulmonary toxicity (bleomycin)
- Neutropenia, thrombocytopenia
55
TQ
| How do we treat large mediastinal masses in HL?
chemotherapy followed by radiation
| cant do initial radiation because too large a field-->risky
56
TQ
| How do we treat relapses in HL?
- modality other than that used for primary tx
| - BM transplant?
57
What are the three general categories of lymphoma based on untreated survival?
- Indolent: survival measured in years
- Aggressive: survival measured in months
- Highly Aggressive: survival measured in weeks
58
TQ!
Pt on graft-rejection medications for transplant. Presents with acute altered mental status, seizures, confusion
MRI shows big lesion in brain
Primary CNS lymphoma as result of chronic immunosuppression
59
Higher incidence of lymphoma in what 3 pt groups?
- AIDS
- transplant recipients
- genetic immunodeficiency patients (Wiskott-Aldrich syndrome, X linked agammaglobulinemia, etc.)
60
TQ
- often asymptomatic, disease discovered incidentally on evaluation for something else
- B symptoms may be present
- Infrequently present with peripheral adenopathy, but may have massive mediastinal or retroperitoneal node involvement
Indolent lymphoma
61
TQ
-history of waxing and waning adenopathy for several weeks or months
-Constitutional symptoms (fatigue, weakness, weight loss) more often
Splenomegaly
Aggressive lymphoma
62
TQ
- rapid development of adenopathy and symptoms
- Frequently present with an isolated lesion that "came up overnight”
Highly aggressive lymphoma
63
TQ
Indolent lymphomas often present as which stage?
What about aggressive and highly aggressive?
- Indolent lymphomas often present with advanced (Stage III or IV) disease
- Aggressive and highly aggressive lymphomas frequently present with lower stage (Stage I or II) disease
64
TQ
| What is richter's syndrome?
large cell lymphoma arising from chronic lymphocytic leukemia (CLL)
65
TQ
| What is the classification system for NHL? What about staging?
R.E.A.L classification
| Ann arbor staging like HL
66
What is more often elevated in NHL, especially indolent lymphomas?
Beta-2 microglobulin
67
What is mandatory for diagnosis of lymphoma?
LN biopsy!
68
- What is the potentially curative modality used for disease confined to one or two nodal sites on one side of the diaphragm (Stages I and II)
- Also of value for local compressive symptoms (cord compression, SVC syndrome, tracheal compression from mediastinal mass), and for consolidative treatment of masses treated by chemotherapy
Radiotherapy
| If high risk (large or 3+ on one side of diaphragm) then give chemo first
69
How do we treat stage III and IV NHL? What is the combination?
- Chemo
| - RCHOP (Rituximab (CD20), Cyclophosphamide, doxorubicin, vincristine, prednisone)
70
What is the treatment of aggressive lymphoma?
- combination chemo at ALL STAGES
| - radiation to shrink large masses
71
What is the treatment of highly aggressive lymphoma?
-Treat like acute lymphocytic leukemia
72
Prognosis:
- Indolent: median duration of survival is _ years (most incurable)
- Aggressive: median duration of survival is _ years, but the 50% of patients who make it past 5 years are cured
- Patients who are treated at a lower stage have better prognoses than those patients with the same histology who are treated at a higher stage
8
4
73
- Disorders of the pluripotential stem cell
- Characterized by ineffective hematopoiesis (Proliferative defects, differentiation abnormalities, impaired apoptosis)
- Pancytopenia with hyperplastic marrow
- Usually occurs 60-70 yo
Myelodysplastic syndromes
74
Causes of myelodysplastic syndromes?
- Chemo for other cancers (breast, HL, NHL: alkylating agents and anthracyclines)
- Radiation (atomic bomb survivors, Chernobyl, therapeutic)
- Petrochemical exposure (farmers)
75
TQ!
| What are the cytogenetic abnormalities assoc with myelodysplastic syndromes?
- Partial or total loss of long arm of chromosome 5 or 7
- Inversion of chromosome 16
- Trisomy 8
76
Pt presents with...
- Constitutional symptoms: Fatigue, pallor, bleeding, infection
- Pancytopenia
- Incr LDH
- Incr serum ferritin
- serum Fe and TIBC normal
Myelodysplastic syndrome
| half are asymptomatic
77
- Erythropoiesis varies from hypoplasia to hyperplasia, often massively ineffective
- Other cell lines involved (WBCs, platelets) and may have cytopenias in peripheral blood with decreased or increased activity in marrow
- Often megaloblastic (distinguish from B12/folate)
- Often asymptomatic but some require transfusion or supp EPO
Refractory Anemia (RA)
Subsets: Refractory cytopenia with uni or multi lineage dysplasia
78
- Ringed sideroblasts in marrow precursors
- Mitochondria laden with Fe encircling the nucleus of the erythroid precursors
- Lowest risk of conversion to AML (10-15%)
Refractory Anemia with Ringed Sideroblasts (RARS)
79
TQ
| What must we check in RARS pts to be sure of our diagnosis?
Check B6 level on every patient with ringed sideroblasts!
- Pyridoxine Deficiency (Vit B6 def) also causes ringed sideroblasts
- Replace B6 for at least 6 months if deficient, if no improvement=pyridoxine resistant sideroblastic anemia (RARS)
80
- Refractory anemia with 5-20% myeloblasts in bone marrow
- High rate of conversion to AML (50%)
- Often profound pancytopenia
- Most pts transfusion dependent
- Cytogenetic abnormalities more pronounced that RA or RARS
Refractory Anemia with Excess Blasts (RAEB)
81
TQ
- Refractory anemia with 20-30% myeloblasts in bone marrow
- Cytogenetics even more abnormal
- ***Highest rate of conversion to AML (65-75%)
- Circulating myeloblasts in peripheral blood in 25-40% of cases
- Often managed like de novo AML but much more refractory to AML-style treatment
Refractory Anemia with Excess Blasts in Transformation (RAEB-T)
(to AML...)
82
- Trilineage dysplastic changes in hematopoietic precursors separate this as dysplasic rather than proliferative
- Marrow myeloblasts 5-30%
- Absolute monocyte count > 1000/cc OR > 10% monocytoid cells in marrow
- Very chronic clinical course with ~25% conversion rate to AML
- NO Philadelphia chromosome!
CMML
| NOT a variant of CML
83
```
Myelodysplasias clinical course:
-poor prognosis: __ yr survival
Adverse prognosis:
-Marrow blasts > 5%
-Platelets 60 years
```
2
84
Cytogenetic abnormalities-->prognosis in myelodysplasias?
- Monosomy 7
- Hypodiploidy
- Multiple abnormalities
85
TQ!!
| Favorable prognosis in myelodysplasias? (cytogenetic)
5q- syndrome: beneficial responses to lenalidomide reported
86
TQ
| How do we score myelodysplasia?
IPSS score! 4 risk groups..
Low: IPSS 0, survival 5.7 yrs
Intermed 1: IPSS 0.5-1.0, survival 3.5 yrs
Intermed 2: IPSS 1.5-2.0, survival 1.2 yrs
High: IPSS 2.5-3.5, survival 0.4 yrs (4 months)
87
Supportive Care for myelodysplasia:
-Avoid medications that damage marrow
-Aggressive treatment of infections
-Transfuse PRBCs when symptomatic
-Transfuse platelets only for bleeding or in preparation for surgery
-Watch for iron overload-desferrioxamine (Desferal) if present
-Supplemental vitamins not needed if chemical assays normal
(B6 may be exception)
-Androgens effective if hypoplastic marrow (lots of SE)
-NO Corticosteroids (toxicity)
What is the importance of keeping EPO below 500?
Erythropoietin may decrease or ameliorate transfusion requirement in some pts! However, serum EPO level > 500 predicts for poor response
88
TQ!
Pt <60 yo in good status with IPSS intermed 2 or high risk myelodysplasia categories are considered for what type of therapy?
What if they were IPSS low or intermed-1 category?
High intensity therapies
Low intensity therapy/supportive care
89
TQ
Pt >60 yo in good status with IPSS intermed 2 or high risk myelodysplasia categories are considered for what type of therapy?
What if they were IPSS low or intermed-1 category?
Low intensity therapies b/c of age! (selective for high intensity depending on health)
Low intensity therapy/supportive care
90
TQ
| T/F: Myelodysplasia pts with poor performance status receive palliative care regardless of age
TRUE
91
TQ
Low/intermediate intensity therapy for myelodysplasia consists of what two drugs?
Which third drug is used ONLY in 5q- syndrome?
Hypo/demethylating agents:
1. Azacitidine (Vidaza®)
2. Decitabine (Dacogen®)
3. Lenalidomide (Revlimid®)
92
High intensity therapy for myelodysplasia includes what type of therapy?
- AML induction-style treatment
- Not as effective as de novo AML
(-Response rate=54% with 15% mortality rate at 30 days
-Medial survival 13-15 months)
93
When should hematopoietic stem cell transplantation be considered in myelodysplasia?
-Pts <60 w/ HLA-matched sibling donor
(Significant chance of cure after allo-HCT in low and intermediate risk patients, high transplant-related mortality and relapse)
94
All of the following are examples of what type of syndromes?
- Polycythemia Vera (P.V.)
- Essential Thrombocythemia -Chronic Myelocytic Leukemia (CML)
- Myelofibrosis (Agnogenic Myeloid Metaplasia, AMM)
- Sometimes Chronic Lymphocytic Leukemia (CLL)
Myeloproliferative Syndromes
95
- Increased #s in the peripheral blood of any of the circulating cellular elements,
- Result from primary proliferation of stem cells in the marrow
- Chromosomal aberrations include JAK-2 and MPL (thrombopoietin receptor)
Myeloproliferative Syndromes
96
- Panhyperplasia of marrow (panmyelosis)
- Involves all cell lines (esp erythroid precursors)
- A clonal stem cell disorder
- Male:Female Ratio = 1.4:1
- Higher incidence in Jews of European extraction
- Rarely familial
- 80% of all cases occur in patients over age 50
- Chronic malignancy
Polycythemia Vera
97
```
TQ!!
Pt presents with...Dx?
-**Facial rubor (red face)
-**Pruritis with hot shower or bath
-Hyperviscosity signs such as headache, dizziness, blurred vision, heaviness in arms or legs
-Splenomegaly
```
Polycythemia Vera
98
What lab findings will you see in PV?
-Incr RBC numbers (Hb/Hct)
-Incr LAP
-Incr WBC and/or platelet counts
(20-50,000/μl WBC & 650,000-1,000,000/μl platelets)
99
TQ
| How does PV BM histo differ from myelodysplasia?
Hypercellular but NO dyserythropoiesis!
Also see incr reticulin later on (spent phase)
100
TQ!!
- Without treatment, 50% mortality at 18 months
- With treatment patients can live for years to decades
- Usual cause of death in treated patients is progressive marrow fibrosis with pancytopenia a.k.a. "spent phase" polycythemia
What is the MOST important risk assoc with PV?????
Since incr risk of thrombotic and hemorrhagic complications PV has been linked to Budd-Chiari Syndrome!!!!
101
Why are the following all impt when diagnosing a pt with PV?
- Hemoconcentration (dehydrated)
- Pulmonary disease-COPD (smokers polycythemia)
- EPO producing tumors (renal cell carcinoma, neuroendocrine tumors)
- Hemoglobinopathy with high affinity hemoglobin
- Living at high altitude
These are all differentials and secondary causes of elevated RBCs...must exclude each one by one when working up for PV!
(Eval lung with pulse oximetry and PFT w/ DLCO)
102
What mutation is present in over 95% of patients with myeloproliferative disorders including PV?
Janus Kinase (JAK) Mutations (JAK2/V617F)
103
How do we tx PV?
| Goal=lowering of RBC mass essential to avoid hyperviscosity complications
Phlebotomy!
250-500 cc whole blood every 1-2 weeks as long as Hct > 50%
Avoid alkylating agents (cause leukemia)
104
A primary myeloproliferative disorder characterized by marrow fibrosis and extramedullary hematopoiesis
Myelofibrosis
105
What is the Myelofibrosis triad?
Leukoerythroblastic anemia
Poikilocytosis
Splenomegaly
106
- Increased reticulin deposition in marrow
- Secondary to incr platelet derived growth factor (PDGF) and other cytokines in marrow
- Increased marrow megakaryocytes can be seen
- Chronic stimulus to marrow fibroblasts that then make reticulin
- Marrow architecture disrupted with subsequent mobilization of marrow stem cells to extramedullary sites (spleen, liver, lungs)
Myelofibrosis
107
T/F
| JAK2 mutations are always seen in myelofibrosis ?
FALSE!
Can assist in diagnosis, but a large percentage of true primary myelofibrosis patients can be JAK negative
108
Myelofibrosis:
-Chronic, asymptomatic, and progressive with pancytopenia and organomegaly later
How do we treat?
- Observe! No therapy available for reversal of fibrosis
- Manage pancytopenia with transfusion or EPO
- Hydroxyurea helps with splenomegaly
ONLY cure is stem cell transplant
109
What is the new JAK inhibitor approved for treatment of intermediate and high risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis?
Ruxolitinib (Jakafi®)
110
Primary marrow disorder characterized by increased platelet numbers in peripheral blood and increased megakaryocytes in marrow
What is this disorder called and what is the main assoc. problems?
Essential thrombocythemia
- Resultant problems are thrombosis and bleeding
- Note: increased risk of development of leukemia
111
What is the criteria for dx of ET?
- **Sustained platelet count ≥450,000/cc
- Bone marrow biopsy: prolif of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes
- no significant increase or left-shift of neutrophil granulopoiesis or erythropoiesis
- Not meeting WHO criteria for PV, MF, CML, MDS or other myeloid neoplasm
- Demonstration of JAK2 or other clonal marker, or in the absence of a clonal marker, no evidence for reactive thrombocytosis
112
TQ
| What are the 2 main thrombotic complications of ET?
- Digital ischemia
- Erythromelalgia
(others include:TIA/Stroke, amaurosis fugax, MI, migraine, syncope, Budd-Chiari syndrome)
113
TQ
- Burning pain accompanied by redness and increased skin temperature
- Exacerbation of symptoms with increasing temperatures or cooling the skin
- Biopsy demonstrates arteriolar inflammation and thrombotic occlusions
- ASA improves symptoms
Erythromelalgia assoc with ET
114
Pt presents with complaints of incr bruising, epistaxis, superficial mucosal hemorrhages, and bleeding post surgery
Clinical exam otherwise normal
Consider ET
115
Lab findings for ET?
- Incr platelet count (even > 1,000,000/μl)
- Normal or incr WBC count
- Normal or decr Hb/Hct
- Marrow exam...normocellular to hypercellular w/ incr megakaryocytes and minimal reticulin
- Abnormal platelet fx despite normal bleeding time
116
TQ
| What disease is ET assoc with?
von Willebrand's disease (vWD)
(This is an acquired form of vWD, NOT a familial disorder!)
- Reduction in large multimer forms of vWF protein
- Resembles Type II vWD
117
TQ
| Tx of ET if asymptomatic?
NONE! Dont tx!!
If symptomatic, hydroxyurea, busulfan, chlorambucil, melphalan all appear to be effective with plateletpheresis or alfa IFN
118
A new agent with antiproliferative properties, helpful in treating ET if refractory to other meds
Anagrelide (Agrylin®)
119
Are JAK inhibitors approved for ET tx?
NO!
| JAK inhibitors have NOT been approved for treatment of ET!
120
All of the following are examples of what type of disease?
- Monoclonal Gammopathy of Unknown Significance (MGUS)
- Solitary Plasmacytoma of Bone
- Indolent myeloma
- Multiple myeloma
- Waldenström's macroglobulinemia
- Heavy Chain Diseases
Specific Plasma Cell Dyscrasias
121
Plasma cell dyscrasia:
- A condition in which there is clonal proliferation and immortalization of immunoglobulin-secreting plasma cells
- Immunoglobulin gene rearrangements lead to expression of a unique idiotype
What is the hallmark feature?
- Isolated peak in the gamma region on serum protein electrophoresis=immunoglobulin molecule (the myeloma protein, or M-protein)
- In some diseases, only light chains or heavy chains may be produced
122
- Presence of M-protein in serum or urine without identifiable disease
- M-protein < 3 gm/dl for IgG or < 2.5 gm/dl for IgA
- Urine light chains < 5%
Monoclonal Gammopathy of Unknown Significance
123
Which Ig do most MGUS pts secrete
IgG!
124
MGUS is in 1% of pts >50 and in 3% of pts >70 and is usually asymptomatic
So why do we worry about it?
- Immune hemolysis, peripheral neuropathy, renal disease may occur
- 20% develop B cell neoplasia, myeloma, macroglobulinemia, or lymphoma
125
How do we tx MGUS?
- Supportive care only (unless malignancy is present)
| - May need to treat associated problems (plasmapheresis?)
126
- Single area of bone destruction
- Negative bone survey and MRI of thoracolumbar spine
- Normal bone marrow
- No or low level M-protein with normal levels of immunoglobulins
- Local radiotherapy alone (4000 cGy) curative in ~30%
- Long survival time, median 10 years
Solitary Plasmacytoma of Bone
127
-Asymptomatic with coincidental diagnosis of low tumor mass
-Follow on no treatment
-Early progression in some (those with bone lesions, local tumors on MRI of spine, Bence Jones proteins)
-Late progression in most
-All patients retain sensitivity to chemotherapy, thus don't treat until symptoms of myeloma present
-Long survival time, median 8 years

Indolent Myeloma
128
- A disseminated malignancy resulting from a clonal proliferation of transformed plasma cells in bone marrow
- Malignant cells secrete M-protein in direct proportion to tumor burden
- 60 yo, males, blacks
Multiple Myeloma
129
Pathophys of Multiple Myeloma?
Single plasma cell undergoes malignant transformation-->
Grows-->
Disseminates to distant sites in BM-->
Diffuse nodules w/ sheets of plasma cells within the marrow-->
Release osteoclast activators
130
What kind of anemia does multiple myeloma cause?
Normochromic normocytic anemia
- Inhibition of erythropoiesis
- Disturbance of marrow architecture
- Immune mediated hemolysis
131
TQ
| What are the main clinical manifestations of multiple myeloma?
- Lytic bone lesions (fracture + bone pain)
| - Hypercalcemia with hypercalciuria (STONES)
132
TQ!
| Mild hypercalcemia + kidney stones=????
workup for multiple myeloma!!!
133
T/F: Multiple myeloma pts have no incr risk of serious systemic infx
FALSE!
Over 75% of myeloma patients have a serious systemic infection at some point in disease course due to the following:
-Hypogammaglobulinemia—decr Ig -Increased T-suppressor levels
-Poor antibody response to polysaccharide antigens (bacterial cell walls), despite normal T-cell function
134
TQ
| What are the two most frequent infections of multiple myeloma and their pathogens?
-pneumonias and pyelonephritis
- Most frequent pathogens are S. pneumoniae, S. aureus, and K. pneumoniae in the lung &
- E. coli and other gram negative enterics in the urinary tract
135
What do we see in urine of a multiple myeloma pt? Explain
Bence jones proteins
-Light chains are rapidly removed and metabolized by the kidney and appear in urine when renal threshold is excreted (Bence Jones proteins)
(Light chains may also be deposited in tissues (amyloidosis))
136
- May cause hyperviscosity in a multiple myeloma pt
- May bind with coagulation factors causing coagulopathy
- May form cryoglobulin leading to Raynaud's phenomenon and potential gangrene after exposure to cold
M-protein of multiple myeloma
137
What is the most common cause of renal failure in multiple myeloma pts?
- "Blocked pipe" appearance is hallmark
- Myeloma kidney—eosinophilic casts surrounded by epithelial syncytium in distal tubules and collecting ducts
- Acquired Fanconi's syndrome may be seen
calcium nephropathy
138
TQ!
| Along with Rouleaux formation, what is another key feature of multiple myeloma labs?
High erythrocyte sedimentation rate (ESR)! (incr protein)
139
What is the classic triad for multiple myeloma?
- Marrow plasmacytosis (> 10%)
- Lytic bone lesions
- Serum and/or urine M-protein
(Diagnosis may be made in absence of bone lesions if plasmacytosis is assoc w/ increase in M-protein over time or if extramedullary mass lesions develop (chloroma))
140
Tests ordered for multiple myeloma:
- CBC
- Renal function tests
- Serum calcium and albumin
- Serum protein electrophoresis (SPEP) OR
- 24 hour urine protein electrophoresis (UPEP)
- Bone marrow aspirate
TQ!
How do we image the bones???
Skeletal x-ray survey
NOT bone scan!!! not helpful as osteoblast inhibition by OAF's inhibit uptake of radionuclide

141
TQ
| How can we distinguish MGUS from myeloma on electrophoresis?
albumin peak smaller than gamma in myeloma and gamma is very high!
In MGUS, the albumin peak is high and the gamma is lower
142
TQ!!
| Impt to distinguish situations needing chemo...DO NOT TREAT which pts?!
- Indolent myeloma—can be observed off therapy until symptoms arise
- MGUS—it's not a malignancy
- Solitary plasmacytoma of bone—radiotherapy!
- Concomitant medical illness making chemotherapy risky (sepsis). Can proceed when stable
143
What is the standard frontline tx for myeloma?
Oral angiogenesis inhibitor:
- Thalidomide (Thalomid®) or
- Lenalidomide (Revlimid®)..risk in pregnancy
144
Myeloma pt presents with...suspect what?
- Suspect in patients presenting with lethargy, polyuria, constipation, nausea/ vomiting, mental confusion, or developing coma
- Degree of symptoms usually correlates better with serum ionized Ca than total Ca
- Immobilized patients tend to develop hypercalcemia easier than active patients
hypercalcemia
145
Tx of hypercalcemia assoc with myeloma?
- Modest increases in serum Ca (11.5-12.0 mg/dl) usually respond to hydration
- High Ca levels (>16 mg/dl) =emergency: Manage with IV hydration + bisphosphonates (zolendronic acid or pamidronate)
(Parenteral calcitonin may be used if Ca level is very high (>18 mg/dl)...only lasts a few hours)
146
Myeloma pt developing neurologic symptoms in lower extremities plus focal back pain...
Dx?
Standard imaging of choice=MRI
Extradural cord compression until proven otherwise!
Spinal cord compression assoc. with myeloma:
147
Tx of spinal cord compression assoc. with myeloma?
- High dose steroids (Dexamethasone 10-30 mg IV bolus, followed by 4-8 mg every 4-6 hours)
- Emergency radiotherapy (delay in tx=paralyzed)
148
TQ
Tx of lytic bone dz assoc with myeloma? (2)
Must decr risk of fracture!
```
Pamidronate (Aredia®)
Zolendronic acid (Zometa®)
```
149
- Plasma cell malignancy in which affected cells secrete IgM (high M-protein >3 g/dl)
- In contrast to myeloma, lymphadenopathy and hepatosplenomegaly
- **Major feature is hyperviscosity syndrome (-->retinal change)
- More common in men and >40 yo
- Minimal excretion in the urine
Waldenström's Macroglobulinemia
150
- Weakness, fatigue, recurrent infections
- Epistaxis, visual disturbances, neurologic symptoms (peripheral neuropathy, dizziness, headache, transient paresis)
- Hepatosplenomegaly, adenopathy
- **Segmental dilatation of retinal veins (sausage links) on opthalmoscopic exam—characteristic of hyperviscosity states
Waldenström's Macroglobulinemia
151
What kind of anemia is Waldenström's Macroglobulinemia?
Normochromic normocytic anemia:
- Rouleaux formation and + Coombs test
- Malignant cells in peripheral blood
- Cryoglobulinemia—Raynaud's phenomenon and cryopathic changes may occur
152
Tx of Waldenström's Macroglobulinemia?
Plasmapheresis can decrease M-protein levels quickly since
Identical tx to that of myeloma
Median survival is > 3 years
153
TQ!!!
-Rare lymphoplasmacytic malignancies in which a defective heavy chain is secreted
- Heavy chain usually has intact Fc fragment
- Gamma, alpha, delta, and mu diseases have been reported
Heavy Chain Disease
154
TQ
-a.k.a. Franklin's Disease
-lymphadenopathy, fever, anemia, malaise, hepatosplenomegaly, and weakness
-Palatal edema—nodal involvement of Waldeyer's ring-->obstructive respiratory symptoms
-Disease course—rapid deterioration and death from infection

Gamma Heavy Chain Disease
155
TQ
| Dx of Gamma Heavy Chain Disease?
Serum M-protein that reacts with anti-IgG reagents but not anti-light chain reagents
156
TQ
- a.k.a. Seligmann's Disease
- Most common heavy chain disease
- Related to Mediterranean lymphoma (immunoproliferative small intestinal disease —IPSID)
- Known relationship to intestinal parasites
- Infiltration of lamina propria of intestine with lymphoplasmacytic cells that secrete truncated alpha chains
Alpha Heavy Chain Disease
157
TQ
- Chronic diarrhea
- Weight loss
- Malabsorption
- Mesenteric and paraaortic adenopathy
- Respiratory and upper aerodigestive involvement rarely
Which heavy chain dz and treatment?
Alpha Heavy Chain Disease
- Chemotherapy may produce long-term remissions
- Some patients respond to antibiotics—possible chronic antigenic stimulation by intestinal pathogen is consideration as etiology
158
-Occurs in very rare subset of patients with chronic lymphocytic leukemia
-May see vacuoles in malignant lymphocytes and excretion of kappa light chains in urine
-Tumor cells seem to have defect in secretion of BOTH light and heavy chains
-Treatment is per typical chronic lymphocytic leukemia

Mu Heavy Chain Disease
159
- Systemic illness resulting from deposition of polymerized immunoglobulin light chain fragments in organs and tissues
- Ig molecules are arranged in beta-pleated sheet configuration
- Appear as homogeneous pink-staining material on light microscopy of H & E stained tissue sections
Primary Amyloidosis
160
Clinical features of _____ ________:
- Musculoskeletal—decreased joint range of motion, carpal tunnel syndrome
- Neurologic—peripheral neuropathy, postural hypotension
- Hematologic—easy bruising and bleeding (endothelial damage)
primary amyloidosis
161
- Edema
- Weakness, light headedness
- Paresthesias
- Shortness of breath
- "Shoulder pad sign"—from shoulder muscle infiltration
- "Raccoon sign"—from periorbital hemorrhage
Primary amyloidosis
162
Leading cause of death of primary amyloidosis?
-Renal failure and heart failure leading causes of death
- Median survival one year
- Treating underlying disorder early in its course may be helpful, but of little benefit for advanced cases
- Amyloid rarely regresses once deposited
163
- Arises from epidermal keratinocytes
- Usually seen in fair-skinned persons with excessive sun exposure
- MC in men (3:1)
- Typical risk factors, including HPV infection
Squamous cell carcinoma
164
- Sun-exposed areas
- Red, hardened papule
- Actinic keratosis
- Occurs in older pts
Clinical presentation of:
Squamous cell carcinoma
165
Precursor lesions of squamous cell carcinoma:
- Bowen's dz (carcinoma in situ)
- Cutaneous horn
- Chronic ulcers
- Scar tissues
- Radiodermatitis
166
How is SCC diagnosed?
Biopsy – punch, shave, excision
167
Treatments for SCC:
- Cryosurgery
- Surgical excision
- Topical chemotherapy (5-FU)
- Systemic chemotherapy (5-FU, Cisplatin) if metastatic dz for palliation
168
- Arises from immature pluripotent cells of the epidermis
- Accounts for 70% of all non-melanoma skin cancers
- Sun-exposed areas
- Assoc with basal cell nevus syndrome, Bazex's syndrome, and the genodermatoses
Basal cell carcinoma
169
- Tends to occur in older pts
- Slowly growing, shiny, pink papule with telangiectasias
- Over time, ulcerates and forms rolled borders
Basal cell carcinoma
170
Treatments for basal cell carcinoma:
- Surgical excision
- Mohs surgery
- Electrodissection
- Cryosurgery
- Laser treatment
171
Treatments of recurrence of basal cell carcinoma:
- Repeat resection
- Radiation therapy
- Topical chemotherapy
172
What are the unique arm presentations for melanoma between men and women?
Man's LEFT arm
| Woman's RIGHT arm
173
Risk factors for melanoma:
- As per non-melanoma skin cancers
- Dysplastic nevus syndrome
- Actinic keratoses (topical liquid N2 or 5-FU)
174
- MC histological variety of melanoma (70%)
- Generally arises in preexisting nevus
- Often slowly changes over months to years
- Characteristic notching or indentation of the perimeter of the lesion
Superficial spreading melanoma (SSM)
175
- 2nd MC histological variety of melanoma (15-30%)
- More aggressive
- Blue-black in color with faster growth rate than SSM
- Often raised or dome-shaped
- Lack horizontal growth phase, thus have sharply demarcated borders
Nodular melanoma
176
- Uncommon histological variety of melanoma (4-10%)
- Low potential for metastasis
- Typically occur on face of older white women (uncommon before age 50)
- Usually large (> 3cm)
- Sun related changes in dermis and epidermis needed for diagnosis
- Borders often convoluted with prominent notching and indentation
Lentigo maligna (Hutchinson's freckle)
177
- Characteristically appear on palms of hands and soles of feet or on nail beds (subungual melanoma)
- MC in non-whites
- Occur in older pts (> 60)
- May see a "haphazard" array of color
Acral lentiginous melanoma
178
Describe melanoma staging in terms of Breslow thickness.
Thin melanomas:
Thick melanomas:
```
Breslow thickness – measured using ocular staging micrometer.
Thin melanoma (< 0.75mm) have approx 85% DFS at 10 years post-diagnosis.
Thick melanoma (> 4.0mm) have < 20% DFS at 5 years post-diagnosis.
```
179
Flat lesion with well-circumscribed change in skin color < 1 cm:
e.g., Freckle
Macule
180
Macule > 1 cm:
| e.g., Large birthmark (congenital nevus)
Patch
181
Elevated solid skin lesion < 1 cm:
| e.g., Mole (nevus), acne
Papule
182
Nonpustular, non-vesicular lesion on skin > 1 cm:
Nodule
183
Small fluid-containing blister < 1 cm:
| e.g., Chicken pox (varicella), shingles (zoster)
Vesicle
184
Large fluid-containing blister > 1 cm:
| e.g., Bullous pemphigoid
Bulla
185
Vesicle containing pus:
i. e., collection of leukocytes in the epidermis
e. g., Pustular psoriasis
Pustule
186
Papule > 1 cm:
| e.g., Psoriasis
Plaque
187
- Erythematous lesion
- Non-scaling
- Localized with sepsis
What condition meets this description?
Cellulitis
188
- Erythematous lesion
- Non-scaling
- Localized without sepsis
What 3 conditions meet this description?
Insect bites
Acne
Hemangioma
189
- Erythematous lesion
- Non-scaling
- Generalized +/– systemic signs
What 4 conditions meet this description?
Urticaria
Erythema nodosum
Viral exanthems
Annular erythemas
190
- Erythematous lesion
- Scaling
- Papulosquamous
What 4 conditions meet this description?
Pityriasis
Psoriasis
Tinea corporis
Syphilis
others...
191
- Erythematous lesion
- Scaling
- Eczematous
What 3 conditions meet this description?
Atopic dermatitis
Contact dermatitis
Scabies
others...
192
- Xerosis (dry skin) and ichthyosis vulgaris (dry, scaly skin)
- Erythematous (pigmentary changes)
- Eye and periorbital changes
- Hand and foot dermatitis
- T-cell pathogenesis
Atopic dermatitis
193
- Acute, painful, spreading infection of dermis and subcutaneous tissues
- Tender, warm, poorly demarcated, boggy plaque
- MC on extremity
- Often due to trauma or another infection
- Usually S. pyogenes or S. aureus
Cellulitis
194
- Symmetric, erythematous nodules and plaques
- Usually on anterior shins *
- Often idiopathic, but can be assoc w/ sarcoidosis, coccidioides, histoplasmosis, TB, strep infections, leprosy, and Crohn's
- Peak age 20-30
- 1-15 cm in size
- Rarely ulcerate
Erythema nodosum
195
- Papules and plaques with silvery scaling
- Common on knees and elbows
- Koebner phenomenon – lesions develop along site of injury
- Auspitz sign – pinpoint bleeds when scales are scraped off
- Woronoff's ring
- Acanthosis with parakeratotic scaling (nuclei still in stratum corneum)
- Club-shaped rete ridges
- Absent granular layer
- Assoc w/ nail pitting and psoriatic arthritis
- HLA-B13
Psoriasis
196
- Subtype of psoriasis
- Sterile sheets of pustules on an erythematous base
- Localized or generalized
- Painful with fever
Pustular psoriasis
197
- Subtype of psoriasis
- Children and young adults
- Post-streptococcal infection
- Trunk with sparing of palms and soles
Guttate psoriasis
198
- MC ages 55-60
- Local radicular pain 2-3 days prior to eruption
- Steel-gray nuclei, multinucleated cells with eosinophilic intranuclear inclusions *
Herpes zoster (VZV)
199
- Branny, greasy red scale on scalp / face / chest / penis
- P. ovale infection
- Abnormal immune response to P. ovale with normal amt of yeast
- Free fatty acid release
- M > F
- All races, puberty to adulthood
Seborrheic dermatitis
200
- Corynebacterium minutissimum infection (G+ rod) affecting the intertriginous areas (toes/groin/axilla)
- Red/brown scaly macules with an erosive collarette-like scale
- WOOD'S LAMP
- Chronic
- Assoc w/ diabetes
Erythrasma
201
- Pruritic, planar, polygonal, purple papules and plaques (6P's) *
- Often with reticular white lines on their surface (Wickham's stria)
- MC on wrists, elbows, and oral cavity (oral = Wickham's stria)
- 'Saw-tooth' appearance on histo *
- Assoc w/ chronic hep C *
Lichen planus
202
- Rose or pink-colored scaly patches or thin plaques
- Increase in CD4 and Langerhans cells in dermis
- "Herald patch" following days later by "Christmas tree" distribution *
- Multiple plaques with collarette scale
- Self-resolving in 6-8 weeks
Pityriasis rosea
203
- Tinea corporis
- Superficial infection of skin
- Trichophyton, Microsporum, Epidermophyton
- Anthropophilic, zoophilic, geophilic
Dermatophyte infection
204
- Reddish-orange scaling plaques of unknown etiology
- Keratoderma on palms and soles and follicular keratotic papules
- AD
- Similar features of vitamin A deficiency
- 5 subtypes
Pityriasis rubra pilaris
205
- Subtype of pityriasis rubra pilaris
- Classic adult type (MC)
- Red-brown plaques with "islands of sparing"
Type 1 pityriasis rubra pilaris
| "Classic adult"
206
- Subtype of pityriasis rubra pilaris
- Adult atypical type
- Ichthyosiform
Type 2 pityriasis rubra pilaris
| 'Adult atypical"
207
- Subtype of pityriasis rubra pilaris
- Classic juvenile type
- Similar to type 1, but before age 2
Type 3 pityriasis rubra pilaris
| "Classic juvenile"
208
- Subtype of pityriasis rubra pilaris
- Circumscribed juvenile type
- Well demarcated follicular hyperkeratosis along the elbows and knees
Type 4 pityriasis rubra pilaris
| "Circumscribed juvenile"
209
- Subtype of pityriasis rubra pilaris
- Atypical juvenile type
- Prominent follicular hyperkeratosis with scleroderma-type changes on the palms and soles
Type 5 pityriasis rubra pilaris
| "Atypical juvenile"
210
- Subtype of pityriasis rubra pilaris
- HIV type
- Orange-red plaques with follicular hyperkeratosis and "islands of sparing"
- Skin, mucous membranes, nails, eyes
Type 6 pityriasis rubra pilaris
| "HIV type"
211
- Scaling plaques which mimic eczema
- Itchy
- Multiple different shades of red-brown
- Round, oval annular, or bizarrely shaped
- Check for LAD
- Affects the CD4 T helpers
- Lymph nodes and organs become involved
- > 50
- Males
- Assoc w/ HTLV
Cutaneous T-cell lymphoma
212
- Scarring atrophic photosensitive dermatosis
- Erythematous papule or plaque with modest amt of scale
- Hypo- or hyperpigmented
- Mucosal, palms and soles
- 1:2 (M:F)
- Ages 20-40
- Genetic predisposition
- Heat shock protein induced by UV light
- Mostly asymptomatic, mild itching
- Look for pericarditis, neurologic sx
- Malignant transformations (SCC) can occur
Discoid lupus erythematosus
213
Drug eruption:
| Over-dosage of coumadin...
Purpura
214
Drug eruption:
| Accumulation of silver nitrate
Argyria
215
Drug eruption:
| Phototoxic...
Doxycycline
216
Drug eruption:
| Imbalance of normal flora with ATB
Candidiasis
217
Drug eruption:
| Killing of bacteria or fungus by appropriate agent causes:
Jarisch-Herxheimer rxn
218
- Very superficial skin infection
- Usually from S. aureus or S. pyogenes
- Highly contagious
- Honey-colored crusting *
- Common on face, but can be anywhere
Impetigo
219
- Exotoxin destroys keratinocyte attachments in the stratum granulosum only (vs. toxic epidermal necrolysis, which destroys at epidermal-dermal junction)
- Characterized by fever and generalized erythematous rash
- Sloughing of upper layers of the epidermis that heals completely
- Seen in newborns and children (nurseries and daycare)
- (+) Nikolsky sign
Staphylococcal scalded skin syndrome
220
- IgG (IgG1 and IgG4) against desmoglein (desmosomes)
- Acantholysis >> flaccid intraepidermal bullae
- (+) Nikolsky sign
- (+) Asboe-Hansen sign (lateral pressure on the bulla will spread bulla the uninvolved skin)
- Assoc w/ myasthenia gravis and thymoma
Pemphigus vulgaris
221
- Asymptomatic to painful
- Prodrome = itching/burning
- Recurrent lesions common
- "Vesicular or ulcerative on an erythematous base"
- Oral, genital, body, keratoconjunctival, encephalitis, anal
Herpes simplex
222
- "Oval teardrop on an erythematous base" *
- "Dew drop on a rose pedal" *
- Itchy rash
- Face, trunk
- 10-21 day incubation
```
Chicken pox
(HSV-3 – varicella)
```
223
- Less severe than pemphigus vulgaris
- IgG against hemidesmosomes (epidermal BM – "bullow" the epidermis) *
- TENSE bulla containing eosinophils *
- Spare oral mucosa *
- (–) Nikolsky sign
Bullous pemphigoid
224
- Idiopathic photodermatoses from sun exposure (30 min after)
- Papule, vesicles and plaques
- 75% American Indian
- Females (MC)
- Type IV hypersensitivity (delayed-type)
- UV-A-induced ICAM-1
- Spring, lessens throughout summer
Polymorphous light eruption
225
- Pruritic papules, vesicles, and bullae
- Often found on elbows
- IgA at tips of dermal papillae *
- Assoc w/ celiac disease (pts have gluten sensitivity) *
- HLA-B1, B8, DR8, DRQ
- Rx: dapsone
Dermatitis herpetiformis
226
- Assoc w/ infections (e.g., Mycoplasma pneumoniae, HSV*), drugs (e.g., sulfa drugs, B-lactams, phenytoin, allopurinol), cancers, and autoimmune dz
- Mucosal involvement
- Classically seen as target lesions *
- Iris-shaped macules or vesicopapules on the palms or soles *
- 50% under 20
- Koebner phenomenon (lesions arising on sites of trauma)
Erythema multiforme
227
- "Extensive full thickness skin detachment"
- Cell-mediated cytotoxic rxn against epidermal cells
- "sheet-like" epidermal loss *
- Prodrome = 1-3 weeks
- > 30% of the body surface area involved (
Toxic epidermal necrolysis
228
Risk factors for skin cancer?
- contact carcinogens (bruns, chimney soot)
- **sunlight (290-320 nm, >3 burns)
- tanning beds (UV-A)
- UV light (pyrimidine dimers-->C-T mutation)
- Genodermatoses (recessive)
229
Women who use tanning beds are ___% more likely to develop skin cancer
55
230
Screening for cancer:
- Importance?
- ALL skin surfaces
- Self: Monthly if 30-40yo
- Physician too! annually
self-exam minimizes late-stage findings esp in high risk pts (work outside, genetics)
231
```
TQ
Why is it important to recognize skin types?
Ex:
I always burns, never tans
2 always burns, minimal tan
3 Burns often, tans gradually
4 Burns minimally, tans well
5 Burns rarely, tans profusely
6 Never burns, deeply pigmented
```
-Incidence of skin cancer is directly related to potential to burn!
232
- arises from epidermal keratinocytes
- usually in fair-skinned ppl w/ excessive sun exposure
- Men>women
- HPV incr risk
squamous cell carcinoma
233
- usually on sun exposed areas
- Red, indurated papule
- actinic keratosis
- older pts
What are some precursor lesions of this skin cancer?
(squamous cell carcinoma)
- **Bowen's dz (in situ)
- cutaneous horn
- chronic ulcers
- scar tissues
- radiodermatitis
234
How do we dz and treat squamous cell carcinoma?
- biopsy: punch, shave, excision
| - tx: cryosurgery, excision, topical chemo (5-FU), systemic chemo (5-FU, cisplastin) if mets
235
- arises from immature pluripotential cells of epidermis
- slow growing, shiny, pink papule w/ telangiectasias-->ulcerates w/ rolled borders
- sun-exposed areas usually
- older pts
- 70% of nonmelanomas
what is this carcinoma assoc with?
(Basal cell carcinoma)
Assoc with basal cell nevus syn, bazex's syn, and genodermatoses
236
Tx of basal cell carcinoma?
Biopsy first!
- Excision
- Mohs sx (mowing lawn...one way then another)
- Electrodessication: fry off
- Cryosurgery
- Laser tx
(If reccurence then repeat or add radiation/chemo)
237
- avg onset 57 yo but seen in 20-30s
- male>female
- less common in blacks, asians, hispanics
- closer to equator=higher
risk-arm presentations (men's left, women's right)
melanoma
238
TQ
Dysplastic nervus syndrome is a risk factor for melanoma
What is the inheritance pattern of dysplastic nervus syn??
Autosomal dominant!
multiple family members affected
239
Other risk factors for melanoma:
- _____ ______: scaly, rough, erythematous patches on sun exposed areas
- May progress to SCC and melanoma
- Topical 5-FU
actinic keratosis
240
What are the four types of melanoma?
- Superficial spreading
- Nodular
- Lentigo maligna
- Acral lentiginous
241
- MC variety of melanoma
- Arises in pre-existing nevus
- Slowly changes
- Nothing or indentation of perimeter
Superficial spreading melanoma
242
- 2nd MC melanoma
- More aggressive
- Blue-black color and faster growth
- Raised/dome shaped
- Lack horizontal growth (deep)
Nodular melanoma
243
- Uncommon melanoma
- Low potential for mets
- Older white women
- Large (>cm)
- Sun related changes
- Borders convoluted with prominent notching and indentation
```
Lentigo Maligna (Hutchinson's freckle)
"see on grandma's face"
```
244
TQ
- palms of hands, soles of feet
- **nail beds (subungual melanoma)
- non-whites!!!
- older pts
- disorganized array of color
Acral lentiginous (acral means tips/ends)
245
In transit metastasis: nodules representing deposits of melanoma as it spreads to LN
Sign of what?
Metastasis or reoccurrence
246
Pt presents with slate gray appearance
disseminated melanoma (melanosis)
247
TQ
| How do we stage melanoma?
-Determine the depth!
(breslow's thickness)
Entire lesion measured
-thin has much better prognosis than thick:
Thin (4.0 mm) have less than 20% dz free at 5 yrs
248
Melanoma pts are grouped into AJCC stage by ____ status (thickness, LN, mets)
```
LN status with melanoma:
-Males, over 50 w/ thick melanoma
-ulceration
-dx post biopsy or lymphadenectomy
Mets:
-separation b/t local mets and distant mets (organs)
-mets to lung are a unique subset
CATCH EARLY
```
TNM status
249
TQ
| Most important feature of melanoma?
Thickness!!
250
Surgery for melanoma:
- wide local excision + normal tissue
- may have satellite focus
- survival correlates with ________
thickness
251
Surgery for melanoma:
- in situ: ____ cm normal skin
- 4mm thick: __ cm normal skin
- fingers/toes: amputation
- sole of foot: wide excision but save weight bearing tissue (heel, ball)
- ear: wedge or partial amputation (vanGogh)
- face: 1 cm :)
- in situ: 0.5-1.0 cm normal skin
| - 4mm thick: 3.0 cm normal skin
252
What is the only curative modality for nodal melanoma mets?
| -risk for mets incr wtih thickness, ulceration, and location (foot, hand, scalp, face)
LN dissection
253
T/F All pts with melanoma 1 mm in breslow thickness should undergo sentinel LN biposy and dissection
True!
254
T/F
| Melanoma can be treated with radiotherapy
FALS
Eradioresistant
-use if painful bony mets or brain mets
255
Systemic therapy for melanoma?
- melanomas >4mm OR
- in transit mets OR
- regional LN mets
alpha interferon given in high dose then 3x/wk for 1 yr
- SE significant
- improves survival by 25%
256
Systemic therapy for melanoma?
-DTIC, Adriamycin, Cisplatin, Vinca alkaloids, taxanes
-Immunotherapy involves what?
Alpha IFN
IL-2
Tumor vaccines
257
Metastatic melanoma tx that require patient selection due to SE?
-_________: monoclonal Ab targeting CTLA-4-->
immune reaction against tumor-_________: BRAF kinase inhibitor, cutaneous toxicity
Ipilimumab
Vemurafenib
258
TQ
Which metastatic melanoma tx is actually well tolerated???
Which patient population?
Dabrafenib...drug inhibit BRAF in pts with V600E mutation of BRAF (fever, hypergly)
259
TQ
SE of BRAF inhibitors used for melanoma is due to what? What are the SE?
Activation of MAP kinase pathway: bypasses inhibition of BRAF-->
- SCC and keratoacanthomas
- **Cutaneous: rash, photosensitivity, alopecia
- QT prolongatoin (CYP34A)
260
TQ
- New tx for melanoma that initially is approved for BRAF mutant melanoma as a MEK inhibitor
- approved for use in combo with dabrafenib
Trametinib
| combo of dabrafenib + trametinib way better but may cause fever!
261
- Primary cutaneous neuroendocrine carcinoma (small blue cells)
- Arises from cells in basal layer of epidermis and hair follicles
- Rapidly growing, bluish red
- highly malignant (mets early)
- very rare: fair elderly pts, women do better
Merkel cell carcinoma
262
Tx of merkel cell carcinoma?
- wide excision and prophylactic LN dissection
| - chemo if metspoor prognosis :(
263
- bone marrow derived dendritic cells in the upper layer of epidermis
- limited to one organ system (bone 77%)
- benign but may be aggressive
- often treated with chemo agents
Tumors of langerhans cells
264
TQ
- Brown to purplish papules (Hashimoto-Pritzker variant rash)
- Eczemtous rash (looks like candida)
- Oral lesions
Tumors of langerhans cells (LCH)
265
Tx of LCH?
Topical therapy if single system
Multisystem=chemo if symptomatic
INCURABLE
266
TQ
- single or multiple small nodules on face and neck resembling warts
- Cowden's syndrome
- malignant lesions rare (carcinoma form)
- local resection establishes dx and is curative when malignant
Trichilemmoma (benign) tumor of hair follicle
267
-may be single (nonhereditary) or multiple (autosomal dominant
)-appears as skin colored papules on nasolabial folds, eyelids, and central face
-may be confused with BCC
-local resection curative
Trichoepithelioma tumor of hair follicle
268
- tumors arising from the hair matrix
- single or multiple
- invade locally but no mets
- local resection curative
Pilomatricoma tumor of the hair follicle
269
- small, yellowish papules on the vermillion border of the lips or oral mucosa
- ectopic sebaceous glands
- incr w/ age
- Retier's syndrome assoc
- not malignant
Fox-Fordyce Anomaly
(tumor of sebaceous gland)
(Fordyce's spots)
270
-occurs MC in the conjunctiva of the upper eyelids in women 60-80 yrs old-asians-slow but aggressive and mets
Sebaceous carcinoma
271
- benign tumor of eccrine glands
- airse from outer cells of the intraepidermal duct
- pendunculated and skin colored
- sole of foot, palm of hand
- surgical excision
Poroma (benign tumor of eccrine glands)
272
- benign tumor arising from intradermal coiled duct of eccrine gland
- multiple, firm, smooth, dome-shaped movable pink to red papules
- Turban
- female>male
- rarely-->carcinoma
- surgical excision
Cylindroma ("turbon tumor") (benign tumor of eccrine glands)
273
- solitary eccrine gland carcinoma
- tumor of face, head, hand, or foot
- mets
- differentiate from other primary cancers
Clear cell carcinoma
274
- englarging, ulcerated nodule
- eccrine gland carcinoma
- highly malignant
- differentiate from mets from other sites
Eccrine Adenocarcinoma
275
TQ
- low grade lymphoma of T cells in skin
- shed lymphoma cells into blood (sezary syndrome)
- CMV IgG serology
- tx with topical nitrogen mustard, PUVA, electron beam radiology
Cutaneous T cell lymphoma
(mycosis fungiodes)
(lymphoreticular tumor)
276
- benign vascular tumor that mimics the modified smooth muscle cells of glomus body (AV anas in skin)
- small, blue-red nodule in subcutaneous tissue or subungual region of finger
- PAIN
Glomus tumor
277
TQ
- malignant tumors of blood or lympatic vessels
- Assoc with Stewart-Treves Syndrome!!!
Angiosarcoma
278
TQ What is Stewart-Treves syndrome?
| (assoc with angiosarcoma)
- Cutaneous lymphangiosarcoma arising in chronic lymphadematous extremities
- seen in breast cancer
279
-benign lesions common in children
-spontaneously regress!!
dont cut-rapid growth
Hemangioma
280
Cavernous hemangioma: multiple large dilated vessels with flattened endothelium
Risk of what?
DIC
281
- malignant vascular lesion in skin of lower extremities
- mediterranean or jewish
- mets to lung and GI tract
- local excision and radiation
Kaposi's sarcoma classic type
(African type in Bantu men in Africa, children, aggressive
Immunocompromised type in HIV, organ transplant pts)
282
-MC of all benign neoplasm
s-anywhere where fat is present
-fat cells
-no tx needed
lipoma
283
- malignant tumor arising from fat
- 55-60 yo-2nd MC soft tissue sarcoma
- aggressive surgery!!
- radiation and chemo (mets)
Liposarcoma
