What are the risk factors and epidemiology of urothelial carcinomas?

List common molecular alterations a/w urothelial cell carcinoma of bladder

Risk factors of Urothelial cell Carcinoma:

**(#1) CIGARETTE SMOKING- 3-7X ↑; 50-80% in smokers

(2) Arylamines - (ie 2-naphthylamine)- usually industrial exposure

(3) Schistosoma haematobium- Egypt, Sudan (7% are SCC)

(4) long term use of Analgesics

(5) long term use of cyclophosphamide

Epidemiology: M>F (3:1); 80% of pts are 50-80 yo

50% are high grade at presentation

most arise from lateral or posterior walls at the bladder base

Molecular alterations-

--monosomy 9 or del 9p and/or 9q- the only genetic abn freq in superficial papillary tumors or flat high grade; specific genes- 9p21 (p16 and p15)- tumor suppressior genes

-INVASIVE lesions a/w 17p (p53) del/mut; 13q deletions (Rb gene); 14q (unknown gene)

List grading and staging characteristics of urothelial cell carcinoma

Grading of TCC/Urothelial carinoma:

-Urothelial papilloma (1% of total, younger patients, papillary fronds with    epithelial cells that are histologically identical to normal)

-Urothelial neoplasm of low malignant potential (some cytologic and architectural atypia. Rare mitosis, only slight loss of polarity, 95% 10 year survival)

-Low grade (Increase cell layers >7, greater atypia, low risk of progression, may be invasive 10%, 50% recur)

-High grade (more anaplastic changes, mitosis, loss of polarity. Tend to be invasive: 80%,  If deeply invasive 40% metastatic, 90% recur, 65% 10 year survival).  High grade lesions may be flat or papillary. May show squamous differentiation.

Staging: based on depth of invasion-

-pTX:   Primary tumor cannot be assessed

-pT0:    No evidence of primary tumor

-pTa:    Noninvasive papillary carcinoma

-pTis:   Carcinoma in situ: “flat tumor”

- pT1:    Tumor invades subepithelial connective tissue (lamina propria)

-pT2: Tumor invades muscularis propria (detrusor muscle)

        pT2a:  Tumor invades superficial muscularis propria (inner half)

pT2b:  Tumor invades deep muscularis propria (outer half)

-pT3: Tumor invades perivesical tissue

        pT3a:  Microscopically

        pT3b:  Macroscopically (extravesicular mass)

-pT4: Tumor invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall

        pT4a:  Tumor invades prostatic stroma or uterus or vagina

        pT4b:  Tumor invades pelvic wall or abdominal wall

**side note-

Squamous cell carcinoma of bladder- NO papillary or transitional areas; is MUCH more aggressive/invasive; 30% 1-yr survival; much worse than UCC

Adenocarcinoma of the bladder: rare, arise from urachal remnants; small cell, signet rings, or mixed adeno/TCC

Schistosoma egg species-

Identify these eggs and describe

A                B                    C

A= S. mansoni -ellipsoid; morphologically distinctive d/t prominent lateral spine; size 114-180 μm x 43-75 μm

B= S. haematobium -ellipsoid; morphologically distinctive d/t delicate, terminal spine; size 112-170 μm x 40-70 μm

C=S. japonicum -smaller than S. mansoni and S. haematobium; ovoid; minute lateral knob; size 55-85 μm x 40-60 μm

What is the most common extramedullary site for plasmacytoma?

General characteristics of Plasma cell myeloma- epidemiology; clinical findings

Histology and IHC/flow of plasma cell neoplasms

The most common extramedullary site for plasmacytoma is- NASOPHARYNX

Plasma cell myeloma:

-- MC lymphoid malignancy in blacks, and 2nd mc in whites

--extraosseous PCN= 3-5%

--=15% of all heme malignancies

Clinical:

• PCN- w/ involvement of skeleton and destruction at multiple sites (MM)--> hypercalcemia (triggered by IL-1b and IL-6) [High serum IL-6= poorer prognosis, and a/w HHV-8 -which produces an IL-6 analogue]
• can involve LN's and skin
• production of excess monoclonal Ig with decreased normal Ig- detected by electrophoresis (serum or urine)---IgG-55%; IgA 25%.
• Renal insufficiency in 50% and Bence Jones proteinuria (toxic to tubules) in 60-70%
• Amyloidosis (AL-type)
• hyperviscosity syndrome in 7% of pts secreting IgA or IgG3
• 1% of myelomas do not secrete Ig
• may have pancytopenia with extensive marrow involvement
• Rarely- plasma cells flood the PB--> plasma cell leukemia
• 50-70% reach a "remission" with median survival 3yrs

Histology:

Flames cells

Mott cells

Cytoplasmic/nuclear inclusions:

fibrils, crystalline rods

Russell bodies (=Dutcher bodies in cytoplasm)

Dutcher body (nucleus)

IHC and molecular:

CD20 neg, CD45 neg, MAY be CD56 + (aberrant)

molecular- del 13q and rearrangement of 14q - typically t(11;14)- same as MCL (10%)

What is the common visceral site (ie extracutaneous) for glomus tumor?

MC extracutaneous site for Glomus tumor is the stomach.

Glomus tumor- benign, exquisitely painful tumor of smooth muscle cells (the GLOMUS BODY= AV anastomosis involved in thermoregulations)

-skin, soft tissue and GI tract involved

-most commonly- distal part of digit (under the fingernail)

-branching vascular channels in stroma, consisting of aggregates, nessts and masses of glomus cells

-glomangioma= variant that resembles cavernous hemangioma

MUCIN is present in all of the following except:

A. Appendiceal carcinoid

B. BAC

C. Clear cell Renal cell carcinoma

D. Prostate carcinoma

Review features of appendiceal carcinoid and BAC

Answer:  Mucin is present in all of these EXCEPT: Clear cell renal cell carcinoma- the cleared out spaces are glycogen

Appendiceal carcinoid- =85% of all appendiceal neoplasms- (however, most carcinoids are in small intestine -40% w/i 2 ft of IC valve; and 35% of small int carcinoids are multicentric)

-usually incidental findings in appendix

-solid and trabecullar growth patterns

-transmural spread= frequent; 1.5-9% metastasize

• Adenocarcinoid (goblet cell carcinoid): goblet and tubular types; may have mucin lakes
• Duodenal carcinoid: least frequent location for GI carcinoid; 2/3- gastrin secreters; 1/3 have Zollinger-Ellison syndrome (always with mets); MEN-1;
• 15-20% produce somatostatin (always in region of ampulla of vater)- a/w NF-1, very rarely produce somatostatin syndrome= DM, cholelithiasis and diarrhea
• Gastric carcinoids- a/w pernicious anemia and atrophic gastritis

Bronchoalveolar carcinoma: =1-9% of lung cancers; overall 5-yr survival 25% (but 50-75% if solitary lesion=not typical; 45% metastasize

-tumor cells line alveolar spaces (lepidic growth); abundant mucinous secretions; by definition- not invasive (o/w is called adenocarcinoma)

-contain lamellar bodies, mucin and clara cell granules (NOT argentaffin granules- as is not neuroendocrine)

Clara cell granules

What is the IHC profile of chordoma?

describe chordoma fx

IHC of chordoma= S-100+, CK+, EMA+, VIMENTIN+; only rarely CEA+

Chordoma: derived from notochord; ALWAYS MIDLINE!; malignant; MALES>females; older pts (>30yrs)

- locations- base of skull and cervical spine (37% at clivus); sacrum (50%)- almost always extends into presacral space

- may progress to high grade spindle lesion

-soft lobulated gray tumor appears mucoid

-Histology: lobulation, myxoid matrix, vacuolated cells in chording arrangement

      -chondroid chordoma: purely chondroid and arise in the clivus ONLY, much better prognosis

What is the most common location of hepatoid adenocarcinoma?

Names other types of hepatoid carcinoma

The MC location of hepatoid adenocarcinoma= stomach

-Hepatoid adenocarcinoma of stomach- rare variant, portions of tumor are typical adenocarcinoma- and other areas resemble liver- even to the extent of BILE production and AFP+

others:

-Hepatoid ovarian cancer- pure hepatoid

-hepatoid yolk sac tumors (mixed)

What is the precise translocation a/w Follicular lymphoma (and some DLBCL)?- and the genes involved

t(14;18)(q32;q21)

-BCL-2 gene on 18q21 : Ig heavy chain (14q32)

-seen in most but not all follicular lymphomas

Follicular lymphoma- painless adenopathy, indolent; median survivak 7-9 yrs

-Histologic transformation occurs in 30-50%--> DLBCL

-Composed of small centrocytes and varying # large cells (centroblasts)

-follicular architecture (or diffuse variant- only if low-grade)

-CD10+, CD5-