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

[image]

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[image]

Mott cells[image]

Cytoplasmic/nuclear inclusions:

fibrils, crystalline rods

Russell bodies (=Dutcher bodies in cytoplasm)[image]

Dutcher body (nucleus)[image][image]

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

[image]

-glomangioma= variant that resembles cavernous hemangioma

[image][image]

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[image][image]
• 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)

[image]

Clara cell granules[image]

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

[image][image]

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-