Answer: C. Clear cell sarcoma of the kidney

Histology: This is a fairly uniform neoplasm composed of spindle to epithelioid cells with inconspicuous cytoplasm and prominent clear extracellular matrix material, simulating the appearance of clear cytoplasm. Cells are separated by regular branching capillary vasculature. At the edge of the lesion, the neoplasm entraps single nephrons. The cytology of the nuclei is bland, with open chromatin associated nuclear grooves. These are the typical features of clear cell sarcoma of the kidney. The patient age in this case is more typical of congenital mesoblastic nephroma, but CCSK can occur in this age group.

Discussion: Congenital mesoblastic nephroma is divided into classic (fibromatous like) or cellular (fibrosarcoma like) types. Aside from differences in cytology, classic CMN has a widely infiltrative broader, whereas cellular CMN is typically associated with high mitotic activity and necrosis. Rhabdoid tumor of the kidney typically features a characteristic cytologic triad; vesicular chromatin, prominent nucleus, and hyaline cytoplasmic inclusions. Rhabdoid tumor of the kidney demonstrates loss if INI1 protein.

Clear cell sarcoma of the kidney is characterized by internal tandem duplication of the BCOR gene in the majority of cases. Approximately 5-10% of CCSKs harbor the recurring chromosome translocation t(10;17) (q22;p13), resulting YWHAE-FAM22 gene fusion. The same gene fusion is also found in a subset of high grade endometrial stromal sarcomas.

Answer: A. Schwannoma

Histology: This is a bland but cellular spindle cell neoplasm centered in the gastric wall. There is an associated lymphoid cuff at the edge of the lesion. The neoplastic cells demonstrate angulated, tapering nuclei with palisading which can be seen in either GIST or schwannoma. In this case, the neoplasm was negative for CD117 and diffusely immunoreactive for S100 protein, supporting the diagnosis of schwannoma. The prominent lymphoid cuff surrounding gastric schwannomas is a clue to the diagnosis and helps distinguish them from GIST

Discussion: GIST would label for CD117 and not diffusely for S100 protein. Leiomyosarcomas and leiomyomas would demonstrate for immunoreactivity for desmin, and would feature more plump spindle cells with abundant eosinophilic cytoplasm and cigar shaped nuclei.

Answer: D. Clear cell carcinoma

Histology: The majority of this tumor has the appearance of a high grade renal cell carcinoma with prominent eosinophilic cytoplasm. This is a highly non-specific appearance, and may be seen in the high grade portions of a wide variety of primary renal tumors. The key in such cases is not so much a broad immunohistochemical panel (which is expensive) but rather thorough sampling of the neoplasm. Additional sections from this case revealed a lower grade area which is typical of clear cell renal cell carcinoma, in that it has a thin capillary vasculature and epithelioid cells with water clear cytoplasm. This area demonstrated diffuse immunoreactivity for carbonic anhydrase 9 (CA-IX), supporting the diagnosis of clear cell carcinoma. Hence, this case is a high grade clear cell RCC.

Discussion: As mentioned above, a large number of renal tumors can have a high grade eosinophilic appearance, and when such nested tumors degenerate the pseudopapillae mimic the true papillae of papillary renal cell carcinoma. The diagnosis of “type II papillary renal cell carcinoma” is always somewhat suspect, as many tumors can acquire this appearance in their high grade areas. Collecting duct carcinoma should be centered on the renal medulla, and demonstrate a high grade infiltrating adenocarcinoma appearance with prominent desmoplastic, inflamed stroma. Renal medullary carcinomas have a more extensive rhabdoid appearance, are associated with INI1-loss, and typically occur in young patients with sickle cell trait.

Answer: C

Microsopic description: Areas of the tumor are composed of just thin capillaries as can be seen in clear cell renal cell carcinoma without identifiable intervening tumor cells. Other areas show large individual cells with abundant pink cytoplasm. Nuclei are ovoid and elongated with delicate chromatic and small nucleoli.

Discussion: There are less than 10 reported cases of hemangioblastoma involving the kidney. Typically, hemangioblastoma involves the cerebellum or spinal cord. More common than in the kidney but still rare, it may also be seen in the adrenal and soft tissue. Hemangioblastomas may be associated with von Hippel Lindau (VHL) syndrome, but is more commonly sporadic. Hemangioblastoma can mimic clear cell renal cell carcinoma as both share the same delicate vascular network. However, in contrast to nests of cells with either clear or eosinophilic cytoplasm, hemangioblastoma contains scattered individual cells with abundant eosinophilic or clear foamy cytoplasm with fine vacuoles that represent lipid. Most the nuclei in hemangioblastoma are benign appearing but there may be some with mild nuclear atypia. Recognition of hemangioblastoma in the kidney requires noting that it is identical to the more common lesions seen in the CNS. Verification of the diagnosis can be made showing the tumor cells are negative for keratin and PAX8, with positivity for inhibin. These lesions are benign with their only significance being their sometimes association with VHL syndrome.

Answer: D

Discussion: Infiltrating bladder tumors with this morphology have been variably described as all of the above choices. The unifying feature is the presence of loosely cohesive cells which lose ecadherin and infiltrate widely in the bladder in a linitis plastic fashion. Some of these tumors resemble infiltrating lobular carcinoma of the breast without plasmacytoid, rhabdoid, or signet ring cytoplasmic features. In a woman it can be hard to rule out spread from a breast carcinoma. GATA3 is not helpful as it is positive in both breast and urothelial carcinomas. GCDFP may help in this differential. In both genders, one also has to put a caveat in the report that a gastrointestinal primary should be excluded. In the current case, the presence of overlying CIS is diagnostic of a primary urothelial carcinoma. The presence of micropapillary features in CIS has no prognostic significance, as opposed to micropapillary features in infiltrating urothelial carcinoma where it adversely affects prognosis.

Answer: B

Histological description: Focally within the TURP specimen there is a focus of crowded dilated glands. The glands are lined by flat and tufted pseudostratified columnar epithelium with nuclei showing visible nucleoli. The cytoplasm is amphophilic.

Discussion: Ductal adenocarcinoma is defined as a variant of adenocarcinoma of the prostate lined by pseudostratified columnar epithelium as opposed to the simple cuboidal epithelium of usual (acinar) prostatic adenocarcinoma. The classic most common patterns of ductal adenocarcinoma are cribriform and papillary and are associated with an adverse prognosis, comparable to Gleason pattern 4 acinar adenocarcinoma. More recently, a new variant of ductal adenocarcinoma has been described where the glands are simple non-cribriform glands resembling high grade PIN. Features that help to distinguish PIN-like ductal adenocarcinoma from high grade PIN is that in the former many of the glands are markedly dilated and often have a flat lining. In contrast, the glands comprising high grade PIN are usually the same size as normal prostate glands. While, there may be focal flat lining to high grade PIN, tufting patterns predominate. Ultimately, the distinction is based on demonstrating a lack of basal cells in PIN-like ductal adenocarcinoma. As a few glands of high grade PIN many lack basal cells in a given plane of section, one needs numerous glands with no basal cells in order to establish a definitive diagnosis of PIN-like ductal adenocarcinoma. PIN-like ductal adenocarcinoma has a relatively favorable prognosis and is graded as Gleason score 3+3=6.