Final Diagnosis -- Collecting duct carcinoma


Collecting duct carcinoma


The overall morphologic and immunohistochemical features of this case support a diagnosis of collecting duct carcinoma (CDC). The differential diagnosis in this case includes a high-grade papillary renal cell carcinoma (RCC), and mucinous tubular and spindle cell carcinoma (MTSC). In particular, the presence of immunohistochemical staining for ulex europaeus-1 and absence of staining for racemase argue against papillary RCC and MTSC. In addition, the high-grade nuclear features and lack of predominating elongated tubules or definite spindle cell component argue against a diagnosis of MTSC. Regarding the patient's lung nodules, a subsequent fine-needle aspirate of the lung and hilar lymph node biopsy showed evidence of metastatic carcinoma favoring renal origin.

CDC is a rare, aggressive, high-grade neoplasm which arises from the renal medullary collecting ducts and from an embryologic standpoint, the mesonephros. It was previously subgrouped with the RCCs by the World Health Organization (WHO) in 1981 with the alternative name "Bellini duct carcinoma," but has since been recognized as a separate entity. It accounts for approximately 0.6-3.0% of all renal epithelial neoplasms, and occurs in patients in their second-fifth decades (average age 55 years) with a slight male preference (M:F 1.7-2:1). At the time of initial presentation, approximately 40% of patients have metastatic disease and may have generalized inflammatory symptoms (e.g. fever, general malaise, weight loss), flank pain, and a history of intermittent hematuria as this patient demonstrated.

Radiologically and grossly, CDC is generally poorly circumscribed and classically occupies a deep, central medullary location. It ranges in size from approximately 1-16 cm. Renal angiography will often show the mass to be hypovascular or avascular. The cut surface is classically firm, gray-white, and sometimes has areas of obvious necrosis. It often involves hilar structures and approximately 20% of cases show renal vein invasion.

Histologically, CDCs have a range of irregular architecture: tubulopapillary, pseudopapillary, cribriform, microcystic, ductal, and solid. The tumor consists of intermixed round-to-oval, clear eosinophilic and basophilic cells. The cytomorphology of the malignant cells is high-grade with marked nuclear atypia, hyperchromasia, prominent single nucleoli, and sometimes numerous atypical mitoses. Intracytoplasmic mucin can also be seen, and sarcomatoid change can be seen as a sign of dedifferentiation. Cells often protrude into lumens in a hobnail pattern. Marked atypia and dysplasia may be seen in adjacent collecting ducts, and there is usually marked desmoplasia often including granulocytes in the surrounding stroma. Prominent vascular and lymphatic invasion are common.

Immunohistochemically, CDC cells are commonly immunoreactive with markers of the distal nephron (ulex europaeus agglutinin-I, peanut agglutinin lectin, e-cadherin, epithelial membrane antigen (EMA)), high molecular weight keratins (34betaE12, cytokeratin 19), and low molecular weight keratins. Cells are usually negative for markers of proximal tubules (CD10, Leu-M1, RCC, N-cadherin, racemase). Vimentin may be present in tumor cytoplasm, and c-kit may also be positive. Aquaporin-3 (AQP-3), present in normal collecting duct and urothelial cells, as well as high-grade urothelial carcinoma, is also present in CDC.

Cytogenetic analyses often demonstrate monosomy of chromosomes 1, 6, 12, 15, 18, 21, and 22. Loss of heterozygosity (LOH) is seen in chromosome arms 1q (similar to urothelial carcinoma, 57-69%), 6p, 8p, 13q, and 21q. Molecular alterations also exist that suggest tumor heterogeneity, including loss of the Y chromosome; gains of chromosomes 7 and 17; and LOH of the von Hippel Lindau gene (3p), p16 (9p), and p53 (17p). In addition, one can see loss of DNA sequences involving chromosomes 1, 2, 9, 11, and 18; gains of DNA sequences affecting chromosomes 12, 16 and 20; and c-erb B2 oncogene amplification (45%).

The differential diagnosis of CDC includes papillary RCCs, medullary carcinoma, conventional RCC, urothelial carcinoma, and metastatic carcinoma. MTSC and tubulocystic carcinoma are also briefly discussed here due to the presence of mucin in this case as well as the overlap of these entities' nomenclature in the past.

Patients with CDC have a poor prognosis, with approximately 2/3 of patients dying within 2 years of the initial diagnosis (mean survival is 11.5 months). Metastases at the time of diagnosis are common in the regional lymph nodes (80%), adrenal glands (25%), lung (25%), liver (20%), and skin. Metastases have also been reported in the leptomeninges and bone which are usually osteoblastic although isolated osteolytic metastases have recently been reported. There is a high frequency of local recurrence and distant metastases even when a radical nephrectomy has been successfully performed. In addition, conventional treatments for renal cell carcinoma including radiation, chemotherapy, and immunotherapy are usually not effective. Recent studies show promising results with chemotherapy usually used for primary urothelial carcinomas, which may suggest biologic similarities between the two tumors.

In summary, this case demonstrates a collecting duct carcinoma in a 52-year-old female with classic symptoms of a renal cell carcinoma and lung metastasis at the time of diagnosis. Some histologic features overlap with those seen in high-grade papillary renal cell carcinoma and mucinous tubular and spindle cell carcinoma. Strong immunohistochemical staining for ulex europaeus-1 helped to make the final diagnosis.


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Contributed by Rashi Singhal, MD, MPH, and Anil Parwani, MD, PhD

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