Case 2 -

Mucinous Tubular and Spindle Cell Carcinoma of the Kidney David Grignon Wayne State University Detroit, MI

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Clinical History A 70 year old man was found to have mass involving the right kidney during work up for right upper quadrant pain. There was no significant past history. A radical nephrectomy was performed. The gross description from the pathology report indicated that the kidney contained a "2.0 x 2.0 x 1.8 cm white-grey, fleshy tumor. It is located within the center of the specimen, and appears to involve part of the cortex and an entire pyramid." Case 2 - Figure 1 - Mucinous tubular and spindle cell carcinoma. Low power photomicrograph illustrating the sharp circumscription of the tumor from the adjacent kidney. Case 2 - Figure 2 - Mucinous tubular and spindle cell carcinoma. Intermediate power photomicrograph illustrating the tightly packed tubules with many having long open tubular profiles. Case 2 - Figure 3 - Mucinous tubular and spindle cell carcinoma. Intermediate power photomicrograph highlighting the tubules some of which are collapsed without apparent lumens. Case 2 - Figure 4 - Mucinous tubular and spindle cell carcinoma. High power photomicrograph illustrating the tubules. Note the prominent basal lamina around the tubules. Discussion The broad area of tumors of collecting duct derivation is undergoing considerable change and redefinition [Srigley, 1998]. Most urologic pathologists have taken to restricting the term "collecting duct carcinoma" to the classically described, high grade tumor with papillary ductal architecture and stromal desmpolasia. The tumors that develop in association with sickle cell trait are dealt with separately under the term medullary carcinoma [David, 1995; Swartz, 2002]. An initial report of low grade collecting duct carcinoma included at least 2 distinct tumors and these have now been assigned nomenclature of their own ( mucinous tubular and spindle cell carcinoma and tubulocystic carcinoma). It must be appreciated that that this area will continue to mature in the coming years. The most current classifications of renal tumors, scheduled to be published early in 2004 represent an extension of the 1997 consensus classification [Störkel, 1997] and include neoplasms recently defined on both morphologic and cytogenetic grounds. Mucinous tubular and spindle cell carcinoma is on such entity. Tubulocystic carcinoma is just in the process of being defined (one abstract at this meeting presented a series of cases [Amin et al]) and is not included in these classifications but likely will emerge in future classifications as a distinct entity. A coordinated effort was made to bring the 2003 WHO classification [Eble, 2004] and that presented in the 4th edition of the AFIP fascicle in line [Murphy, 2004]. Classification of Renal Cell Carcinoma (AFIP 4th Ed) Clear cell Multilocular cystic Papillary Chromophobe cell Collecting duct Medullary Mucinous tubular and spindle cell Xp11.2 associated carcinomas Unclassified The original paper on low-grade collecting duct carcinoma of the kidney included tumors that now are now designated mucinous tubular and spindle cell carcinoma [MacLennan, 1997]. This uncommon pattern of RCC that has been postulated to be of collecting duct and possibly loop of Henle origin. It occurs predominantly in females and in middle age[Parwani, 2001; Hes, 2002; Srigley, 2002; Rakozy, 2002]. Most cases are single though multifocality has been described. An association with nephrolithiasis was identified in 3 of 11 cases reported by Hes et al. [2002]. In one series a single case had a documented regional lymph node metastases [Hes, 2002] indicating the potential for malignant behavior, though information is limited. Grossly, mucinous tubular and spindle cell carcinomas are solid, pale tan to yellow, to gray-white lesions that may have slight focal areas of necrosis or hemorrhage. Histologically, they manifest elongated branching tubules in a bubbly myxoid stroma. The collapsed tubules result in a cord-like pattern and spindle cell areas are also present. The tubules are striking with characteristic long profiles. The basal lamina, around the tubules, is highlighted by PAS staining. The cells are cuboidal with scant, clear to pale, acidophilic cytoplasm and low-grade nuclear features. The background is mucinous with basophilia and a characteristic bubbly appearance. Immunohistochemical studies have had widely varied results, but most tumors express pan cytokeratins, CK7, CK18, CK19 and 34ßE12. EMA is positive in the majority with less frequent positivitiy for vimentin and CD15. Ulex europus is positive in most. [Parwani, 2002; Rakozy, 2002; Srigley, 2002]. Although the pattern generally supports a collecting duct origin, the results are very inconsistent. Ultrastructurally the tumor consists of collapsed tubules with the lining epithelial cells having a simple appearance with scattered, short microvilli on the surface reminiscent of the loop of Henle. The "spindled" areas reflect these collapsed tubules with no visible lumens. Cytogenetic studies have demonstrated consistent losses involving chromosomes, 1, 4, 6, 8, 9, 13, 14, 15 and 22, supporting this lesion as being a distinctive entity [Rakozy, 2002; Srigley, 2002]. Tubulocystic Carcinoma In the 3rd series AFIP fascicle, Farrow [1994] illustrated an unusual tumor with a multicystic gross appearance and striking mixture of tubules and micro/macro cysts histologically. Similar cases were subsequently included in the low-grade CDC paper [MacLennan, 1997]. We have seen a large number of cases now that are remarkable for the uniformity on gross and microscopic characteristics [Amin, 2004]. The tubules and cysts are lined by cuboidal to columnar cells with eosinoiphilic cytoplasm. Nuclei are uniform and contain nucleoli. In our experience approximately 10% metastasize. Whether these truly derive from the collecting system is uncertain. References Davis CJ Jr, Mostofi FK, Sesterhenn IA. Renal medullary carcinoma: The seventh sickle cell nephropathy. Am J Surg Pathol 1995; 19:1-11. Eble JN, Sauter G, Epstein JI, Sesterhenn IA (Eds). World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press. Lyons, 2004 Hes O, Hora M, Perez-Montiel DM, et al. Spindle and cuboidal renal cell carcinoma, a tumor having frequent association with nephrolithiasis: report of 11 cases including a case with hybrid conventional renal cell carcinoma/spindle and cuboidal cell renal cell carcinoma components. Histopathology 2002;41:549-555. MacLennan GT, Farrow GM, Bostwick DG. Low-grade collecting duct carcinoma of the kidney: Report of 13 cases of low-grade mucinous tubulocystic renal carcinoma of of possible collecting duct origin. Urology 1997; 50:679-684. Murphy WM, Beckwith JB and Farrow GM. Tumors of the kidney, bladder, and related structures. Washington: Armed Forces Institute of Pathology, 1994: 3rd series. Murphy WM, Perlman E and Grignon DJ. Tumors of the kidney, bladder, and related structures. Washington: Armed Forces Institute of Pathology, 2004: 4th series. Parwani AV, Husain AN, Epstein JI, Beckwith JB, Argani P. Low-grade myxoid renal epithelial neoplasms with distal nephron differentiation. Hum Pathol 2001; 32:506-12. Swartz MA, Schneider DT, Rodriguez R, Beckwith JB, Perlman EJ. Renal medullary carcinoma: clinical, pathologic, immunohistochemical, and genetic analysis with pathogenetic implications. Urol 2002;60:1083-9. Srigley JR, Eble JN. Collecting duct carcinoma of kidney. Semin Diagn Pathol 1998;15:54-67. Srigley JR, Kapusta L, Reuter V, Amin MB, Grignon DJ, Eble JN, Weber A, Moch H. Phenotypic, molecular and ultrastructural studies of a novel low-grade epithelial neoplasm possibly related to the Loop of Henle. Mod Pathol 2002; 15:182A [abstract] Störkel S, Eble JN, Adlakha K, Amin M, Blute ML, Bostwick DG. Classification of renal cell carcinoma: Workgroup 1. Cancer 1997; 80:987-989.