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Year : 2011  |  Volume : 54  |  Issue : 1  |  Page : 127-130
Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma

1 Department of Pathology, Tata Memorial Hospital, Parel, Mumbai - 400 012, India
2 Department of Surgical Oncology, Tata Memorial Hospital, Parel, Mumbai - 400 012, India

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Date of Web Publication7-Mar-2011


Tubulocystic renal cell carcinoma (TCRCC) is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC) and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

Keywords: Kidney tumor, renal carcinoma, tubulocystic renal cell carcinoma

How to cite this article:
Deshmukh M, Shet T, Bakshi G, Desai S. Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma. Indian J Pathol Microbiol 2011;54:127-30

How to cite this URL:
Deshmukh M, Shet T, Bakshi G, Desai S. Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma. Indian J Pathol Microbiol [serial online] 2011 [cited 2022 Aug 11];54:127-30. Available from: https://www.ijpmonline.org/text.asp?2011/54/1/127/77363

   Introduction Top

Renal cell carcinoma (RCC) is composed of a group of genetically, biochemically, biologically, and morphologically diverse neoplasms. [1] The last decade has seen tremendous advances with discovery of unique variants and targeted treatments for RCC. One such variant is a tubulocystic renal cell carcinoma (TCRCC) which was first adequately described by Amin et al. in their abstract on 29 cases of such renal tumors. [2] Following this there are two recent series of 13 and 31 cases including one by Amin et al. describing the morphological and clinical features including the patient outcome for this rare tumor. [1],[2] The two series documented conflicting association of TCRCC with papillary renal carcinoma and this remains an unresolved issue. The tumor has not yet been formally recognized in the recent edition of World Health organization. [3]

We report the youngest patient with tubulocystic carcinoma of kidney with high-grade papillary RCC and lymph nodal metastases with a view to add to the existing attempts at accurate recognition for this tumor.

   Case Report Top

This 18-year-old female presented with lump in abdomen since 6 months. The patient did not have any other complaints. A computed topographic (CT) scan revealed a large heterogeneously enhancing mass arising from the lower pole of the kidney measuring 11.3 x 8.6 x 5.6 cm. Tumor showed few calcified foci within it. Also noted was another lesion with cystic spaces in upper pole of kidney. The left kidney was normal. Multiple enlarged retroperitoneal nodes were seen in the retrocaval, aortocaval, and left para-aortic regions, largest measuring 3.5 x 2 cm in the retrocaval region. All the other investigations like urine microscopy, bone scan, and chest x-ray were unremarkable. Given the high likelihood of RCC with nodal metastases, the patient underwent a radical nephrectomy with retroperitoneal node dissection at some other hospital. The diagnosis of tubulocystic carcinoma associated with a high-grade papillary carcinoma with nodal metastases was rendered on review of the histology at our institute. As local therapy was complete, the patient is under observation. Seven months after her surgery, she did complain of low back ache but thorough radiological work up documented no local evidence of recurrence.

Gross and Microscopic Findings

On gross examination, the kidney measured 19 x 13 x 10 cm and cut surface revealed a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12 x 9 x 9 cm, reaching up to the renal sinus. The upper pole of the kidney showed many clustered small smooth-walled cysts with few solid areas. No renal capsular or vascular involvement was seen. Also received separately were the para-aortic nodes, the largest measuring 4 cm in maximum diameter with a gray white cut surface.

Histological examination of the main tumor showed cystic spaces variable in size and ranging from large dilated cysts lined by flatter epithelium filled with eosinophilic or bluish mucoid secretions to smaller tubular spaces lined by single layer of cuboidal to columnar cells with eosinophilic and sometimes vacuolated cytoplasm [Figure 1]a and d. The nuclei had irregular nuclear membranes and would qualify for a Fuhrman nuclear grade 2. The upper pole lesion showed the typical morphology of a high-grade papillary renal cell carcinoma (PRCC) with cysts lined by complex papillary structures with true fibrovascular cores. Papillary areas with cell showing hybrid features between vacuolated cells of TCRCC and nuclear features of PRCC were also seen. The para-aortic nodes revealed metastases from a high-grade RCC similar in morphology to the PRCC with areas of necrosis.
Figure 1: Histological section from tumor documenting. (a) Dilated cystic spaces filled with blue secretions (H and E, ×200). (b) Tubules with secretory changes. (c) Cysts lined by flattened cells with hob nail like arrangement (H and E, ×100). (d) Areas of papillary renal cell carcinoma with high-grade nuclei (H and E, ×200).

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On immunohistochemistry, the tumor cells in TCRCC expressed CD10, CK19, and CK7 [Figure 2]. The staining was strongest in the areas with intracytoplasmic vacuolization. CK7 staining was absent in PRCC element consistent with its high-grade nature. Both tumors were negative for high molecular weight cytokeratin (HMWCK) and p63.
Figure 2: Immunohistochemistry for CD 10 shows prominent staining in areas of vacuolization (ABC, ×200).

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   Discussion Top

The spectrum of renal carcinomas is expanding with newer histological variants being documented. The histological features and cell of origin of some of these tumors are not yet fully understood due to their rarity and limited studies.

Except for the age, the gross findings, the histological features, and the immunohistochemistry findings of the case under discussion are typical of a tubulocystic carcinoma of the kidney. Although the histological uniqueness of this tumor was recognized by Masson, [2] the first detailed description of tubulocystic carcinoma of kidney came in 1997 when MacLennan et al.[4] described 13 cases which they called as low-grade mucinous tubulocystic renal cancer likely of collecting duct origin due the mucin production within the tumor. As opposed to the highly aggressive collecting duct carcinomas, these had less aggressive behavior and only one patient died of metastatic disease.

Amin et al.[2] and Yang et al., [1] subsequently in their analysis of 31 and 11 cases of tubulocystic carcinomas, adequately reaffirmed the histological features and even documented gene profiling data in these TCRCC. Subsequent studies followed one of which reconfirmed the association of TRCC with PRCC. [5],[6] While the histological findings of this tumor are same across both these studies, the cell of origin and association with PRCC remains controversial. This case report is an attempt to further document association of TCRCC with PRCC in a young girl.

TCRCC typically affects adults in the age range 36-94 years with a strong male predominance (7:1). [3] The present case is the youngest patient with this tumor till date and stresses that this tumor can also occur in adolescent children. While most tumors are solitary, multiple tumors in the same kidney can occur in 30% of patients and such multicentric tumors are often admixed with papillary RCC. [1]

The typical morphology of the tumor is a spongy or ''bubble wrap'' appearance due to the presence of multiple cysts. The histology mimics cystic nephroma, multilocular cystic RCC, oncocytoma with prominent tubules and cysts, and mixed epithelial and stromal tumor of the kidney. [3] The nature of the secretions in a multilocular RCC and the lining epithelium are different. Also the hob nailing observed in TCRCC is not observed in multilocular RCC. Although architecturally ''benign appearing,'' most benign lesions of kidney can be distinguished from TCRCC based on the clearly malignant nuclei with nuclear irregularity and Fuhrman nuclear grade 2 or 3 nuclei. [1],[2]

The morphologic features of these tumors are so distinctive that utilization of immunohistochemical markers is not necessary for diagnostic purposes. [2] However; immunohistochemistry has been the provenience on which cell origin has been postulated in various studies. Immunohistochemical evaluation of cytokeratin in normal kidney has highlighted the distinctiveness of the keratins along the entire nephron. The proximal nephron stains variably for vimentin, cytokeratin (CK) 8, CK18, and CK19 while the distal tubules immunostain for CK7, CK8, CK19, and CK18. CK8, CK18, and CK19 were expressed in large amounts throughout cortical and medullary collecting ducts, whereas vimentin, CK5/CK6, CK17, CK20, and HMWCK were restricted primarily to medullary collecting ducts. [7]

Amin et al.[2] documented CK8, CK18, CK19, and parvalbumin (100%), CD10 (85%), P504S/racemase (77%), kidney-specific cadherin (71.4%), CK7 (62%), Pax2 (42%), carbonic anhydrase IX, (36%), and CK34bE12 (15%) in TCRCC. Based on their immunohistochemistry and ultrastructural examination results, they concluded that TCRCC showed features of differentiation along both proximal convoluted tubules (Pax 2 immunoreactivity and short microvilli with brush border organization) and distal nephron (kidney-specific cadherin immunoreactivity and cytoplasmic interdigitation). [2] HMWCK was positive in 67% of collecting duct carcinoma, 33% of papillary RCCs, but was negative in all cases of tubulocystic carcinoma and renal medullary carcinoma again highlighting the uniqueness of TCRCC. [7]

Alpha-methyl CoA racemase (AMACR) is typically expressed in proximal nephron and not in the collecting ducts of kidney. [8] Among all RCCs, high expression of AMACR is found in papillary RCCs (type 1 and 2) and in spindle-cell carcinomas of the kidney while only a quarter clear cell RCCs stain for this antibody. [8] Chromophobe RCCs, urothelial carcinomas, and Bellini or collecting duct carcinomas show no immunoreactivity for AMACR. [8] Strong and diffuse AMACR was documented also in TCRCC similar to a PRCC. Tubulocystic carcinoma showed focal and/or weak CK7 immunostaining like low-grade papillary RCC unlike high-grade PRCC. [1]

Through comparative genomic microarray analysis, tubulocystic carcinoma showed gains of chromosome 17, but not chromosome 7, whereas most papillary RCCs showed chromosomal gains in both 7 and 17 (trisomies). [1] Therefore, Yang et al. concluded that TCRCC is closely related to papillary RCC as they often coexist in close proximity or intermingled each other, similar clustering of the two tumors in the gene profiling studies and show positive immunoreactivity of AMACR. [1] The Nonmedullary location and AAMCR positivity went against origin from collecting ducts. Also in two of their cases, they documented a transformation to high-grade papillary RCC though mechanism that was not clear. [1]

But Amin et al.[2] disagreed with these observations. They have stated that even after a comprehensive contemporary immunohistochemical panel for immunoprofiling of these tumors, they could not derive any conclusive evidence regarding any specific lineage of histogenesis for tubulocystic carcinoma and association with PRCC was not seen in any of the 31 cases studied. In our opinion, at least a small but definite subset of TCRCC are associated with PRCC and cases associated with PRCC do have a higher propensity for nodal metastases as seen in study by Yang et al.,[3] Zhou et al.,[6] and as also observed in the case we discuss.

While the debate about cell of origin is on, even more pressing is the unknown long-term behavior of this tumor raising some management issues. In our case, the para-aortic nodes show the presence of the metastatic tubulocystic carcinoma and Yang et al.[1] similarly observed lymph nodal metastasis in two of their cases at the time of the presentation (one from PRCC component and one from pure TCRCC). [3] Amin et al. in contrast did not find lymph nodal metastasis in their 31 cases of TCRCC, but disease progression (median follow-up of 56 months) occurred in 3 of the 31 patients: 1 with local recurrence, and 2 with distant metastasis to bone and liver. [2]

While radical nephrectomy would be the treatment in most patients with TCRCC, management of nodal metastases and recurrences is unclear and will be source of debate in the coming era with so many targeted therapies in RCC becoming available.

   Conclusion Top

Thus we have reported the youngest case of tubulocystic carcinoma with microscopic foci the papillary carcinoma of the kidney substantiating definite association between these two entities.

   Acknowledgement Top

Dr. Bijal Kulkarni, Kokilaben Dhirubhai Ambani Hospital for the referral material.

   References Top

1.Eble JN, Togashi K, Pisani P. Renal cell carcinoma In: Ebele JN, Sauter G, Epstein JI, Sesterhenn IA, editors. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press; 2004. p. 12-4.  Back to cited text no. 1
2.Amin MB, MacLennan GT, Gupta R, Grignon D, Paraf F, Vieillefond A, et al. Tubulocystic Carcinoma of the kidney: Clinicopathologic analysis of 31 cases of a distinctive rare subtype of Renal Cell Carcinoma. Am J Surg Pathol 2009;33:384-92.  Back to cited text no. 2
3.Yang XJ, Zhou M, Hes O, Shen S, Li R, Lopez J, et al. Tubulocystic carcinoma of the kidney: Clinicopathologic and molecular characterization. Am J Surg Pathol 2008;32:177-87.  Back to cited text no. 3
4.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 possible collecting duct origin. Urology 1997;50:679-84.  Back to cited text no. 4
5.Azoulay S, Vieillefond A, Paraf F, Pasquier D, Cussenot O, Callard P, et al. Tubulocystic carcinoma of the kidney: A new entity among renal tumors. Virchows Arch 2007;451:905-9.   Back to cited text no. 5
6.Zhou M, Yang XJ, Lopez JI, Shah RB, Hes O, Shen SS, et al. Renal tubulocystic carcinoma is closely related to papillary renal cell carcinoma: Implications for pathologic classification. Am J Surg Pathol 2009;33:1840-49.  Back to cited text no. 6
7.Skinnider BF, Folpe AL, Hennigar RA, Lim SD, Cohen C, Tamboli P, et al. Distribution of cytokeratins and vimentin in adult renal neoplasms and normal renal tissue: Potential utility of a cytokeratin antibody panel in the differential diagnosis of renal tumors. Am J Surg Pathol 2005;29:747-54.  Back to cited text no. 7
8.Molinié V, Balaton A, Rotman S, Mansouri D, De Pinieux I, Homsi T, et al. Alpha-methyl CoA racemase expression in renal cell carcinomas. Hum Pathol 2006;37:698-03.  Back to cited text no. 8

Correspondence Address:
Tanuja Shet
309/31, Prabhudarshan, SS Nagar, Amboli, Andheri, Mumbai - 400 058
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.77363

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