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Year : 2015  |  Volume : 58  |  Issue : 3  |  Page : 354-355
Clear cell renal cell carcinoma with hemangioblastoma-like features: A recently described pattern with unusual immunohistochemical profile

1 Department of Pathology, Tata Medical Center, Kolkata, West Bengal, India
2 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Urological Surgery, Tata Medical Center, Kolkata, West Bengal, India

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Date of Web Publication14-Aug-2015


The diagnosis of clear cell renal cell carcinoma may sometimes pose challenges because of the presence of uncharacteristic morphology, varied immunophenotypic patterns and due to lack of molecular or genetic determinants. More often, the morphological variations can be easily overlooked in routine practice and a more common diagnosis is usually put forward. Solid, acinar and alveolar are the common patterns described in the literature. We report a recently described pattern of clear cell renal cell carcinoma which has hemangioblastoma-like morphology and an unusual immunoprofile. In our case, the tumor showed a diffuse hemangioblastoma-like pattern and diffuse positivity for Alpha-inhibin on immunohistochemistry. A thorough literature search, extensive sampling and an expanded immunohistochemistry panel revealed a clear cell renal cell carcinoma component. Presence of renal vein thrombosis and focal necrosis were other helpful features in discerning the malignant nature of tumor.

Keywords: Clear cell renal cell carcinoma, hemangioblastoma, Alpha-inhibin

How to cite this article:
Sancheti S, Menon S, Mukherjee S, Arun I. Clear cell renal cell carcinoma with hemangioblastoma-like features: A recently described pattern with unusual immunohistochemical profile. Indian J Pathol Microbiol 2015;58:354-5

How to cite this URL:
Sancheti S, Menon S, Mukherjee S, Arun I. Clear cell renal cell carcinoma with hemangioblastoma-like features: A recently described pattern with unusual immunohistochemical profile. Indian J Pathol Microbiol [serial online] 2015 [cited 2020 Jun 6];58:354-5. Available from: http://www.ijpmonline.org/text.asp?2015/58/3/354/162898

   Introduction Top

Hemangioblastoma is a benign neoplasm that usually occurs in the central nervous system. [1],[2] However, there are rare case reports of hemangioblastomas arising in the kidney. Recently, two cases of clear cell renal cell carcinoma (ccRCC) with hemangioblastoma like features have been described by Montironi et al. [3] Due to the presence of morphologic and immunohistochemical overlap with renal hemangioblastoma, diagnosis may be challenging unless there is an unequivocal ccRCC component. Our case showed a predominant hemangioblastoma-like pattern and the focal ccRCC-like component which was discovered in retrospect with extensive sampling and immunohistochemical studies. Venous extension of tumor thrombus and necrosis was also seen. Whether this represents a distinct pattern of ccRCC or should be categorized separately is yet to be determined, however, awareness of this pattern is important to distinguish it from hemangioblastoma which is a benign tumor. We present a case which, though malignant, mimicked a benign hemangioblastoma.

   Case Report Top

A 69-year-old male, on follow-up for carcinoma of the bladder, presented with recent hematuria and passage of clots in urine. Computed tomography scan revealed a left renal mass (6.5 cm × 5.5 cm) at mid portion of the kidney with contrast enhancement. Magnetic resonance imaging was suggestive of a vascular lesion of the kidney. The patient underwent a left total nephrectomy. The cut surface revealed a well-circumscribed tumor measuring 4.0 cm × 4.0 cm × 3.0 cm at the mid portion of kidney. Serial sections through the tumor showed a variegated yellow hemorrhagic cut surface without extension to the perirenal fat. Tumor was seen infiltrating into the hilar fat and a tumor thrombus was seen extending into the renal vein. Representative sections were submitted for examination. Microscopy showed a tumor composed of sheets of oval to polygonal cells and a prominent vascular network. The tumor cells varied in size with pale to eosinophilic cytoplasm with fine vacuoles and hyaline globules in many cells. Individual cells showed moderate nuclear atypia with inconspicuous nucleoli (as shown in [Figure 1]). Mitotic figures were not seen. An initial immunohistochemistry panel was done which showed tumor cells to be diffusely positive for Alpha-inhibin and negative for CD10, RCC, and epithelial membrane antigen (EMA). Sections from the tumor thrombus also revealed a similar immunoprofile. Additional sections from the tumor were taken due to suspicion of a ccRCC component. The tumor showed similar morphology along with focal areas of necrosis and hemosiderin pigment deposits. Immunohistochemistry repeated on additional sections showed most of the tumor to be diffusely and strongly positive for Alpha-inhibin, but a few tumor islands were negative for this marker. These tumor islands were positive for cytokeratin (AE1/AE3), EMA and CD10 (as shown in [Figure 2]). These tumor nests could represent a coexistent ccRCC component. Tumor cells were negative for RCC marker, S-100p, PAX-8, HMB-45, and Melan-A. CD-31 highlighted the vascular endothelial lining but was negative in tumor cells. The picture was similar to that described by Montironi et al., but a gradual transition between the hemangioblastoma-like component and the areas of ccRCC was not seen in our case. [3] A diagnosis of ccRCC with hemangioblastoma-like features with distinct immunoprofile was made.
Figure 1: (a) Tumor composed of sheets of oval to polygonal cells and a prominent vascular network (H and E ×200). (b) Tumor cells strongly positive for Alpha-inhibin immunostain

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Figure 2: Immunohistochemistry shows tumor cells to be focally positive for (a) cytokeratin, (b) epithelial membrane antigen, (c) CD-10 and negative for (d) Melan-A, (e) HMB-45, and (f) CD31 (highlights blood vessels)

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   Discussion Top

Renal cell carcinomas with unusual and overlapping morphological and immunophenotypic features have been rarely reported in literature. Renal hemangioblastomas are very rare with only 11 cases published in the English literature. [3],[4],[5] The predominant hemangioblastoma-like pattern seen in our case showed rich capillary network surrounded by cells with clear foamy cytoplasm similar to stromal cells of renal hemangioblastoma as described recently by Zhao et al. and by others. [3],[4],[5],[6],[7] Tumor also showed diffuse Alpha-inhibin positivity which added to the diagnostic difficulty. There are rare case reports of ccRCC with Alpha-inhibin positivity in the literature. [8] However, those cases also showed positivity for CD10 which helped in the diagnosis of ccRCC. In our case, the tumour was predominantly negative for CD10 with a small focus showing typical immunohistochemical features of ccRCC, positive for CD10 and EMA. These areas did not show any significant morphological difference from the other parts of the tumor and only immunohistochemistry made it possible to highlight them. Montironi et al. have raised a question whether renal hemangioblastomas reported in the literature should be considered as true renal hemangioblastomas or a diffuse hemangioblastoma-like change in a ccRCC. [3] In addition our case had venous tumor thrombus and necrosis which also helped in discerning the malignant nature of the tumor as these features have never been described in a hemangioblastoma, which is a benign tumor. [4] Pax-8 and S-100 have been described as variable in various studies and are not helpful in separating the two differentials. [5],[9]

   Conclusion Top

Renal cell carcinoma can be obscured by a predominant hemangioblastoma like pattern. In cases, which lack definite features of malignancy, it is important to be aware of this immunohistological pattern of ccRCC to avoid making an erroneous conclusion of a benign condition. Larger studies with molecular and immunological testing are required to determine the clinical significance and prognosis of this entity as there are only two reported cases in the published English literature previously, this being the third one.

   References Top

Hussein MR. Central nervous system capillary haemangioblastoma: The pathologist's viewpoint. Int J Exp Pathol 2007;88:311-24.  Back to cited text no. 1
Aldape KD, Plate KH, Vortmeyer AO, Zagzag D, Neumann HP. Haemangioblastoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO Classification of Tumours of the Central Nervous System. Lyon, France: IARC Press; 2007. p. 184-6.  Back to cited text no. 2
Montironi R, Lopez-Beltran A, Cheng L, Galosi AB, Montorsi F, Scarpelli M. Clear cell renal cell carcinoma (ccRCC) with hemangioblastoma-like features: A previously unreported pattern of ccRCC with possible clinical significance. Eur Urol 2014;66:806-10.  Back to cited text no. 3
Plate KH, Vortmeyer AO, Zagzag D, Neumann HP. Von Hippel-Lindau disease and haemangioblastoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO Classification of Tumours of the Central Nervous System. Lyon, France: IARC Press; 2007. p. 215-7.  Back to cited text no. 4
Zhao M, Williamson SR, Yu J, Xia W, Li C, Zheng J, et al. PAX8 expression in sporadic hemangioblastoma of the kidney supports a primary renal cell lineage: Implications for differential diagnosis. Hum Pathol 2013;44:2247-55.  Back to cited text no. 5
Nonaka D, Rodriguez J, Rosai J. Extraneural hemangioblastoma: A report of 5 cases. Am J Surg Pathol 2007;31:1545-51.  Back to cited text no. 6
Ip YT, Yuan JQ, Cheung H, Chan JK. Sporadic hemangioblastoma of the kidney: An underrecognized pseudomalignant tumor? Am J Surg Pathol 2010;34:1695-700.  Back to cited text no. 7
Jung SM, Kuo TT. Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma. Mod Pathol 2005;18:788-94.  Back to cited text no. 8
Weinbreck N, Marie B, Bressenot A, Montagne K, Joud A, Baumann C, et al. Immunohistochemical markers to distinguish between hemangioblastoma and metastatic clear-cell renal cell carcinoma in the brain: Utility of aquaporin1 combined with cytokeratin AE1/AE3 immunostaining. Am J Surg Pathol 2008;32:1051-9.  Back to cited text no. 9

Correspondence Address:
Dr. Indu Arun
Department of Pathology, Tata Medical Center, 14, Main Arterial Road (E-W), Newtown, Rajarhat, Kolkata - 700 156, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.162898

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