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Chromophobe renal cell carcinoma with massive sarcomatoid differentiation


 Dunarea de Jos University of Galati, Faculty of Medicine and Pharmacy, Galati, Romania

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Date of Submission25-Jan-2022
Date of Decision05-Feb-2022
Date of Acceptance05-Feb-2022
Date of Web Publication25-May-2022
 

   Abstract 


Chromophobe renal cell carcinoma (CRCC) is a distinct subtype of renal cell carcinoma with unique histological, immunohistochemical, cytogenetic, and ultrastructural features, which usually has a favorable clinical course, with only a small percentage of patients developing recurrence, metastasis, or death due to its complications. Sarcomatoid differentiation can occur in any subtype of renal cell carcinoma and currently represents the transformation into a higher degree of malignancy, its presence being associated with a reserved prognosis, with a reported incidence of average survival of less than 1 year after diagnosis. In this study, we present an unusual case of CRCC with massive sarcomatoid differentiation, which infiltrated the left adrenal gland and was surgically resected. The histological features of this tumor as well as a brief review of literature are presented.

Keywords: Immunochemistry, renal cell carcinoma, sarcomatoid differentiation


How to cite this URL:
Neagu AI, Neagu M, Stefanopol IA, Nechita A. Chromophobe renal cell carcinoma with massive sarcomatoid differentiation. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Jan 29]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=345898





   Introduction Top


Chromophobe renal cell carcinoma (CRCC) is a distinct subtype of renal cell carcinoma (RCC) with unique histological, immunohistochemical, cytogenetic, and ultrastructural features, which usually has a favorable clinical course, with only a small percentage of patients developing recurrence, metastasis, or death due to its complications. The first cases of CRCC were described in 1985 by Thoenes et al., and in the following years, the epidemiology and pathological features of this subtype of renal tumor were studied extensively.[1]

Sarcomatoid differentiation, formerly called sarcomatoid RCC, can occur in any subtype of RCC and currently represents the transformation into a higher degree of malignancy, its presence being associated with a reserved prognosis, with a reported incidence of average survival of less than one year after diagnosis.[2]

In this study, we present an unusual case of CRCC with massive sarcomatoid differentiation, which infiltrated the left adrenal gland and was surgically resected. The histological features of this tumor as well as a brief review of literature are presented.


   Case Report Top


A 47-year-old man with noncontributory medical history presented with hematuria, discomfort in the left abdominal quadrants, and weight loss. A thoraco-abdominal computed tomography revealed an inhomogeneous retroperitoneal mass situated on the topography of the left kidney, measuring 215 × 165 mm, infiltrating the left adrenal gland, and no other abnormalities consistent with metastases were found. The working diagnosis was left renal tumor and the patient underwent a left radical nephrectomy, with anterior transperitoneal approach.

According to the original pathology report, grossing showed that the resection specimen consisted of a fleshy, white tumoral mass with necrotic areas that measured 21 × 140 × 80 mm, and detached pyeloureteral junction, renal capsule, and left adrenal gland. After the initial optical microscopy examination, the diagnosis was pleomorphic rhabdomiosarcoma, and the patient was referred to our hospital for immunohistochemistry (IHC) study.

Our histological analysis in hematoxylin and eosin (H&E) stain revealed two distinct components of the tumor: a high-grade spindle cell sarcomatous extensive constituent and a minor epithelial component represented by small nests of tumor cells. There were areas of necrosis in the sarcomatoid part, accompanied by polymorphonuclear and lymphocytic inflammatory infiltrates.

The sarcomatoid component represented approximately 95% of the tumor and it was consisted of large solid areas of spindle cells with marked nuclear pleomorphism with relatively frequent giant multinucleated tumor cells and intense mitotic activity [approximately 18–20 mitoses per 10 high-power fields, total area of 1.96 mm2, [Figure 1]a, [Figure 2]. The minor carcinomatous component (5%) was represented by well-defined nests of medium-sized cells with eosinophilic cytoplasm, accentuated cell borders and irregular, angulated nuclei with coarse chromatin and prominent nucleoli [Figure 1]b. The renal capsule, the pyeloureteral junction, and the left adrenal gland were infiltrated by the tumor; thus, the pathologic stage of this tumor was pT4NxMx.
Figure 1: (a) The sarcomatoid component consists of highly pleomorphic spindle cells, H and E stain, magnification × 100; (b) The carcinomatous component consists of small nests of medium-sized cells with eosinophilic cytoplasm, accentuated cell borders, and angulated nuclei with prominent nucleoli, H and E stain, magnification × 200

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Figure 2: (a and b) Marked nuclear pleomorphism, with giant multinucleated tumor cells and bizarre mitotic figures, H and E stain, magnification × 400

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[Figure 3] shows the IHC profile of the tumor. Based on the morphology and IHC study, a diagnosis of CRCC with massive sarcomatoid transformation was made and the patient was further referred to the oncology department for adequate treatment.
Figure 3: Immunohistochemical aspects of the tumor. (a) The spindle cells are positive for CD10 and the chromophobe cells show negativity for this antibody, magnification × 200; (b) The sarcomatoid component shows diffuse, intense positivity for Vimentin, while the carcinomatous nests are negative, magnification × 100; (c) The carcinomatous nests show intense positivity for Cytokeratin 7, while the spindle cells are negative, magnification × 100; (d) A Ki-67 label index of 30% in the sarcomatous component, magnification × 400

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   Discussion Top


CRCC is the third most common histological subtype of RCC, representing less than 5% of RCC. Grossly, CRCC is an unencapsulated, well-circumscribed mass, with homogeneous solid appearance on sectioning and pale to dark brown color with hemorrhagic zones, areas of necrosis, cystic changes, or a central scar.[3]

Histologically, chromophobic cells are polygonal and tend to form sheets of epithelial cells with occasional glandular structures. Immunohistochemical markings suggest distal nephron-like cellular features, especially of the intercalated cell of the collecting ducts.[4]

Although many studies have shown, directly or indirectly, that CRCC has a less aggressive clinical behavior, even in the case of metastases, other researchers claim that there are no significant differences in terms of prognosis compared to other subtypes of RCC.[5] Studies in the literature have reported a 10-year survival rate between 80% and 90%.[2],[5] Also, death occurs in only about 5%–6% of patients with CRCC.[6]

One of the largest studies, which included 145 cases, found that the pT stage of the tumor, tumor necrosis, and sarcomatoid transformation were predictors of the aggressive behavior of these tumors.[1]

Sarcomatoid features in any subtype of RCC are considered predictors of aggressive clinical behavior. Some studies have argued that of all RCCs, the chromophobic subtype is proportionally the most common subtype with sarcomatoid features.[3],[6]

Numerous researchers have attempted to develop a grading system for CRCC, given the inherent geographic nuclear crowding and the presence of anaplasia. Lohse et al.[7] applied a four-tiered standardized grading system and showed a significant overlap between classes 3, 2, and 1 of CRCC. Ohashi et al.[6] proposed a two-tiered grading system (low grade vs. high grade) that used as a parameter for the existence of sarcomatoid differentiation and tumor necrosis.

Heterologous sarcomatoid components, such as chondrosarcomatous, osteosarcomatous, or rhabdomyosarcomatous components, have also been reported.[8] Brunelli et al.[9] demonstrated that the appearance of both epithelial and sarcomatoid elements of CRCC is caused by genetic abnormalities, sarcomatoid differentiation being determined by changes in chromosomes 1, 2, 6, 10, and 17. The disease-specific survival rate was found to be 22% and 13% after 5 and 10 years, respectively, and the sarcomatoid component in a percentage greater than or equal to 50% and lymphovascular invasion were associated with decreased survival.[8]

Immunohistochemically, Cytokeratin 7 (CK7) is a very important marker, showing a diffuse expression in over 75% of cases; CRCC tumors also are diffusely positive for CD117 (c-Kit).[8] PDL1 expression in ≥5% of tumor cells is rare in CRCC and is seen in approximately 5.6% of patients.[10]

Most often, the differential diagnosis of CRCC is made with renal oncocytoma, which has histological similarities, especially with the eosinophilic variant, where IHC can help to solve the diagnostic dilemma. CK7 is intensely positive diffuse in CRCC and is usually negative in renal oncocytoma. Loss of RB1 expression by IHC is common in CRCC and is not seen with oncocytoma.[8],[9],[10] To diagnose CRCC with sarcomatoid differentiation, it is recommended to perform an immunohistochemical study, which will highlight the positivity of markers for epithelial cells in the tumor, such as EMA and cytokeratins.[9],[10]


   Conclusions Top


Our case represents a CRCC with massive sarcomatoid differentiation with invasion of the renal capsule and the left adrenal gland and with no metastases. This subtype of tumor is not frequent and in contrast with the classical form of chromophobe cell carcinoma, the diagnosis carries a worse prognosis. To diagnose this tumor, it is recommended to perform an immunohistochemical study. Finally, larger studies are needed to elucidate the clinical behavior of sarcomatoid CRCC.

Acknowledgements

The authors are grateful to Dunarea de Jos University for the library facility support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Thoenes W, Storkel S, Rumpelt HJ. Human chromophobe cell renal carcinoma. Virchows Arch B Cell Pathol Incl Mol Pathol 1985;48:207-17.  Back to cited text no. 1
    
2.
Leibovich BC, Lohse CM, Cheville JC, Zaid HB, Boorjian SA, Frank I, et al. Predicting oncologic outcomes in renal cell carcinoma after surgery. Eur Urol 2018;73:772-80.  Back to cited text no. 2
    
3.
Cheville JC, Lohse CM, Zincke H, Weaver AL, Blute ML. Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol 2003;27:612-24.  Back to cited text no. 3
    
4.
Motzer RJ, Bacik J, Mariani T, Russo P, Mazumdar M, Reuter V. Treatment outcome and survival associated with metastatic renal cell carcinoma of nonclear-cell histology. J Clin Oncol 2002;20:2376-81.  Back to cited text no. 4
    
5.
Paner GP, Amin MB, Alvarado-Cabrero I, Young AN, Stricker HJ, Moch H, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: Prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol 2010;34:1233-40.  Back to cited text no. 5
    
6.
Ohashi R, Martignoni G, Hartmann A, Calio A, Segala D, Stohr P, et al. Multi-institutional reevaluation of prognostic factors in chromophobe renal cell carcinoma: Proposal of a novel two-tiered grading scheme. Virchows Arch 2020;476:409-18.  Back to cited text no. 6
    
7.
Lohse CM, Blute ML, Zincke H, Weaver AL, Cheville JC. Comparison of standardized and nonstandardized nuclear grade of renal cell carcinoma to predict outcome among 2,042 patients. Am J Clin Pathol 2002;118:877-86.  Back to cited text no. 7
    
8.
Quiroga-Garza G, Khurana H, Shen S, Ayala AG, Ro JY. Sarcomatoid chromophobe renal cell carcinoma with heterologous sarcomatoid elements. A case report and review of the literature. Arch Pathol Lab Med 2009;133:1857-60.  Back to cited text no. 8
    
9.
Brunelli M, Gobbo S, Cossu-Rocca P, Cheng L, Hes O, Delahunt B, et al. Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma. Mod Pathol 2007;20:303-9.  Back to cited text no. 9
    
10.
Choueiri TK, Fay AP, Gray KP, Callea M, Ho TH, Albiges L, et al. PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol 2014;25:2178-84.  Back to cited text no. 10
    

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Correspondence Address:
Marius Neagu,
Dunarea de Jos University of Galati, Faculty of Medicine and Pharmacy, 35 Cuza st., Galati
Romania
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_85_22



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