COW-2021-18

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1. Solitiary fibrous tumor with round cell morphology
2. NAB2-STAT6

Upon histologic examination, the sections showed an unencapsulated, but fairly circumscribed uniformly cellular tumor. The tumor cells were arranged in whorls, sheets, and short fascicles. Perivascular arrangement was also identified at many foci. The tumor cells were round to oval and focally spindled. There was mild to moderate nuclear atypia, finely dispersed nuclear chromatin, small nucleoli, and scant to moderate clear to eosinophilic cytoplasm. No necrosis was identified. The mitotic activity was moderately high (up to 5 per 10 high-power fields). Foci with large, staghorn-type vessels were seen. The neoplastic cells exhibited a STAT6+/BCOR+/CD34-/BCL2 (focal+)/CD99+/CD31-/PAX8-/CD10-/NKX2.2-/FLI1-/SATB2-/Desmin-/Smooth muscle actin (focal+)/S100-/CD117-/pancytokeratin-/TLE1-/CD45- immunophenotype. The Ki-67 proliferation index was 20%. Fluorescent in situ hybridization test revealed a STAT6 break-apart positivity, while break-apart FISH assay for BCOR was negative. As BCOR immunohistochemistry was diffusely positive in the neoplastic cells, a multiplexed sequencing assay was performed on an Illumina® HiSeq 4000 platform which failed to demonstrate any mutation (rearrangement) other than NAB2 and STAT6 genes.

A diagnosis of solitary fibrous tumor (SFT) with round cell morphology (low risk class; score = 3) was rendered. SFT is a fibroblastic tumor with thin-walled vasculature and NAB2-STAT6 gene rearrangement. This can occur at any anatomic site including soft tissue and visceral locations. SFTs usually have a so called ‘patternless’ arrangement with haphazardly arranged spindle cells and varying amounts of collagen and small- to medium-sized and thin-walled blood vessels with staghorn appearance. Traditionally, SFTs express CD34, CD99, BCL2, epithelial membrane antigen, and STAT6; the latter has emerged as a sensitive and specific marker which identifies the NAB2-STAT6 gene fusion product (1). While CD34+/CD99+ positivity is characteristic for SFT and aid in differentiating this tumor from other mesenchymal tumors, there is a subset of SFTs, in which the expression of these two markers may be decreased or absent. These tumors are considered dedifferentiated and show necrosis, cystic degeneration, more frequent mitosis, and tend to lose the typical staining pattern of conventional SFT; CD34 being lost in 50% cases (2-6). In such diagnostically challenging scenarios, a STAT6 immunostaining is extremely helpful. Also, STAT6 immunoexpression is more sensitive than STAT6-NAB2 FISH assay, making STAT6 IHC a valuable tool to arrive at a correct diagnosis (7-8).

Renal SFTs are relatively rare neoplasms with only 55 cases reported till date. Most of the neoplasms exhibited typical spindle cell histology with a CD34 positive phenotype. Round cell SFTs are rare (9, 10). Tumors with round cell morphology especially on the needle core biopsy and at a visceral location are of diagnostic challenge as SFT is not often considered in the differential diagnosis of a round cell tumor. Other round cell tumors that are considered in the differentials, particularly in the kidney, include Ewing’s family of tumor, Wilms’ tumor, Desmoplastic small round cell tumor, Synovial sarcoma, BCOR-CCNB3-associated round cell sarcoma, undifferentiated round cell sarcoma with CIC-DUX4 fusion, and embryonal rhabdomyosarcoma (11).

In conclusion, SFTs with predominantly round cell morphology are extremely rare renal neoplasms and they tend to lose CD34 similar to other visceral and soft tissue round cell SFTs, highlighting the diagnostic utility of adding STAT6 to the IHC panel when trying to classify round cell tumors of the kidney.

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2. Mosquera JM, Feltcher C DM. Expanding the spectrum of malignant progression in solitary fibrous tumors: a study of 8 cases with a discrete anaplastic component- is this dedifferentiated SFT? Am J Surg Pathol. 2009;33(9):1314-21.

3. Demicco EG, Wagner MJ, Maki RG, Gupta V, Iofin I, Lazar AJ, Wang WL. Risk assessment in solitary fibrous tumors: validation and refinement of a risk stratification model. Mod Pathol. 2017 Oct;30(10):1433-1442.

4. Guillou LFJ, Fletcher CDM, Mandahi N. In: World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Soft Tissue and Bone. Fletcher CDM, Unni KK, Mertens F, editor. Lyon: IARCPress; 2002. Extrapleural solitary fibrous tumour and hemangiopericytoma; pp. 86–90.

5. Fine SW, McCarthy DM, Chan TY, Epstein JI, Argani P. Malignant solitary fibrous tumor of the kidney: report of a case and comprehensive review of the literature. Arch Pathol Lab Med. 2006;130:857–61.

6. Yokoi T, Tsuzuki T, Yatabe Y, Suzuki M, Kurumaya H, Koshikawa T, Kuhara H, Kuroda M, Nakamura N, Nakatani Y. et al.Solitary fibrous tumour: significance of p53 and CD34 immunoreactivity in its malignant transformation. Histopathology. 1998;32: 423.32.

7. Yoshida A, Tsuta k, Ohno M, Yoshida M, Narita y, Kawai A, et al. STAT6 Immunohistochemistry Is Helpful in the Diagnosis of Solitary Fibrous Tumors. Am J Surg Pathol. 2014;38(4):552–559.

8. Koelsche C, Schweizer L, Renner M, Warth A, Jones DTW, Sahm F, et al. Nuclear relocation of STAT6 reliably predicts NAB2–STAT6 fusion for the diagnosis of solitary fibrous tumour. Histopathology. 2014;65(5):613–622.

9. Kouba E, Simper NB, Chen S, Williamson SR, Grignon DJ, Eble JN, MacLennan GT, Montironi R, Lopez-Beltran A, Osunkoya AO, Zhang S, Wang M, Wang L, Tran T, Emerson RE, Baldrige LA, Monn MF, Linos K, Cheng L. Solitary fibrous tumour of the genitourinary tract: a clinicopathological study of 11 cases and their association with the NAB2-STAT6 fusion gene. J Clin Pathol. 2017 Jun;70(6):508-514.

10. Tan SY, Szymanski LJ, Galliani C, Parham D, Zambrano E. Solitary Fibrous Tumors in Pediatric Patients: A Rare and Potentially Overdiagnosed Neoplasm, Confirmed by STAT6 Immunohistochemistry. Pediatr Dev Pathol. 2018 Jul-Aug;21(4):389-400.

11. Argani P, Kao YC, Zhang L, Sung YS, Alaggio R, Swanson D, Matoso A, Dickson BC, Antonescu CR. BCOR Overexpression in Renal Malignant Solitary Fibrous Tumors: A Close Mimic of Clear Cell Sarcoma of Kidney. Am J Surg Pathol. 2019 Jun;43(6):773-782.

Anandi Lobo
Sambit K. Mohanty
CORE Diagnostics and Advanced Medical Research Institute
India
sambit.mohanty@corediagnostics.in

Kidney

Solitary fibrous tumor; round cell tumor; CD34 loss; STAT6; kidney