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  Table of Contents    
CASE REPORT  
Year : 2021  |  Volume : 64  |  Issue : 1  |  Page : 177-179
A rare case of a solitary fibrous tumor of vulva, displaying NAB2ex6-STAT6ex17 fusion


1 Department of Surgical Pathology, Tata Memorial Centre, HBNI; Division of Molecular Biology and Translational Medicine, Tata Memorial Centre, HBNI University, Parel, Mumbai, Maharashtra, India
2 Division of Molecular Biology and Translational Medicine, Tata Memorial Centre, HBNI University, Parel, Mumbai, Maharashtra, India
3 Department of Pathology, SMS Medical College, Jaipur, Rajasthan, India

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Date of Submission31-Jul-2019
Date of Decision30-Oct-2019
Date of Acceptance30-Oct-2019
Date of Web Publication8-Jan-2021
 

   Abstract 


A solitary fibrous tumor (SFT), although ubiquitous, is rarely documented in the female genital tract, especially confirmed by STAT6 immunostaining and underlying NAB2-STAT6 gene fusion. A 24-year-old female presented with a gradually increasing vulvar swelling in her right labia, which rapidly increased in size over 1-year duration. Radiologically, a subcutaneous, predominantly solid, lobulated mass, measuring 10 cm in the largest dimension was seen involving her right labia majora and perineum. She underwent tumor resection, elsewhere, where it was reported as a pleomorphic sarcoma. Histopathologic review revealed a cellular tumor comprising spindle cells, displaying mild nuclear variation, arranged diffusely and focally, in a hemangiopericytomatous growth pattern, within a collagenous stroma. Interspersed were blood vessels with perivascular hyalinization and few giant cells. By immunohistochemistry, tumor cells showed patchy immunostaining for CD34 and diffuse immunostaining for STAT6. Furthermore, the tumor displayed NAB2ex6-STAT6ex 17 fusion by RT-PCR technique. This case constitutes one of the few reported cases of vulvar SFT, confirmed by STAT6 immunostaining and the second such case, displaying NAB2-STAT6 gene fusion. Diagnostic and treatment implications are discussed herewith.

Keywords: NAB2-STAT6, solitary fibrous tumor vulva, STAT6, vulvar mesenchyal tumors

How to cite this article:
Rekhi B, Bapat P, Jindal A. A rare case of a solitary fibrous tumor of vulva, displaying NAB2ex6-STAT6ex17 fusion. Indian J Pathol Microbiol 2021;64:177-9

How to cite this URL:
Rekhi B, Bapat P, Jindal A. A rare case of a solitary fibrous tumor of vulva, displaying NAB2ex6-STAT6ex17 fusion. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Jan 28];64:177-9. Available from: https://www.ijpmonline.org/text.asp?2021/64/1/177/306526





   Introduction Top


A solitary fibrous tumor (SFT) is a ubiquitous tumor of fibroblastic lineage, invariably characterized by immunohistochemical (IHC) staining for CD34 and signal transducer and activator of transcription (STAT) 6, along with an underlying NAB2-STAT6 gene fusion, which appears to be its major pathogenic driver and constitutes its diagnostic molecular signature.[1],[2],[3] This genetic fusion arises from recurrent intrachromosomal rearrangements on 12q13 chromosome.[3]

Cases of SFT, confirmed by STAT6 immunostaining, have been rarely documented in the female genital tract.[4],[5],[6] Furthermore, only a single case of SFT, occurring in the vulva, confirmed with molecular testing for NAB2-STAT6 fusion, has been reported.[5]


   Case Report Top


A 24-year-old-female presented with a slow-growing vulvar swelling, which she noticed 3 years ago, of 2 to 3 cm size. Since a year ago, she felt a rapid growth of the lesion.

She underwent radiologic examination, followed by fine-needle aspiration cytology and surgical excision. Paraffin blocks of the excised tumor were submitted to us for review.

Radiologic findings

Magnetic resonance imaging (MRI) pelvis revealed a large, predominantly solid, lobulated mass measuring 6.5 cm × 9 cm × 10 cm, in the subcutaneous region of her right labia majora and perineum, sparing the muscles, containing multiple vascular voids [Figure 1]a.
Figure 1: (a) MRI pelvis displaying a large, lobulated, solid, mass involving the subcutis of vulva, sparing the muscles. (b) Microscopic findings: Predominantly, spindle cell neoplasm with rather banal appearing cells with perivascular and stromal hyalinization. Hematoxylin and Eosin (H and E, 200×). (c) Hemangiopericytomatous arrangement of tumor cells with interspersed pleomorphic cells (H and E, 200×). (d) Focal area displaying pleomorphic nuclei; however devoid of significant mitotic activity (H and E, 400×)

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Her FNAC was reported as a malignant tumor and subsequent excision was reported as a pleomorphic sarcoma, with free resection margins, closest being 1 mm away, at the referring laboratory.

Histopathologic findings

Gross examination (as per referring laboratory notes) revealed an oriented soft tissue mass, partly covered with skin and soft tissues, including muscles, measuring 12 cm × 6 cm × 5 cm. Cut surface revealed a grayish-white, multilobular circumscribed tumor, firm in consistency, measuring 11.5 cm × 5.5 cm × 4 cm.

Review of the nine paraffin blocks prepared from the excised specimen revealed a multinodular spindle cell neoplasm with cells exhibiting moderate to focally marked nuclear atypia (pleomorphic nuclei) and extensive perivascular and stromal hyalinization, including “star-burst”-like pattern. In addition, a distinct area of hemangiopericytomatous growth pattern of tumor cells was noted. Few mitotic figures were identified, fewer than 3 per 10/high power fields. There was no area of tumor necrosis [Figure 1]b, [Figure 1]c, [Figure 1]d.

By immunohistochemistry, tumor cells showed patchy positivity for CD34, diffuse intranuclear positivity for STAT6 (rabbit polyclonal antibody, directed against the C terminus of STAT6, sc-621; with dilution1:200, Santa Cruz Biotechnology, Santa Cruz, California, USA), diffuse positivity for MIC2 (cytoplasmic and incomplete membranous), and focal positivity for BCL2 and progesterone receptor (PR), while negativity for epithelial membrane antigen (EMA), pan cytokeratin, smooth muscle actin (SMA), desmin, and estrogen receptor (ER). Ki67 highlighted 3–4% tumor cell nuclei (low). INI1/SMARCB1 was diffusely retained [Figure 2]a, [Figure 2]b, [Figure 2]c.
Figures 2: (a-c) Immunohistochemistry. (a) Patchy CD34 positivity. Diaminobenzidine (DAB) 400×. (b) Diffuse STAT6 immunostaining (DAB, 200×). (c) Focal Ki-67/MIB1 (low). DAB, 400×. (d) RT-PCR for NAB2-STAT6 Fusions on 10% PAGE 1. 100 bp molecular weight marker, 2: Case positive for NAB2-STAT6 exon 6–exon 17 PCR (exon 6–exon 16 fusion type; 219 bp), 3, 4, 5, 6, 7, 8, and 9: Negative NAB2-STAT6 exon 6–exon 18 PCR, NAB2-STAT6 exon 3–exon 3, NAB2-STAT6 exon 4–exon 5, NAB2-STAT6 exon 5–exon 18, NAB2-STAT6 exon 7–exon 2 and NAB2-STAT6 exon 5–exon 3 and NAB2-STAT6 exon 2–exon 19. 10: Reagent control

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Diagnosis of a SFT with low-risk was offered.

Molecular analysis

Subsequently, formalin-fixed, paraffin-embedded tissue sections were tested for 8 fusion variants of NAB2-STAT6, using qualitative endpoint reverse-transcriptase (RT)-PCR technique, using specific primer sequences.[7] RNA extraction was performed using Recover All Total nucleic acid extraction kit. The tumor was found to be positive for NAB2ex6-STAT6ex17 gene fusion and negative for other variants [Figure 2]d.

The patient has been recommended a follow-up.


   Discussion Top


Cases of SFT have been rarely documented in the female genital tract, especially confirmed with STAT6 immunostaining, which presently constitutes the most specific diagnostic IHC marker for this tumor.[4],[5],[6] In a recently documented series of 25 cases of SFT involving the female genital tract, by Yang et al.,[4] 12 cases were reported in the vulva. Subsequently, Tardío et al.[5] reported two cases of primary vulvar SFT, including a classic and dedifferentiated subtype, both confirmed with STAT6 immunostaining and the second case, which further displayed NAB2-STAT6 gene fusion. The present case constitutes the second such case, confirmed with both, STAT6 immunostaining and molecular test for NAB2ex6-STAT6ex17 gene fusion.

Careful assessment of the histopathologic features, such as prominent stromal and perivascular hyalinization, and focal hemangiopericytomatous growth pattern of spindly cells, including large, multinucleate forms, reminiscent of a giant cell angiofibroma, along with lack of significant number of mitotic figures and tumor necrosis led to the consideration of an SFT, over a pleomorphic sarcoma, which was the diagnosis from two different referring laboratories, in the present case. Furthermore, positive IHC staining for CD34 and diffuse STAT6 immunostaining, with lack of desmin ruled out various differential diagnoses, such as mammary-type myofibroblastoma and angiomyofibroblastoma. Aggressive angiomyxoma constituted another differential diagnosis. It is relatively hypocellular tumor comprising stellate fibroblasts in a prominent myxoid stroma with interspersed blood vessels.

Some of the aforementioned tumor entities display CD34 immunostaining. However, none of these tumors is known to express diffuse STAT6 immunoexpression. Lack of EMA, AE1/AE3, and S100 protein immunostaining ruled out a myoepithelial tumor. Similarly, loss of EMA, (AE1/AE3) immunostaining, along with CD34 and STAT6 immunopositivity militated against a synovial sarcoma. This immunoprofile, coupled with diffusely retained INI1 also ruled out the possibility of a recently described myoepithelioma-like tumor in the vulva.[8] Desmin and SMA negativity made diagnosis of a smooth muscle tumor, less likely. In view of certain histopathologic features, such as mitotic figures less than 4/10 high power fields and lack of tumor necrosis and tumor size of 10 cm in the largest dimension, the present case was assigned low risk.[9] Unlike the earlier documented case of vulvar SFT, we observed focal immunostaining for PR in the present case.[5]

Subsequently, on molecular testing, the present case displayed NAB2-STAT6 fusion, which further confirmed the diagnosis of SFT. In contrast to the NAB2ex4-STAT6ex2 variant, which characterizes most classic thoracic SFTs and also reported in the single de-differentiated SFT, the present case displayed NAB2ex6-STAT6ex17 variant.[3],[5] Among various fusion variants, NAB2ex6-STAT6ex17 is more frequently observed in relatively younger patients and in extrathoracic sites, as the present case.[10] However, there is no significant prognostic implication of the variants of NAB2-STAT6 fusion.[7]

Considering a diagnosis of SFT with clear surgical resection margins, adjuvant radiation therapy, which was considered, in view of the initial diagnosis of a pleomorphic sarcoma, was obviated. Nonetheless, the patient has been recommended a follow-up.


   Conclusion Top


In conclusion, the present case constitutes one of the very few cases of vulvar SFT, confirmed with STAT6 immunostaining and molecular test. An index of suspicion is necessary for diagnosing a SFT, at unconventional sites. An exact diagnosis can be achieved with STAT6 immunostaining and NAB2-STAT6 gene fusion, especially in cases occurring at unconventional sites, such as the present case. A timely and an accurate diagnosis has significant therapeutic implications.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to b'e reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgements

We would like to thank Mrs. Manisha Chavan for immunohistochemical staining for STAT6.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Fletcher CDM, Bridge JA, Lee J-C. Extrapleural solitary fibrous tumour. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO Classification of Tumours of Soft Tissue and Bone. 2nd ed. Lyon: IARC; 2013. p. 80-2.  Back to cited text no. 1
    
2.
Doyle LA, Vivero M, Fletcher CDM, Mertens F, Hornick JH. Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol 2014;27:390-5.  Back to cited text no. 2
    
3.
Robinson DR, Wu Y-M, Kalyana-Sundaram S, Cao X, Lonigro RJ, Sung YS, et al. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet 2013;45:180-5.  Back to cited text no. 3
    
4.
Yang EJ, Howitt BE, Fletcher CDM, Nucci MR. Solitary fibrous tumour of the female genital tract: A clinicopathological analysis of 25 cases. Histopathology 2018;72:749-9.  Back to cited text no. 4
    
5.
Tardío JC, Machado I, Alemany I, López-Soto MV, Nieto MG, Llombart-Bosch A. Solitary fibrous tumor of the vulva: Report of 2 cases, including a de novo dedifferentiated solitary fibrous tumor diagnosed after molecular demonstration of NAB2-STAT6 gene fusion. Int J Gynecol Pathol 2018;37:547-53.  Back to cited text no. 5
    
6.
Rekhi B, Bapat P, Shetty O. A rare case of a vaginal solitary fibrous tumor, presenting as a cystic mass, showing NAB2ex4-STAT6ex2 fusion and STAT6 immunostaining. Int J Gynecol Pathol 2019;38:21-6.  Back to cited text no. 6
    
7.
Rekhi B, Shetty O, Tripathi P, Bapat P, Ramadwar M, Bajpai J, et al. Molecular Characterization of a Series of Solitary Fibrous Tumors, including Immunohistochemical expression of STAT6 and NATB2-STAT6 fusion transcripts, using reverse transcriptase (RT)-polymerase chain reaction (PCR) Technique: An Indian experience. Pathol Res Pract 2017;213:1404-11.  Back to cited text no. 7
    
8.
Kaku Y, Goto K, Kabashima K. Myoepithelioma-like tumor of the vulvar region presenting as a nonmyxoid spindle-cell neoplasm: A potential histologic mimicker of solitary fibrous tumor. Am J Dermatopathol 2016;38:e87-9.  Back to cited text no. 8
    
9.
Demicco EG, Wagner MJ, Maki RG, Gupta V, Iofin I, Lazar AJ, et al. Risk assessment in solitary fibrous tumors: Validation and refinement of a risk stratification model. Mod Pathol 2017;30:1433-42.  Back to cited text no. 9
    
10.
Huang SC, Li CF, Kao YC, Chuang IC, Tai HC, Tsai JW, et al. The clinicopathological significance of NAB2-STAT6 gene fusions in 52 cases of intrathoracicsolitary fibrous tumors. Cancer Med 2016;5:159-68.  Back to cited text no. 10
    

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Correspondence Address:
Bharat Rekhi
Department of Surgical Pathology, Room Number 818, 8th Floor, Annex Building, Tata Memorial Hospital, Dr. E.B. Road, Parel, Mumbai - 400 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_597_19

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