The solitary fibrous tumor is one of the rare mesenchymal origin tumors with an incidence of <0.1/100,000 people. 12 This tumor tends to pose diagnostic challenges due to similarity in clinical, radiological and histological features with several more common soft tissue tumors like synovial sarcoma, leiomyosarcoma, phyllodes, malignant peripheral nerve sheath tumor (MPNST), etc. The tumor was previously reported to primarily occur in pleura which is still the most common site accounting for 70% of the cases. However, now it is known to occur at any anatomical sites with a varying spectrum of histological features. Histologically, it ranges from hypocellular to hypercellular tumors to anaplastic SFT with sarcomatous transformation. 3 Fibroblastic cell is considered as the cell of origin in these tumors.

Historically, SFTs are sub-classified into three groups: i) Benign (local disease); ii) not otherwise specified (usually not metastatic); and iii) malignant. 4 The general criteria adopted for malignant SFTs include a large tumor size, mitotic rate of ≥4/10 highpower fields (HPFs), nuclear pleomorphism, and necrosis. Demicco et al. proposed a modified fourvariable risk stratification model for development of metastasis in solitary fibrous tumors based on age, tumor size, necrosis and mitotic count into three risk classes of low, intermediate, and high risk. 5 The diagnosis as well as risk stratification of SFT at unusual sites like the breast are very demanding and not possible on clinical and radiological examination. Accurate diagnosis requires a combined evaluation of clinical, pathological, immunohistochemical and molecular features together. Herein, we report a case of malignant SFT in a 52 year-old lady with a focus on diagnosis.

A 52-year-old lady presented with a progressively enlarging lump in the left breast over the last 12 Figure 1A, 1B). A biopsy was also done outside which confirmed the lesion as a phyllodes tumor. At our center, a biopsy was repeated by the surgeon to confirm the diagnosis. For metastatic work-up, given the rapidly enlarging large mass, a positron emission tomography (PET) scan was also done. The PET scan showed a FDG avid soft tissue density mass measuring 8.4 (Anteroposterior) x 7.6 (mediolateral) x 8.8 (craniocaudal) cm involving the entire quadrant with hypo metabolite areas suggestive of necrosis ( Figure 1C). No significant family history was present.

The core needle biopsy showed a cellular tumor comprising spindle to oval cells arranged in long fascicles, and a focally herringbone pattern with intervening capillary channels in a characteristic hemangiopericytomatous pattern. The tumor cells showed moderate nuclear pleomorphism, frequent mitotic activity including atypical forms (5/10 hpf), and an infiltrative growth pattern. Perivascular accentuation by tumor cells and the area of hyalinization were also seen. A focal area of necrosis was noted. No glandular/ductal component was seen. The possibility of a primary mesenchymal tumor with the following differentials was considered: Solitary fibrous tumor (SFT), synovial sarcoma, malignant phyllodes, leiomyosarcoma, metaplastic carcinoma and malignant peripheral nerve sheet tumor (MPNST). An immunohistochemistry (IHC) panel comprising CK, ER, PR, CD34, SMA, STAT6, Caldesmon, SOX10, TLE-1, and MIB-1 was applied to confirm the diagnosis. The tumor cells showed diffuse nuclear positivity for STAT6 with CD34 highlighting blood vessels and were negative for CK, ER, PR, Caldesmon, SMA, SOX10, and TLE-1. The MIB-1 labeling index was approximately 20%. Based on the histomorphology and IHC findings a diagnosis of SFT, the intermediate risk group was suggested with advice for NAB2-STAT6 fusion gene study. Following the histopathology report, surgeons performed a modified radical mastectomy. On gross examination, a large grey-white fibrous lobulated unencapsulated tumor measuring 8 x 7.5 x 6 cm involving entire quadrants with area of necrosis was seen. A total 16 lymph nodes were retrieved from the attached axillary tail. The tumor showed similar histological features as in the core biopsy. The lymph nodes showed reactive changes, free of tumor.

The patient was asymptomatic until the last follow-up four months after the surgery.

SFTs were formerly known with different terminologies like pleural fibroma, hemangiopericytoma, benign mesothelioma, localized fibrous tumor, giant cell angiofibroma and subserosal fibroma. The peculiar finding in SFT is characteristic staghorn-like blood vessels and perivascular accentuation of the tumor cells. These characteristics are very helpful in making a correct diagnosis of SFT, particularly at unusual sites. Malignant SFTs are usually large, hypercellular tumors displaying at least focal moderate to marked cytological atypia, tumour necrosis, numerous mitoses (≥ 4 mitoses/10 high-power fields), and/or infiltrative margins. 6 In the present case, all the features supportive of malignant SFT described by Vimi et al. were present to label it as malignant SFT. 6 In mammography, it was categorized as BI-RADS 4B which is suspicious for malignancy (10-49%). PET scan was suggestive of a malignant lesion.

The modified Demicco Score, which is based on mitotic activity, patient age, tumor size and tumor necrosis to predict the risk of metastasis, is the most commonly used system for the risk stratification of SFTs. Based on this, SFTs can be categorized into three groups: Low, intermediate and high-risk SFTs. However, it is mainly applicable to soft-tissue and pleural SFTs, and valuable in planning the treatment strategy for high-risk SFTs, but its utility for other rare site SFTs as in the breast is not validated. Moreover, it is not an advocated prediction model for the local recurrence in SFTs. The index case, as per the modified Demicco Score fulfilled the intermediate risk category group.

In the present case, the IHC played a critical role in the diagnosis. The minimal panel which helped us comprised CK, ER, PR, CD34, SMA, STAT6, Caldesmon, SOX10, TLE-1, and MIB-1. STAT6 is the most helpful sensitive and specific marker for SFTs. 7 It is even more useful in malignant SFT cases, where the conventional CD34 may be negative. In the current case, CD34 was negative; however, STAT6 showed diffuse nuclear positivity.

We have also evaluated CD44 IHC expression in the present case. CD44 is a cell adhesion molecule that also represents a biomarker of cancer stem cells, and plays an important role in epithelialmesenchymal transition. Demirag et al. evaluated the expression of CD44 and matrix metalloproteinases (MMP-2) in pleuro-pulmonary SFTs. 8 They reported MMP-2 positivity in two malignant SFT cases; however, CD44 expression was observed in benign cases only. In contrast, we found diffuse positivity of CD44 in the present case. The role of CD44 in SFTs pathogenesis and malignant potential needs to be further validated.

To the best of our knowledge, only six cases of malignant SFTs in the breast are reported in the literature. The recurrence rate of malignant SFT is high, and a complete removal is suggested for better outcomes. 9 However, metastasis is rarely documented in any case. In the present case, axillary lymph nodes were free of tumour. PET CT was also not suggestive of any distant metastasis. As a richly vascular tumor treatment options may have angiogenic pathway blockers but due to a limited number of cases, they are still on trial. 10

Due to the infrequency of breast SFT, it diagnosis is a matter of exclusion. Clinical and radiological features are not specific to make a certain diagnosis and the usual differentials considered are phyllodes tumor or carcinoma. A careful histological examination and IHC interpretation are very important to make an accurate diagnosis.

Informed consent from the patient was obtained.