Fumarate hydratase (FH) deficient uterine leiomyomas account for only 0.4 % of all uterine leiomyomas. They are characterized by some distinct histological features and may be associated with Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Herein we present a series of five cases of FH deficient uterine leiomyomas in patients with a mean age of 30 years. All five patients underwent myomectomy. Three of these cases had an outside histopathologic diagnosis ranging from Smooth muscle tumor of uncertain malignant potential (STUMP) to Leiomyosarcoma while two cases were operated at our centre. All five cases were reported as suggestive of FH deficient leiomyomas and were advised germline testing along with genetic counselling. Immunohistochemically four of the cases showed moderate to strong positivity for 2-SC with a complete loss or reduced expression of FH while one case showed absence of 2-SC staining. Mutations in FH lead to reduced enzyme activity and accumulation of fumarate leading to a complete loss or aberrant reduced expression seen on immunohistochemistry, which confirms the diagnosis. It is important to differentiate it from a leiomyosarcoma or other malignant spindle cell tumors as these tumors follow a benign course. Their association with HLRCC also needs to be established for a suitable follow up since HLRCC-associated RCCs are often aggressive. Management of such leiomyomas is myomectomy or hysterectomy with advice of genetic testing to rule out HLRCC. Histomorphology and immunohistochemistry are imperative for a correct and timely diagnosis.

Background: Aberrant T cell antigen expression has been well documented in diffuse large B cell lymphomas. However, co-expression of multiple T cell antigens including CD3, which has been considered a specific marker for T cells is extremely rare. Awareness about such aberrant expression is important so as not to misdiagnose or wrongly classify a lymphoma. The aim of this article is to report such a case. Case presentation: A 68-year-old postmenopausal lady, diabetic and hypertensive, presented with an axillary lump of one week’s duration. There was no other relevant medical history. Ultrasonography revealed multiple hypoechoic cystic lesions varying in size from 3.9 to 4.2 cm³. Aspiration was suggestive of an infective pathology. Excision biopsy of the mass was diagnosed as diffuse large B cell lymphoma with aberrant T cell antigen expression. She received 4 cycles of chemotherapy after which she was lost to follow-up. Conclusion: The case presented as a diagnostic dilemma for the pathologist. The predicament lies in classifying it as a B cell lymphoma with an aberrant expression of T cell markers versus a T cell lymphoma with an aberrant B cell marker expression which has a significant implication on the treatment offered. This can be solved by looking at the expression of the B cell specific transcription factors. The key to diagnosis lies in the knowledge of their existence and the application of a panel of markers.

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis. SETTLE is a biphasic lobulated tumor composed of spindle shaped cells along with glandular formations seen on histopathological examination. Despite its typical morphology it is commonly misdiagnosed on histopathology due to its rarity and overlapping morphology with other close mimics such as a carcinoma, synovial sarcoma and thymoma. Herein we report such a case occurring in a middle aged female presenting with a neck mass. She had an initial diagnosis of metastatic poorly differentiated squamous cell carcinoma possibly with an orophayngeal primary in view of co expression of CK, p40 and p16 on immunohistochemistry. The patient underwent surgical resection with modified neck dissection. On review at our hospital it was diagnosed as SETTLE and she remains disease free after a follow-up period of 1 year. Diligent histopathological examination espoused with a judicious panel of IHC markers in conjunction with clinicoradiological findings forms the mainstay of diagnosis. Diffuse and strong p16 immunoexpression has not been documented or evaluated in literature so far, and needs to be explored for its diagnostic utility in this rare entity.

SMARCB1 (INI-1) deficient vulvar neoplasms are rare tumors with scarce available literature. These tumors can be comprised of proximal type epithelioid sar

Vulval leiomyosarcomas with variant features are rare with limited data available in the literature compared to their uterine counterparts. Gynecologic leiomyosarcoma with nuclear receptor 4A3 (NR4A3) gene fusion is a rare, recently described neoplasm that has been reported mostly in the uterus and rarely in the pelvis. Herein, we report the first case of this entity occurring as a primary vulva tumor in a 46-year-old patient. Histologic examination showed a multi-nodular tumor composed of monomorphic epithelioid, rhabdoid and spindled cells arranged in sheets, cords and microcysts within a richly vascularised, myxoid stroma. On immunohistochemistry, the tumor cells were positive for desmin, smooth muscle actin, h-caldesmon, as well as ER and WT1. Gene fusion analysis revealed the presence of a PGR::NR4A3 gene fusion involving exon 2 of PGR and exon 2 of NR4A3. Local recurrence occurred one year after initial excision. Recognition of this rare subtype of gynecologic leiomyosarcoma in the vulva may help refine the classification of unusual vulvovaginal smooth muscle neoplasms.

Background & objectives: Breast cancer is the most common cancer of women. Inferior prognosis in some patients has been attributed to the higher proliferative capability of the tumour. Immunohistochemistry (IHC) for Ki-67, despite being a simple and cost-effective method, has not become a valid tool to evaluate this biomarker. This is ascribed to variation in pre-analytical and analytical techniques, variable expression, hotspot distribution and inter-and intra-observer inconsistency. This study was aimed at defining the analytical and clinical validity of real-time quantitative polymerase chain reaction (RT-qPCR) as an alternative to IHC evaluation. Methods: This study included a total of 109 patients with invasive breast cancers. Ki-67 IHC visual assessment was compared with the mRNA value determined by RT-qPCR. Concordance between both the methods was assessed. Receiver operating characteristic (ROC) curve analysis and Cohen's kappa value with intraclass correlation were performed. Results: The threshold value for Ki-67 by RT-qPCR obtained by ROC curve was 22.23 per cent, which was used to divide breast cancer cases into high proliferative and low proliferative groups. A significant correlation was observed between both the breast cancer groups formed using RT-qPCR threshold as well as median laboratory value of Ki-67 labelling index by IHC. Interpretation & conclusions: The study results showed a significant correlation between the two methods. While IHC is subject to technical and interpretative variability, RT-qPCR may offer a more objective alternative.