AMACR Knockout Cell Lysate

Xp11.2-translocation renal carcinoma (TRCC) is suspected when a renal carcinoma occurs in young patients, patients with a prior history of exposure to chemotherapy and when the neoplasm has morphological features suggestive of that entity. We retrieved 20 renal tumours (from 17,500 archival cases) of which morphology arose suspicion for TRCC. In nine cases, TFE3 translocation was confirmed by fluorescence in situ hybridisation analysis. In 9 of the remaining 11 TRCC-like cases (7 male, 4 female, aged 22-84 years), material was available for further study. The morphological spectrum was diverse. Six tumours showed a mixture of cells with eosinophilic or clear cytoplasm in tubular, acinar and papillary architecture. One case was high grade with epithelioid, spindle cell and sarcomatoid areas. Another showed tubular, solid, and papillary areas and foci containing spindle cells reminiscent of mucinous tubular and spindle cell carcinoma. The third showed dyscohesive nests of large epithelioid and histiocytoid cells in a background of dense lymphoplasmacytic infiltrate. By immunohistochemistry, keratin AE1/AE3 was diffusely positive in three tumours, while CK7 strongly stained one tumour and another focally and weakly. CD10 and Pax8 were expressed by eight, AMACR and vimentin by seven, CA-IX by four and TFE3 and cathepsin K by two tumours. Of the two TFE3-positive tumours, one showed polysomy of chromosome 7 and the other of 17; they were VHL normal and diagnosed as unclassifiable RCC. Of the seven TFE3-negative tumours, three showed polysomy of 7/17 and VHL abnormality and were diagnosed as combined clear cell RCC/papillary RCC. One TFE3-negative tumour with normal 7/17 but LOH 3p (VHL abnormality) was diagnosed as clear cell RCC. One TFE3-negative tumour with polysomy 7/17 but normal VHL was diagnosed as papillary RCC, and two with normal chromosomes 7/17 and VHL gene were considered unclassifiable. As morphological features and IHC are heterogeneous, TRCC-like renal tumours can only be sub-classified accurately by multi-parameter molecular-genetic analysis.

Background: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare low grade renal tumour exhibiting characteristic morphological features. We share our experience and discuss briefly, a review of the current literature. Methods: Electronic medical records were searched between January 2005 to January 2017. The histopathology and immunohistochemistry slides were retrieved and reviewed. Results: Eleven cases of MTSCC were identified. Mean age at presentation was 53.9 (age range 41 to 71) years with a slight female preponderance (F: M=6:5). Clinical stage at presentation was: Stage I (4 cases), Stage II (3 cases), Stage III (1 case), and Stage IV (3 cases). The average tumour size was 7.5cm (range 3.5 to 17cm). Microscopically, characteristic biphasic tumour with tubular and spindle cell morphology with variable mucinous stroma was noted in all. The prominent immunohistochemical profile revealed positivity for CK7 (7/8, 87.5%), AMACR (6/8, 75%), AE1/3 (4/4, 100%), CD10 (3/10, 27.3%), and Vimentin (3/3, 100%). Seven patients (Stage I and II) had been treated with nephrectomy, whereas only a diagnostic biopsy was available in four patients who presented with locally advanced disease (n=1) or distant metastasis (n=3) at presentation. The mean follow-up was 37.8 months (range 8 to 96 months), available in 10 out of 11 patients, without recurrence in nine while one died 8 months after diagnosis. Conclusion: MTSCC is an indolent renal cancer with characteristic morphology. However, presentation with locally advanced disease or distant metastasis may be seen in a subset of these patients. This warrants close follow-up in even localized tumors.