SMARCA4/BRG1-Deficient Non-Small Cell Lung Carcinomas: A Case Series and Review of the Literature.

CONTEXT.­: Somatic mutations in SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and/or BRG1 (Brahma-related gene 1) loss identifies a subset of non-small cell lung carcinomas (NSCLCs) lacking alterations in EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase), and ROS1 (ROS proto-oncogene 1) genes. Preliminary observations suggest responsiveness to immunotherapy and targeted therapies. OBJECTIVE.­: To study BRG1 loss in NSCLCs and elucidate the clinicopathologic profile of such SMARCA4-deficient NSCLCs. DESIGN.­: Non-small cell lung carcinomas diagnosed during 6 years were subject to immunohistochemistry for BRG1 and BRM (Brahma). Tumors with BRG1 loss were stained with antibodies against thyroid transcription factor 1 (TTF-1), p40, cytokeratins, hepatocyte paraffin 1 (Hep Par 1), Sal-like protein 4 (SALL4), CD34, SRY-box 2 (SOX2), chromogranin, synaptophysin, p53, integrase interactor 1, ALK, and ROS1. EGFR mutation testing was performed by polymerase chain reaction-based method. RESULTS.­: Among 100 NSCLCs tested, 4 cases (4%) showed BRG1 loss. The histology ranged from solid adenocarcinomas (n = 1) to large cell/poorly differentiated carcinomas (n = 3) with clear cell cytology in 2 cases. All showed loss/reduction of BRM with variable cytokeratin and SALL4 expression, and were negative for TTF-1, p40, Hep Par 1, ALK, ROS1, and EGFR mutations. CD34 and SOX2 were negative in all 4 cases. Isolated BRM loss was common (21%), distributed across all NSCLC subtypes including squamous cell carcinomas and a hepatoid adenocarcinoma. CONCLUSIONS.­: BRG1 loss occurs in a subset of TTF-1/p40-negative poorly differentiated NSCLCs. Identification and follow-up will clarify the prognosis, diagnostic criteria, and potential for therapeutic personalization.

Isolated Laryngeal Leishmaniasis: A Diagnostic Dilemma.

Isolated laryngeal Leishmaniasis is a rare entity in the Indian subcontinent. We describe a case of a 45 year old male with hoarseness and noisy breathing. Patient's initial histological and serological workup was inconclusive. Final biopsy findings (suggestive of Leishmania donovani), positive rK-39 serology and his native place being Bihar (endemic for Leishmaniasis) led us to the diagnosis. He was treated with high dose liposomal Amphotericin B to which he responded well. This case report highlights the importance of remaining aware of rare infectious causes of laryngitis. Timely diagnosis and intervention are crucial.

Melanotic neuroectodermal tumour of infancy presenting as a lytic lesion in femur: a rare tumour at a rare site with an unusual behaviour.

Melanotic neuroectodermal tumour of infancy (MNTI) is an uncommon tumour, predominantly occurring in head and neck, mostly maxilla, but also in skull and mandible. Although a benign lesion, it is known to recur in 15%-27% of cases, and rarely, may undergo malignant transformation. We present a case of a 5-month-old female patient, who presented with a gradually progressive swelling in the right thigh. On imaging, an osteolytic lesion was seen, involving the metadiaphysis of shaft of right femur. A biopsy was performed, on which diagnosis of MNTI was made. MNTI is rarely seen in extremities. To the best of our knowledge, only six cases have been reported in femur, the present case being the seventh. The tumour showed spontaneous regression on follow-up in our patient, which has rarely been described. A knowledge of characteristic morphology and immunohistochemistry is the key to differentiate it from other tumours.

Spectrum of cytomorphological features of extranodal NK/T-cell lymphoma, nasal type.

OBJECTIVE: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive extranodal lymphoma of NK-cell or T-cell lineage. Its clinical features overlap with those of several sinonasal mass lesions. While the histopathological features are well described, diagnosis is often difficult, owing to presence of extensive coagulative necrosis, so that repeated biopsies may sometimes be necessary for correct diagnosis. Literature on cytological findings of ENKTL is limited. METHODS: Cytomorphological features of cases of histologically confirmed ENKTL having corresponding cytology samples were reviewed retrospectively, to identify distinctive features that could possibly suggest this entity. RESULTS: Aspirates from five patients were studied: four from cervical nodes, one from cheek swelling and one from pleural fluid. Two aspirates were reported as positive for malignancy, two as atypical lymphoid proliferation and one was non-diagnostic. Pleural fluid was reported as malignant, favouring a diagnosis of carcinoma. On cytology, aspirates showed medium to large cells with folded, indented nuclei and abundant pale cytoplasm, some with tongue-like cytoplasmic protrusions. A distinctive feature was presence of large loose clusters of tumour cells with arborising capillaries running through them. Interestingly, necrosis was consistently absent. Subsequent biopsies from palate (three cases) and nasal masses (two cases) confirmed the diagnosis of ENKTL. CONCLUSIONS: Suspicion of ENKTL on cytology is crucial for timely diagnosis to avoid diagnostic delay, especially when only highly necrotic biopsy samples are available. Awareness of distinctive cytomorphological features is required to make fine needle aspiration an effective diagnostic tool for initial diagnosis and for evaluation of possible recurrences.

Small Cell Neuroendocrine Carcinoma: A Rare Nasopharyngeal Malignancy with Aggressive Clinical Course.

Primary small cell neuroendocrine carcinoma is uncommon in head and neck region, with occasional cases in nasopharynx. Distinction from other round cell tumors is imperative to ensure optimal patient management. We present a case of a 30-year-old woman who presented with a rapidly growing nasopharyngeal mass.

Ichthyosis Uteri Associated with Endometrial Adenocarcinoma: A Case Report.

The replacement of the entire or extensive parts of endometrial lining by stratified squamous epithelium is a rare entity known as ichthyosis uteri. It is considered to be a benign condition but may be associated with dysplastic changes and primary squamous cell carcinoma of the endometrium. Its association with endometrial adenocarcinoma is very rare. The aetiology of this condition is not clearly understood till date. We report a case of ichthyosis uteri associated with endometrial adenocarcinoma in a 70-year-old female who presented with complaint of per-vaginal bleeding for six months and underwent hysterectomy after being diagnosed with endometrial carcinoma. Microscopic examination of sections revealed endometrioid adenocarcinoma International Federation of Gynaecology and Obstetrics (FIGO) Grade 3 along with extensive replacement of the endometrial lining by stratified squamous epithelium, consistent with ichthyosis uteri. Although ichthyosis uteri is considered benign and its malignant potential is yet to be established, its association with endometrial malignancies, both squamous and adenocarcinoma, necessitates extensive sampling of the uterus if any focus of squamous metaplasia is identified in a hysterectomy specimen, to rule out a co-existing carcinoma.