Clinicopathological Profile of Muscle Diseases Presenting the Adult Population in Northern India: Preliminary Analysis in a Limited Resource Setting.

BACKGROUND: Muscle diseases are of various types, viz., muscular dystrophies, inflammatory myopathies, myotonic disorders, congenital myopathies, and metabolic myopathies. They all present with muscle weakness, be it proximal or distal. The assessment of muscle biopsy with the help of enzyme histochemistry, histopathological, and immunohistochemical methods is an essential component in the diagnosis of neuromuscular disorders. The authors outline brief data on muscle diseases prevalent in the North Indian region. METHODS: Muscle biopsy was done, and the biopsy was freshly frozen in liquid nitrogen and sections were taken on a cryostat. Slides were then stained with hematoxylin and eosin (H&E), modified Gomori trichome (MGT), nicotinamide adenine dinucleotide hydrogenase (NADH), and succinic dehydrogenase (SDH) stains. Further specific immunohistochemistry tests were also done. RESULT: Out of n=16 cases, three cases were diagnosed as Becker's muscular dystrophy, two cases were diagnosed as inflammatory myopathy, four cases were diagnosed as Facioscapulohumeral muscular dystrophy, and one each case of dysferlinopathy and alpha sarcoglycanopathy. CONCLUSION: Muscle diseases can cause different levels of physical disability and thus it is important to diagnose at the appropriate time to ensure proper treatment.

Evaluation of HER2Neu Status in Periampullary Cancers in Tertiary Care Centre in Northern India: A Three-Year Retrospective Study.

Background Periampullary carcinoma is a heterogeneous group of malignancies, and despite advances in treatment, its mortality rate remains high. A better understanding of the disease and factors influencing its course and potential therapeutic targets is imperative for improving its overall outcome. Through comprehensive cytogenetic analysis, it has been established that the development of periampullary carcinogenesis involves specific chromosomal aberrations, dysregulation of oncogenes, and suppression of genes in a multistep progressive manner. Our study aimed to evaluate the expression of human epidermal growth factor (HER2Neu) in periampullary cancers using immunohistochemistry and fluorescent in situ hybridization. Material and methods This was a retrospective study in which all consecutive cases of periampullary carcinoma diagnosed over a period of three years were evaluated. HER2neu expression was analyzed using immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH). Histopathological evaluation was performed according to the College of American Pathologists (CAP) protocol. Results Twenty patients were diagnosed during the study period. On histomorphologic analysis, most cases (n=17) were diagnosed as well-differentiated adenocarcinomas, the most common subsite being the ampulla of Vater and pathological staging as pT2N0Mx. On IHC, no overexpression of HER2Neu was reported in any case, but FISH analysis revealed one point of amplification with HER/centromere enumerator probe (CEP) ratio>2. Conclusion HER2Neu evaluation in periampullary carcinoma has limited value; thus, it could have a restricted therapeutic role.

Pigmented dermatofibrosarcoma (Bednar tumour) of scalp.

Pigmented dermatofibrosarcoma protuberans (DFSP) also known as Bednar tumour is a very rare variant of DFSP which is considered to be of intermediate grade along with the presence of melanin-containing dendritic cells. Only a handful of cases have been described in the literature so far. It is centred around the dermis or subcutis and can pose a diagnostic challenge by being confused with other pigmented lesions of the skin. We hereby report one such unusual case of a man in his late 20s presenting with swelling over the forehead for the past 7 years. Hence a diagnosis of pigmented DFSP should always be considered while reporting pigmented subcutaneous lesions with spindle cell morphology.

BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer.

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George's Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (≥3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of "BRCAness" in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP-ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

Clinicopathologic Correlation of CD44 + /CD24 - Expression in Breast Cancer: a Report from Tertiary Care Medical University in India.

CD44 + /CD24 - phenotype has been associated with stem cell-like characteristics with enhanced invasive properties, radiation resistance, and with distinct genetic profiles suggesting a correlation to adverse prognosis in western literature. The aim of this study was to study CD44 + /CD24 - phenotype as an adverse prognostic marker in Indian breast cancer patients. N = 61 breast cancer patients included in a tertiary care facility in India were evaluated for receptor studies (estrogen receptor ER, progesterone receptor PR, Herceptin antibody Her2 neu receptor, CD44 & CD24 stem cell markers). CD44 + /CD24 - phenotype was statistically related to adverse factors like estrogen and progesterone receptors non-expression, her 2 neu expression, and triple-negative breast cancer. Of the 39 patients with ER-ve status, 33 (84.6%) were found to have CD44 + /CD24 - phenotype and 82.5% of all the CD 44 + /CD24 - patients were ER negative (p = 0.001). Thirty-four (75.5%) of the PR-ve patients showed the CD44 + /CD24 - phenotype, and of all the CD 44 + /CD24 - patients, 85% of were PR negative (p = 0.006). Thirty-six (75%) of Her-2-Neu + ve were CD44 + /CD24 - . Approximately 90% of the Her 2 Neu patients expressed CD44 + /CD24 - and 76.9% of all the triple-negative patients were found to be CD44 + /CD24 - expression (p = 0.001). CD44 + /CD24 - had a significant association with adverse prognostic factors like stage of disease, hormonal receptor status, and molecular subtypes in Indian breast cancer patients like the Western data.

Nodular Hidradenocarcinoma, Trichelemmal Carcinoma and Squamous Cell Carcinoma with Clear Cell Changes: Pitfalls of Biopsy Diagnosis of Skin and Adnexal Tumours.

Skin and Adnexal tumours are a group of benign and malignant tumours whose basic diagnosis relies on histopathology. A single tumour may show more than 1 appendageal differentiation. Morphologic distinction between benign and its malignant counterpart is of utmost importance as it affects the treatment and prognosis of patient. We have described 3 cases who presented in our university hospital, in which final resection pathological diagnosis differed from initial core biopsy interpretation. The authors have made an attempt to provide a brief overview of diagnostic overlap existing between nodular hidradenocarcinoma and tumours of clear cell histology. Salient morphologic features differentiating cylindroma or trichilemmal carcinoma from squamous cell carcinoma have also been discussed. Final diagnosis is paramount for adjuvant management and prognostication of the patient in a clinical setting.

Management of Refractory Aseptic Subtrochanteric Non-union by Dual Plating.

BACKGROUND: Subtrochanteric fractures are challenging to treat because of their anatomical and biomechanical behaviours. Non-unions of this region become much more difficult to treat because of the previous surgical scar, fibrosis, mal-reduction, presence of an implant, compromised soft tissue, and osseous vascularity, bone-mass loss etc. The aim is to provide a stable mechanical environment by PF-LCP, augmented by LCP (dual plating) where biology can work uneventfully. Biology is re-initiated by decortication (shingling) and autologous cancellous bone graft. METHODS: Twelve cases of failed aseptic subtrochanteric non-union either with intact or broken implant were included in this study in a period of 3 years from August 2016 to July 2019. The interposing fibrous tissue resected in patients with mal-aligned fragments. The mechanical stabilization is achieved by orthogonal dual plating. PF-LCP on lateral and 4.5 mm LCP anteriorly, decortication, and cancellous graft applied before applying for the anterior plate. Patients were encouraged for a toe-touch walk with walking-frame from 3rd post-operative day. Functional outcomes were assessed using Parker Mobility Score (PMS). RESULTS: All fractures united in 7 ± 1.53 months. ROM at the knee remained unchanged but improved at the hip after revision surgery. Average PMS improved to 7.58 from pre-revision 1.75 validating the efficacy of this protocol. CONCLUSION: Adequate stability by dual-plate construct and re-initiation of cellular and biochemical processes by decortication and cancellous bone-graft reunited ununited subtrochanteric fractures. This particular combination of plates and decortication has not been employed earlier as per our review of the literature. AIM: To offer a new paradigm for the management of surgically failed subtrochanteric non-unions.

Giant congenital melanocytic nevus associated with lipoma in an Indian man.

Congenital melanocytic nevus is a inborn melanocytic proliferation either present since birth or soon afterward and shows characteristic histopathological features comprising proliferation of benign melanocytes and extension of nevus cells into the deep reticular dermis and subcutis. We report the case of a 35-year-old male patient who presented with a progressively enlarging soft tissue mass in bilateral flank region. High-resolution ultrasound imaging showed multiple lipomatous masses within the soft tissues on the either flank region. Subsequent excision of the soft tissue mass showed a well-circumscribed lipomatous lesion with diffuse infiltration by benign appearing melanocytes within the fat lobules established by immunohistochemistry, which was positive for HMB45 and S100. This case serves to illustrate the initial diagnostic challenge in a male patient as well as the plasticity of the neural crest cells.