Imatinib Inhibits GH Secretion From Somatotropinomas

Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line.Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/β) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways.Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-β (PDGFR-β; P < 0.009 and P < 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01) and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-β pathway.Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas

The spectrum of renal diseases observed in native renal biopsies in a single North Indian tertiary care center

We analyzed the spectrum of biopsy-proven renal disease in a single tertiary care center in North India from 2007 to 2016. A total of 420 biopsies were analyzed. Patients were excluded if clinical details were unavailable or if either the histopathology core or the IF core was inadequate. In the final analysis, 359 biopsies were included. All clinical, laboratory, histopathological, and immunofluorescence (IF) findings were recorded in each case. The usefulness of IF in reaching a definitive diagnosis was also analyzed. The patients were in the age range of 2–94 years; 23.1% were children and 76.9% were adults. Males (60.4%) outnumbered females (39.6%) in all the disease categories except lupus nephritis (LN). Primary glomerular diseases (PGDs) (n = 297, 82.7%) were more common than secondary glomerular diseases (SGDs) (n = 46, 12.8%) and tubulointerstitial diseases (n = 16, 4.5%). The most common PGD was focal segmental glomerulosclerosis (FSGS) (23.4%), followed by minimal change disease (17%) and membranous nephropathy (12.5%), whereas the most common SGD was LN, seen in 9.2%. In the present study, IF helped in reaching the final diagnosis in 44.3%. The entities in which IF was most useful in reaching the final diagnoses were FSGS (31.5%) and IgA nephropathy (14.5%). The final pathological diagnosis correlated with the first clinical possibility in 207 of 359 (57.7%) cases. This 10-year study provides descriptive data and highlights the changing pattern of renal disease possibly due to an increased awareness and referral to higher centers

Cutaneous metastases of internal malignancies: A clinicopathologic study

Background: Secondary tumor deposits in the skin represent advanced malignancy and are of uncommon occurrence. The clinical presentation of these lesions is variable, and the clinical impression is rarely correct, except in cases of known primary malignancies. Aim: To summarize the clinical and histopathological findings in biopsy-proven cutaneous metastases. Methods: The present study has analyzed 14 cases of cutaneous metastases from internal malignant neoplasms, excluding hematolymphoid neoplasms. The clinical parameters analyzed include presentation of deposits and their relation to the primary tumor. The histological features of cutaneous metastases were compared with the primary tumors and the frequency of common features in them were evaluated. Results: Cutaneous metastases from internal organ malignancies showed a prevalence rate of approximately 2%. Eight cases (56%) presented as primary manifestations of the tumor; biopsy evaluation in these cases suggested the possible primary tumor site and triggered further evaluation and imaging studies. Four patients, undergoing treatment for a known malignant tumor, had recurrence of the tumor in the form of cutaneous metastatic deposits. In the remaining two patients, cutaneous metastases of the tumor appeared simultaneously with the primary neoplasm and represented a higher stage of malignancy. Conclusions: Skin biopsy findings were significant in all cases. The morphological patterns of cutaneous metastases corresponded with the primary tumors and their evaluation helped localize unknown primary malignancies. In cases with known primaries, cutaneous metastases upstaged the malignancy and affected the prognosis

ACNE Agminata - Report Of 3 Cases

Acne agminata or lupus miliaris disseminatus faciei is a chronic granulomatous inflammatory disorder-affecting adults of both sexes which terminates spontaneously with scarring. Histopathologically, the papules show granulomas consisting of epithelioif cells, Gaint cells, with or without caseation necrosis along with periappendigeal lymphomononuclear cell infiltrate in the dermis. The exact aetiopathogenesis of this condition is still unknown. We report 3 cases of this uncommon dermatoses recently seen by us