A comprehensive examination of Smad4, Smad6 and Smad7 mRNA expression in pancreatic ductal adenocarcinoma.

Background: Smad4, Smad6 and Smad7 are important molecules in TGF-beta pathway, which plays an important role in pancreatic ductal adenocarcinoma (PDAC) biology. Aims : This study examined the expression profiles of Smad4, Smad6 and Smad7 mRNA in patient samples of PDAC and their relationship to Smad protein expression, SMAD4 gene mutations, clinicopathological parameters and patient survival. Settings and Design: Surgically resected, paired normal and tumor tissues of 25 patients of PDAC were studied. Materials and Methods: Protein and mRNA levels were assessed by immunohistochemistry and RT-PCR, respectively. Statistical Methods: Statistical analysis was done using Student's t-test, Pearson's chi-square test, Spearman's Rank Correlation, Pearson's Correlation test and Kaplan-Meier Logrank test. Results: While there was a highly significant difference in the protein levels of all three Smads in tumor as compared to normal samples, mRNA levels were significantly different only for Smad4. Protein levels did not correlate significantly with mRNA levels for any of the three Smads. The mRNA levels of Smad4 and Smad6, Smad4 and Smad7, and Smad6 and Smad7 in tumor samples showed a significant positive correlation. The relationship of Smad4 mRNA expression to SMAD4 gene status and Smad4 protein expression was discordant and there was no significant correlation between mRNA expression and clinicopathological parameters and patient survival. Conclusion : The absence of concordance between SMAD4 gene status, mRNA expression and Smad4 protein expression suggests the presence of other regulatory mechanisms in Smad4 transcription and translation in PDAC.

Direct immunofluorescence of skin biopsy: Perspective of an immunopathologist.

Background: By direct immunofluorescence (DIF), presence of immune complexes in the skin biopsy at various locations such as the dermo-epidermal junction, dermal blood vessels, etc. help to arrive at a diagnosis. Aims: (1) To study the role of DIF in confirmation or exclusion of diseases involving skin vis-à-vis histopathology and clinical diagnosis, (2) to describe the annual spectrum of dermatologic conditions that present to a tertiary referral center and require DIF examination of skin biopsy for confirmation of diagnosis. Methods: A total of 267 biopsies received over a period of 16 months in the Department of Immunopathology were analyzed along with clinical and histopathological details and the correlation between them was studied. Results: DIF was positive in 204 skin biopsies. Of these, 127 biopsies showed good clinico-immuno-histopathological correlation. In 10 cases, only DIF could clinch the diagnosis. In another nine cases, immune deposits were noted, which were unexpected in light of clinical and histopathological diagnosis. The most common skin involvement was seen in vasculitides. DIF was, however, non-contributory in lesions like erythema multiformè, post Kala-azar dermal leishmaniasis, sarcoidosis, lupus vulgaris, pyoderma gangrenosum and prurigo nodularis. Conclusion: The DIF of skin in conjunction with histopathology gives the best diagnostic yield. It is invaluable in confirming the diagnosis of small vessel vasculitides and bullous lesions of skin and can be used as an additional tool to pinpoint the diagnosis of systemic and localized autoimmune diseases involving the skin.

Ectopic Cushing's syndrome: experience from a tertiary care centre.

BACKGROUND & OBJECTIVE: Ectopic secretion of adrenocorticotropic hormone (ACTH) is rare, contributing to 10 per cent cases of endogenous Cushing's syndrome. We describe our experience of about two decades of patients with ectopic Cushing's syndrome (ECS) seen at a tertiary care centre from north India. METHODS: Records of patients with ECS from 1985 to 2006 were retrospectively reviewed that included the presenting manifestations, clinical symptoms and signs, biochemical investigations including plasma cortisol, ACTH and high dose dexamethasone suppression test (HDDST), imaging modalities to localize the non pituitary source of ACTH production, management and follow up of these patients. RESULTS: The study group included 12 patients (7 men) with mean (+/-SD) age at presentation 27.6 +/- 9.5 yr (range 13 to 48 yr) and the mean lag period between onset of symptoms and the diagnosis was 18.3 +/- 12.9 months with a range of 3 to 48 months. The weight loss (41.7%) followed by hyperpigmentation (25%) and infections (16.7%) were the common presenting manifestations. Cuticular atrophy (100%), hypertension (100%), bruise (92%) and proximal myopathy (83%) were the commonest signs. Plasma cortisol at 0800 h was 1267.3 +/- 483.3 nmol/l and at 2200 h was 1214.9 +/- 442.6 nmol/l indicating loss of circadian rhythm. The mean plasma ACTH was 221.1 +/- 55.9 (range 21.7 to 950 pg/ml). All but 2 patients had non-suppressibility of 0800 h plasma cortisol with HDDST. Five patients had thymic carcinoid, 3 had bronchial and one each had islet, hepatic and gut carcinoid and one had medullary thyroid carcinoma as a cause of ectopic ACTH secretion. The mean duration of follow up of these patients was 42.6 months and only two could sustain cure while remaining had either residual or recurrence. INTERPRETATION & CONCLUSION: Ectopic Cushing's syndrome is a rare disease with varied manifestations and associated with increased morbidity and mortality. It presents with clinical features quite similar to classical Cushing's. Surgery with removal of primary tumour was found to be treatment of choice.

Proliferative index in astrocytic tumours.

The accurate grading of astrocytic tumours is of prime importance because it is critical to the patient management and survival/outcome. Although internationally accepted WHO grading system of CNS tumours is based on histological features of H&E stained sections, yet there are cases where differentiation between grade II and grade III is difficult particularly when the biopsy is small. Proliferative index derived from MIB-1 immunostaining has been found to be useful in the distinction between various grades of malignancy. Formalin-fixed paraffin-embedded surgical specimens from 90 cases of astrocytic tumours, 30 each of low-grade astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (grade IV), were immunostained by standard indirect immunoperoxidase technique using MIB-1 monoclonal antibody. MIB-1 labeling index (MIB-1 LI) was calculated. The mean MIB-1 LI values of astrocytomas, anaplastic astrocytomas and glioblastomas were 1.75 +/- 1.5%, 8.74 +/- 6.2%, and 20.54 +/- 12.2% respectively and there was statistically significant difference between grade II and III (Unpaired "t" test, T value 5.907, p value < 0.001) and grade III and grade IV (T value 4.734, p value < 0.001). The statistical analysis also revealed that the mean MIB-1 LI increased with histological grade of malignancy (One way ANOVA test, p value < 0.001). This investigation further reinforces and corroborates the findings that MIB-1 LI is useful tool in assigning grading to the astrocytic tumours and hence in treatment modalities and should be used routinely.

Central neurocytoma: a clinico-pathological study of eight cases.

Central neurocytomas are benign neuronal tumours generally found in the lateral or third ventricles. They are rare, comprising < 1% of all brain tumours. It is frequently confused with other tumours of the central nervous system particularly oligodendroglioma. The present study was done to analyse the histopathological features including immunohistochemical profile of these rare tumours. Eight cases were taken up for the study. Seven of the cases had an intraventricular location and one was located outside the ventricles. Increased intracranial pressure was the most common presenting symptom. Microscopically all tumours were composed of small uniform cells with perinuclear halos and regular round nuclei. The tumour in extraventricular location showed atypical features. Immunohistochemistry showed positivity for neuronal markers. The present series highlights the characteristic clinical and pathological findings of this rare brain tumour. Immunostaining for neuronal markers are essential for distinguishing them from other small round cell tumours of the brain.

Demyelinating disease simulating brain tumours: a histopathologic assessment of seven cases.

BACKGROUND: Demyelinating diseases can present as space occupying lesions with in the brain. It is clinically and radiologically difficult to differentiate them from primary neoplasms. Histopathologically they mimic astrocytic neoplasms closely and identifying these lesions correctly has a profound impact in treatment and prognosis of these patients. AIMS AND OBJECTIVES: The objective was to determine the histopathologic features of such acute focal demyelinating disease that clinically presented as brain tumors. MATERIAL AND METHODS: Seven cases were included for the study. Detailed histopathological examination including stains for myelin and axon were performed. The histopathological keys in arriving at the right diagnoses included a well demarcated lesion that contains uniform distribution of foamy macrophages in the absence of any associated coagulative necrosis, sheets of gemistocytic astrocytes in the white matter that show well-formed processes, perivascular chronic inflammatory cell infiltration and total absence of myelin with relative preservation of axons within these areas. CONCLUSION: The degree of suspicion (clinical, radiological and histopathological) should be high to diagnose these group of lesions. The above-mentioned diagnostic keys should help in arriving at the correct histopathological diagnoses of such cases.

Conservative management of giant hepatic mesenchymal hamartoma.

We report a six-month-old male infant with mesenchymal hamartoma of the liver which was left untreated. Repeat CT scan 1 year later showed regression and calcification of the tumor. The child is well 3 years later.

Maxillary mass as the presenting manifestation of papillary thyroid carcinoma.

A case of follicular variant of papillary thyroid carcinoma presenting with a right maxillary mass is described. This is perhaps the first instance of maxillary metastasis from papillary thyroid carcinoma.

Recurrent intramedullary cervical ependymal cyst.

We report a rare case of high cervical intramedullary ependymal cyst in a young boy. This was associated with atlantoaxial dislocation. After partial removal and marsupialization, the cyst recurred and needed radical total resection.

Histoplasmosis masquerading as tuberculosis: a case report.

Histoplasmosis is not reported very commonly from India. We report a patient in whom the presenting feature was persistent leucopenia and hepatosplenomegaly and was treated as a case of disseminated tuberculosis. At autopsy, this patient showed all features of progressive disseminated histoplasmosis.

Primary central nervous system lymphoma: experience of 46 cases with review of literature.

Primary central nervous system lymphomas (PCNSL) constitutes only 1.0 to 1.5% of all brain tumors. Their incidence has gone up over tenfold in the last 25 years. Though, there has been an association of PCNSL with acquired immune deficiency syndrome (AIDS), yet the increased incidence of PCNSL appears to be real and unrelated to AIDS and organ transplantation. This increased incidence could be because of improvement in diagnostic technology and practice. The outcome remains gloomy despite surgical resection, radiotherapy and intensive adjuvant chemotherapy regimens, as majority of the patients succumb to the disease, with only 30-40% survival in patients under 70 years of age.

Pure non-gestational choriocarcinoma of ovary a case report with autopsy findings.

Primary choriocarcinoma of the ovary (PCO) is rare. This can be gestational (GCO) or non-gestational (NGCO) in origin. It is difficult to differentiate between CGO and NGCO. Non-gestational choriocarcinoma carries a bad prognosis than GCO. We present a case of NGCO who had pulmonary metastasis.

Intestinal metaplasia with dysplasia in pelvis of a horse-shoe kidney.

Intestinal metaplasia of renal pelvis occurs uncommonly and is usually secondary to persistent chronic irritation or inflammation. It is considered to be precursor of adenocarcinoma. A case of horse-shoe kidney which showed extensive intestinal metaplasia and focal severe dysplasia in the renal pelvis is being presented. The metaplastic change in this case is being attributed to persistent inflammation due to more chances of stasis in horse-shoe kidney coupled with renal calculi.

Portal hypertension secondary to Langerhans cell histiocytosis.

We report two children, aged 2 and 2 1/2 years, with multisystem Langerhans cell histiocytosis (LCH). Both were administered chemotherapy, with apparently good response. However, hepatic fibrosis and portal hypertension were detected 5 and 1 1/2 years after therapy, respectively. The first child died after a bout of hematemesis. Hepatic fibrosis can proceed despite apparently successful chemotherapy in LCH.

Vogt-Koyanagi-Harada syndrome following injury-induced progressive vitiligo.

We report a case of Vogt-Koyanagi-Harada (VKH), Syndrome wherein the patient developed ocular symptoms following injury-induced progressive vitiligo with immunologic evidence from the skin biopsy specimen of the vitiligo. This case supports the hypothesis that the cell-mediated immune process against a common melanocyte antigen plays an important role in the development and progression of the disease.

Fatal complications of systemic lupus erythematosus--an autopsy study from north India.

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease with varied clinical manifestations and outcome. It may prove fatal due to disease activity or intercurrent infections. In recent years, earlier diagnosis and better treatment modalities have resulted in a change in the pattern of organ involvement and mode of death in the west. This aspect of the disease is unknown in India. Hence, in this autopsy series of SLE, the organ involvement and cause of death have been studied. Twenty five cases of clinically diagnosed SLE have been analysed retrospectively. Renal involvement was invariably present (96%) with class IV being the commonest lesion in 60% cases. Disease activity was noted in 60% cases. Pleuro pulmonary lesions were seen in 92% cases with infection being the commonest. Pulmonary infections included bacterial pneumonias (13), disseminated tuberculosis (3), pulmonary mucormycosis (1) and aspergillosis (1). Massive pulmonary haemorrhage in 5 cases and acute lupus pneumonitis in one, contributed to the demise of the patient. Vasculitis was evident in single organ in 9 cases, in two or more organs in 3 cases with systemic vasculitis significantly attributing to morbidity in 1 case. Active disease was the cause of death in 60% cases and infection in 40%.

Teratocarcinoma presenting with duodenal metastases diagnosed on endoscopic fine needle aspiration.

Upper gastrointestinal bleed as the first symptom of metastatic testicular tumors is rare. We describe a 17-year-old man who presented with upper gastrointestinal bleed; endoscopic fine needle aspiration cytology from a duodenal mass suggested germ cell tumor, which was later confirmed on histology of the testis.