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Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a cutaneous CD30-positive lymphoproliferative disorder. The patients usually present with single or multiple cutaneous nodules or papules and about 10% cases present with extracutaneous manifestations, which are predominantly in the form of regional lymph nodal involvement. Visceral involvement especially pulmonary or hepatic involvement in C-ALCL is only rarely described in the scientific literature. Approximately 20%–42% cases show spontaneous regression, about 50% cases may recur; however, C-ALCL generally carries a good prognosis. We present a rare case of primary C-ALCL in a 66-year-old man with regional lymph nodal and hepatic involvement. Differential diagnostic entities are discussed in this report with the review of the literature.

Abstract Malignant schwannomas of the paranasal sinuses are extremely uncommon tumors, as only 18 well-documented cases have been previously published in the English-language literature. We report two new cases of [...]

Limb girdle muscular dystrophy recessive type 1 (LGMDR1, Previously LGMD2A) is characterized by inactivating mutations in CAPN3. Despite the significant burden of muscular dystrophy in India, and particularly of LGMDR1, its genetic characterization and possible phenotypic manifestations are yet unidentified. We performed bidirectional CAPN3sequencing in 95 LGMDR1 patient samples characterized by calpain-3 protein analysis, and these findings were correlated with clinical, biochemical and histopathological features. We identified 84 (88.4%) cases of LGMDR1 harboring 103 CAPN3mutations (71 novel and 32 known). At least two mutant alleles were identified in 79 (94.2%) of patients. Notably, 76% exonic variations were enriched in nine CAPN3exons and overall, 41 variations (40%) correspond to only eight exonic and intronic mutations. Patients with two nonsense/out of frame/splice-site mutations showed significant loss of calpain-3 protein as compared to those with two missense/inframe mutations (P = 0.04). We observed a slow progression of disease and less severity in our patients compared to European population. Rarely, presenting clinical features were atypical, and mimicked other muscle diseases like FSHMD, distal myopathy and metabolic myopathies. This is first systematic study to characterize the genetic framework of LGMDR1 in the Indian population. Preliminary calpain-3 immunoblot screening serves well to direct genetic testing. Our findings prioritized nine CAPN3exons for LGMDR1 diagnosis in our population; therefore, a targeted-sequencing panel of nine exons could serve well for genetic diagnosis, carrier testing, counseling and clinical trial feasibility study in LGMDR1 patients in India.

Primary liposarcoma at vallecula is an extremely rare tumor in hypopharyngeal region. Vallecular liposarcoma shares both clinical and imaging features with other common lesions at this site such as benign lipoma, mucus retention cysts, fibrovascular/ inflammatory polyp and epithelial malignancies extending from adjacent anatomical structures. The two closest mimickers in laryngeal region, atypial lipoma and well differentiated liposarcoma are very difficult to differentiate on laryngoscopic examination and radiological investigations. Dedifferentiation; a poor prognostic histological feature can rarely occur after multiple recurrences but liposarcoma with de novo de-differentiation in larynx is very rare. Herein, we describe a case of liposarcoma with de novo de-differentiation originating from vallecula in a 66 years old male with review of literatures.

The authors report a case of extremely uncommon malignancy of lacrimal gland epithelial-myoepithelial carcinoma. This carcinoma is more commonly encountered in salivary glands and comprises 1% of all salivary gland tumors. Its occurrence in the orbit is very rare with only 6 cases reported in the literature, most of which arose in a pleomorphic adenoma. Epithelial-myoepithelial carcinoma is primarily a tumor of older adults, with a peak incidence in the sixth and seventh decades of life. The present case is the youngest patient reported to date and had no history of preexisting neoplasm in the lacrimal gland. Histological diagnosis of epithelial-myoepithelial carcinoma is challenging because of the similarity with other lacrimal gland epithelial tumors like malignant adenoid cystic carcinoma and benign pleomorphic adenomas.We report a case primary lacrimal gland epithelial-myoepithelial carcinoma in a youngest patient to date. The diagnostic challenges faced in such a case have been discussed.

Malacoplakia is an unusual chronic granulomatous inflammation that commonly occurs in the urinary tract. It is rarely encountered in the head and neck region, and only a handful of such [...]

Primary osteosarcoma of skull base is extremely rare. We present a case of primary osteosarcoma arising in greater wing of sphenoid in a child. Our patient had an incomplete excision after which he received adjuvant chemotherapy and radiotherapy. There was good response to adjuvant chemoradiotherapy and the patient is disease free at a follow-up of 18 months. Treatment of skull base osteosarcomas is difficult, as complete excision is often not possible. To the best of our knowledge, this is the first case of sphenoid wing osteosarcoma in childhood to be reported in literature.

Deleted in liver cancer (DLC1), a Rho GTPase-activating protein, was observed to be differentially expressed in oral squamous cell carcinoma in comparison with normal tissues using tissue proteomics. In the current study, we investigated the clinical significance of loss of DLC1 expression in different stages of development of oral squamous cell carcinoma to determine its potential as a biomarker for oral dysplasia and prognosis of oral squamous cell carcinoma. Immunohistochemical analysis of DLC1 expression was carried out in oral squamous cell carcinoma patients (n=214), dysplasia (n=51), hyperplastic squamous mucosa (n=45), and histologically normal oral tissues (n=80), and correlated with clinicopathological parameters and disease prognosis over 91 months for oral squamous cell carcinomas. Loss of DLC1 expression was observed in oral squamous cell carcinoma (64%), oral dysplasia (31%), hyperplastic squamous mucosa (22%), and normal mucosa (16%). Significant loss of DLC1 expression was observed in oral squamous cell carcinomas as compared with dysplasia (P<0.001, odds ratio=3.8, 95% CI=2.0–7.3), suggesting it may be an important event involved in cancer progression. Among oral squamous cell carcinomas, the loss of DLC1 expression was significantly associated with poor prognosis (P=0.021, hazards ratio (HR)=1.8, 95% CI=1.1–2.9). Multivariate analysis revealed loss of DLC1 (P=0.023, HR=2.1, 95% CI=1.2–3.9) and histopathological grade (P=0.015, HR=1.7, 95% CI=1.1–2.7) to be independent predictors for disease-free survival in oral squamous cell carcinoma patients in comparison with known prognostic factors, viz. tumor stage, nodal status, and overall stage. Loss of DLC1 expression emerged as an important biomarker for predicting patients diagnosed with oral dysplasia at high risk of transformation upon future validation in longitudinal studies. Loss of DLC1 expression is a poor prognostic marker for oral squamous cell carcinoma patients.

To evaluate age-related differences in histopathologic and molecular profile of glioblastomas (GBMs) at various age groups, with special reference to TP53 mutation, epidermal growth factor receptor (EGFR) amplification, EGFR vIII mutant, PTEN deletion, and IDH1 mutation. Agewise GBM incidence was calculated over a period of 5 years (2005 to 2009). Seventy-five GBMs were selected for molecular analysis. Majority of cases were in the age group of 41 to 60 years, and mean age was 43.6 years. Histology of all 75 cases selected for molecular profiling was identical. Primary adult GBMs showed EGFR amplification and PTEN deletion in majority (37.3 and 54.9, respectively). TP53 and IDH1 mutations were rare (11.8 cases each). In secondary GBMs, TP53 (66.7) and IDH1 mutations (44.4) were most frequent. PTEN deletion was seen in 33.3 and none had EGFR amplification. Pediatric GBMs (<18 y) harbored frequent TP53 mutations (46.7) and PTEN deletion in 40. IDH1 mutations and EGFR amplification were absent. The molecular profile of primary GBMs in young adults (19 to 40 y) was distinctly different from that of adults older than 40 years. TP53 mutation was present in 20 cases. The frequency of EGFR amplification (13.3) and PTEN deletion (33.3) was significantly low (P=0.028 and 0.046, respectively). IDH1 mutation, which is rare in primary adult GBMs, was present in 40 of cases. Molecular heterogeneity exists within GBMs of different age cohorts. The molecular profile of GBMs in young adults is distinctly different. Thus, there is a strong need for further studies in various age groups to provide guidelines for therapeutic targeting.

Various molecular markers have been used for diagnosis, management and prognostication of gliomas. Neurocytomas are close morphological mimics of oligodendrogliomas. While combined 1p/19q deletion has been used as a molecular signature of oligodendroglial tumours, it has also been variably reported to occur in neurocytomas, especially those in extraventricular locations (EVN). In recent studies, presence of IDH1 mutation has shown immense prognostic significance in glial tumours including oligodendrogliomas, but its role in neurocytoma pathogenesis remains unexplored. In this study, EVN cases were analysed for histomorphological features, IDH1 mutation using an antibody for specifically detecting mutant IDH1R132Hprotein, and 1p/19q deletion by fluorescence in situhybridisation (FISH) assay.

Combined loss of chromosome arms 1p and 19q in oligodendroglial tumors has become a powerful predictor of prognosis and treatment response, and hence clinical testing for their detection is widely used nowadays. Polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) analysis and fluorescence in-situ hybridization (FISH) are the 2 important relatively common clinical molecular diagnostic techniques used for this purpose and they have their unique advantages and limitations. The preference of methodology used depends on local expertise and existing laboratory capabilities. However, there is no consensus on which methodologic approach has a better potential. The objective of the study was to compare the accuracy, reliability, and feasibility of FISH and PCR in detecting the 1p and 19q LOH status. Using the PCR-based method, a LOH analysis was performed on 30 oligodendrogliomas and 10 glioblastomas using fresh-frozen tissue and peripheral blood as control. A FISH assay using paraffin blocks was performed on all the cases. Concordance for 1p and 19q was found in 92.5 (37 of 40) and 82.5 (33 of 40) cases, respectively. The relative advantages and limitations of both the techniques are analyzed and discussed. The main issue pertains to the use of the best technique in large clinical trials whose results are translated to patient care services. Unless the technique used is correct, the results of clinical trials and their correlations may be somewhat questionable.

Summary Majority of the cerebellopontine angle (CPA) tumors are acoustic neuromas, while bulk of the non-acoustic tumors are formed by meningiomas and epidermoid cysts. Primary paraganglioma is a rare tumor in this location, with only two such cases having been reported in the literature, till date. Recently, a case has been described wherein a paraganglioma was apparently arising as a primary lesion in the cerebellar hemisphere. We report another case of an intracranial paraganglioma of the CPA in a 40-year-old female, which did not have any vascular attachment but had focal cerebellar extension.

Abstract Apoptosis and cell proliferation occur simultaneously in tumour tissue with tumour suppressor gene, p53 being one of the key players in the complex relationship between these two key phenomena. We, as well as several other groups, have earlier demonstrated the association of p53 immunopositivity with increased degree of cell proliferation in astrocytic tumours. Here we have studied the extent of apoptosis in 62 primary human astrocytic tumours [25 Diffuse Astrocytoma (DA), 9 Anaplastic Astrocytoma (AA) and 28 Glioblastoma multiforme (GBM)] in relation to tumour grade, proliferative status and p53 protein expression. Apoptosis was measured by the TUNEL assay while, cell proliferation (MIB-1 index) and p53 protein immunoreactivity were evaluated by immunohistochemical staining using MIB-1 and DO-1 monoclonal antibodies respectively. The apoptotic index (AI) was greater in GBM than in AA or DA, and more in tumours with p53 immunopositivity than in those without. The most striking observation was the strong correlation between Apoptotic index (AI) and proliferation index (PI) in p53 negative GBM (r=0.766, P < 0.005). However this was not observed in p53 +ve GBM or in low grade DA either p53 positive or negative. Taking p53 negativity in IHC as evidence of a functional gene/protein, this extends the link between proliferation and apoptosis, hitherto observed only in cultured cells with functional p53, to a subset of solid tumours.

Abstract

Abstract Over the last two decades, an increase in the incidence of PCNSL cases has been reported in the West, both among immunosuppressed and immunocompetent patients. The present study was undertaken to assess the trend of incidence of PCNSL cases in India. To the best of our knowledge, only a single such report is available from India. All biopsy proven PCNSL cases obtained from the Neurosurgical databases of two large referral hospitals, one in Northern India (AIIMS, New Delhi) and another in Southern India (NIMHANS, Bangalore) from the period 1980 to 2003, were reviewed. Immunophenotyping was done and relevant clinical details collected. Appropriate statistical analysis was done to assess any change in trend of incidence or age at presentation. PCNSL cases constituted 0.95% and 0.92% of the total intracranial neoplasms at AIIMS and at NIMHANS, respectively. The mean age for cases diagnosed at AIIMS was 44.35 years, while that for NIMHANS was 39.51 years. Statistical analysis to evaluate any change in trend either of incidence or of age at presentation, over the study period, did not reveal any significant change. All the cases occurred in immunocompetent patients, except one case of HIV positive at NIMHANS, and one case of renal transplant at AIIMS. Frontal lobe was the most common site of involvement. Majority of the cases were diffuse, high grade, large cell lymphoma, B-cell immunophenotype. Thus, this multicentric hospital based study did not reveal any increase in incidence of PCNSL cases in India over the past 24 years. Further, in contrast to the West, majority of the cases in this Indian study were immunocompetent and a decade younger than in the West. The association of PCNSL with HIV/AIDS has been low in India, possibly due to early death in AIDS on account of opportunistic infections.

Subependymal giant cell astrocytomas (SEGAs) are relatively rare tumors but occur commonly in the setting of the familial syndrome of tuberous sclerosis complex (TSC). In view of its varied morphology, i.e. resemblance to astrocytic and ganglion cells, its histogenesis remains controversial. We studied 23 cases of SEGA, 19 from our own institute and 4 from NIMHANS, Bangalore. These 19 cases of SEGAs were collected over a period of 23 years (1979 to 2001), and accounted for 0.16% of intracranial tumors and 0.51% of all gliomas reported at our center. The majority of patients presented with visual disturbances (19÷23, 82.6%) in the form of decreased vision (60.8%) and blindness (21.7%), generalized tonic clonic seizures (43.4%) and focal motor seizures (4.37%). Age ranged from 4 to 37 years (mean 13.2 years) with male predominance (M:F 2.2:1), and the duration of symptoms varied from 1 month to 96 months (mean 17.2 months). Lateral ventricular involvement was the most common site (91.3%), followed by the third ventricle (8.6%). Nine patients (39.1%) had stigmata of tuberous sclerosis (6 at the time of diagnosis and 3 in the follow-up period). Two patients died due to surgical complications, while the rest were alive and well in the follow-up period ranging from 3 to 264 months (mean 37.1 months). Two patients experienced recurrences, one two years and another 22 years after surgery. Microscopic examination showed varied histology consisting of sweeping bundles of spindle cells, gemistocyte and ganglion-like cells with interspersed inflammatory cell component. The inflammatory cell component on special staining turned out to be an admixture of mast cells and T lymphocytes. Six cases showed areas of necrosis and/or mitosis, but were not indicative of aggressive nature of this tumor. Immunoreactivity for GFAP, NF, S-100, NSE and synaptophysin indicates that this is a hybrid tumor with glial and neuronal differentiation. None of the tumors was immunopositive for HMB-45. The significance of the presence of T lymphocytes and mast cells is not clear. It could be related to tumor immunology and may indicate a favorable prognosis.

This is a study of 64 cases of recurrent astrocytic tumors of all four WHO grades wherein a comparative evaluation of initial vs. recurrent tumor was done with respect to histological grading, MIB-1 labeling index (LI) and apoptotic index (AI). The aim was to identify factor/s that could influence interval to recurrence and/or malignant progression. Recurrence was noted in all grades and upon recurrence, 93.3% of grade II (low grade diffuse) astrocytomas and 63.6% of grade III anaplastic astrocytomas underwent malignant progression. However, none of the Grade I tumors showed evidence of malignant progression. Though interval to recurrence varied considerably, there was a correlation with histological grade of the initial tumor in that grade I and II tumors had a significantly longer mean interval to recurrence (43 months and 54.8 months respectively) as compared to grade III and IV (glioblastoma multiforme) tumors (17.6 and 12.8 months respectively). The interval to recurrence was also longer for grade II and III tumors which showed progression on recurrence (55.3 months for Grade II → Grade III; 54 months for Grade II → Grade IV and 20.6 months for Grade III → IV) as compared to tumors which recurred to the same grade (12.5 months for Grade III → Grade III and 12.8 months for Grade IV→ Grade IV). A statistically significant inverse correlation of MIB-1 LI with interval to recurrence was noted. Higher the MIB-1 LI, shorter was the interval to recurrence. Further a cut off MIB-1 LI value of 2.8% could be proposed in predicting recurrence free survival. Interestingly, MIB-1 LI of grade II tumors, which had progressed to grade IV was significantly higher than MIB-1 LI of grade II tumors which had progressed to grade III. Thus, this study establishes the potential role of MIB-1 LI of the initial tumor in determining interval to recurrence. However, apoptotic index has no role in predicting either interval to recurrence or malignant progression.

Lipomatous ependymoma is a recently described entity and only 3 cases of this variant have been reported in the literature. We report 5 cases of this rare variant of ependymoma. Patients’ age ranged from 4 years to 45 years and, interestingly, all of them were males. Two tumors were supratentorial in location, 2 in the fourth ventricle and 1 was intramedullary. Microscopically all of them showed the classical histology of ependymoma along with lipomatous differentiation. The lipomatous component was composed of cells with a large clear vacuole pushing the nucleus to the periphery and giving a signet ring cell appearance. This component demonstrated positivity for GFAP and S-100 protein thereby confirming its glial lineage. Three of the 5 tumors were high grade (WHO-grade III), had a high MIB-1 labelling index (MIB-1 LI) and showed recurrence on follow-up. However, 2 were low grade (WHO grade II) and patients are free of disease till the last follow up.

A 38-year-old man, a chronic smoker, presented to us with a large left upper lobe mass lesion and left-sided pleural effusion. After resection, a residual mass remained. On histopathologic examination, a diagnosis of pleiomorphic rhabdomyosarcoma stage III of the lung was made. Chemotherapy using IRS (Intergroup Rhabdomyosarcoma Study) IV protocol with radiation therapy (RT) at week 9 was planned. The tumor progressed within 6 weeks of chemotherapy to involve the diaphragm and the pericardium (inoperable disease). Chemotherapy was abandoned, and we referred the patient to receive RT, which the patient refused; and he died of progressive disease 1 month later. The poor response to chemotherapy suggests that alternative treatment modalities including RT/second-look surgery or novel chemotherapeutic strategies should be tried in such a case.

Tuberculous involvement of the pituitary gland is rare. We report a unique case of a composite lesion consisting of pituitary adenoma and intrasellar tuberculoma. A 24-year-old lady presented with features of acromegaly and amenorrhea. Serum growth hormone levels were found to be raised. Radiological investigations were consistent with a pituitary adenoma. Decompression of the lesion was done through trans-sphenoidal approach. Histological examination revealed a growth hormone secreting pituitary adenoma in association with a granulomatous lesion suggesting of pituitary tuberculoma. No other evidence of tuberculosis was found in the brain or spinal cord. This type of dual pathology has been reported only once in the earlier literature.