Ahitagni Biswas

Atypical teratoid rhabdoid tumor of the brain: case series and review of literature

IntroductionIntracranial atypical teratoid rhabdoid tumor is an uncommon malignancy with a dismal outcome. Commonly misdiagnosed over the decades as primitive neuroectodermal tumor of the brain, it has dramatically different biological behavior.DiscussionWe herein report a case series of five patients diagnosed and treated as atypical teratoid rhabdoid tumor of the brain in a major cancer center in north India. We have also analyzed the clinical, histopathological, and radiological features and the therapeutic options of this enigmatic tumor.

Spinal intradural primary germ cell tumour—review of literature and case report

BackgroundPrimary spinal cord germ cell tumour is a rare tumour. We herein review the tumour characteristics, associated risk factors, treatment policy, and patterns of failure of primary intradural germ cell tumour.MethodWe conducted a PUBMED search using a combination of keywords such as “spinal germ cell tumor,” “germinoma,” “extradural,” “intradural,” “intramedullary,” “extramedullary,” and identified 19 cases of primary spinal germ cell tumour. Clinical features, pathologic characteristics, and treatment details of these patients including status at follow-up were noted from respective case reports. We also describe a case of a young Indian patient of intradural extramedullary germ cell tumour treated with a combination of surgery, chemotherapy, and radiotherapy.FindingsThe median age at presentation was 24 years. The most common location of the tumour was thoracic (40%). β-HCG overproduction was noted in 40% of the patients. Most patients were treated with a combination of surgery, radiation therapy, and systemic chemotherapy. Median follow-up was 16.5 months. Recurrence was observed in 10% of the patients, all in β-HCG over-producing tumours. The illustrative case was a 28-year male, presenting with pain in lower back and both lower limbs for 2 months. Magnetic resonance imaging spine showed an inhomogeneous hyperintense soft tissue mass at L2-L4 spinal level. He was treated with complete surgical excision and four cycles of chemotherapy with BEP regimen following a histological diagnosis of non-seminomatous germ cell tumour. Palliative irradiation to the lumbar spine was given on progression at 3 months. The patient eventually succumbed to his condition, due to compressive transverse myelitis possibly due to cervical cord metastasis.ConclusionLimited surgery followed by upfront radiation therapy and adjuvant chemotherapy is the optimal management of this rare group of tumour. Omission of radiation therapy from the treatment armamentarium might engender local recurrence and spinal dissemination at first failure.

Bleomycin induced flagellate erythema: Revisiting a unique complication.

Bleomycin induced flagellate dermatitis is a rare and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in common clinical practice. We herein describe a case of a 22-year-old Indian male with Hodgkins lymphoma, Ann Arbor stage IIBEX developing flagellate dermatitis following 1(st) cycle of chemotherapy with ABVD regimen. The diagnostic dilemma in the illustrative case underscores the importance of awareness and prompt identification and treatment of this dermatological toxicity in limiting morbidity in patients undergoing bleomycin based combination chemotherapy. In patients having severe rash, bleomycin should be expeditiously discontinued. Omission of bleomycin does not compromise the treatment outcome in the majority of patients with Hodgkins lymphoma.

Primary gliosarcoma – clinical experience from a regional cancer centre in north India

Aims. We intended to assess the clinicopathological features and treatment outcome in patients of primary gliosarcoma, a rare malignant brain tumour. Materials and methods. Medical records were reviewed and data collected on primary gliosarcoma over an 8-year period (2002–2009) from the departmental archives. Overall survival (OS) was analysed by Kaplan–Meier method. Results. Seventeen patients met the study criterion (male:female = 9:8). Median age and performance status at presentation were 50 years and Karnofsky performance scale (KPS) 70, respectively. Symptoms of raised intracranial tension (in 100%) and motor impairment (in 64.7%) were commonly observed. Tumour location was frontal in four patients, temporal in three, parietal in three, thalamic in one, multilobed in five and multicentric in one. All patients underwent maximal safe surgery (total excision-10, near-total excision-2, subtotal excision and decompression-5). On histopathology, all tumours showed biphasic pattern, glial component positive for glial fibrillary acidic protein (GFAP) and mesenchymal component positive for vimentin and reticulin. Atypia, mitoses, necrosis and endothelial proliferation were identified in the glial component. Post-operative radiotherapy (median dose – 60 Gy/30#/6 weeks) was used in 15 patients (88.2%). Concurrent and adjuvant chemotherapy with temozolomide (TMZ) were used in two patients depending upon affordability. After the completion of treatment, 35.3% patients were asymptomatic, 23.5% had symptomatic improvement, while 41.2% deteriorated. Salvage therapy for local recurrence was used in three patients (temporal lobectomy-1; total excision-1; TMZ+ bevacizumab-1). At last follow-up (FU), eight patients were alive, seven patients dead and two patients lost to FU with symptom. Median overall survival in the evaluable patients (N = 15) was noted to be 8.27 months (6 month survival 60.76%). Conclusions. Primary gliosarcoma, a variant of glioblastoma poses clinical challenge because of rarity, poor prognosis and limited experience. In our centre, principle of therapy is akin to that of glioblastoma – surgery followed by radiation along with concurrent and adjuvant TMZ. However, chemotherapy is often cost-prohibitive in our setting as mirrored by limited use (17.6%). Median survival of only 8.27 months in our series is in concert with the existing survival result of primary gliosarcoma in world literature (6.25–11.5 months).

Metabolic and body composition changes after six months of highly active antiretroviral therapy in northern Indian patients

This study was carried out to evaluate the metabolic and body composition changes among northern Indian patients receiving combination antiretroviral therapy (cART). We prospectively studied 68 adult patients at the All India Institute of Medical Sciences hospital, New Delhi. The CD4 count, blood pressure, anthropometry, metabolic and bioelectrical impedance data were collected prior to initiation of cART and six months later. The participants had a mean age of 35.9 years and 57 (84%) were male. Hypertension developed in 10.3%. The body mass index, waist circumference, total body fat and lean body mass increased significantly. The total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol, triglyceride and non-HDL-c increased significantly (P < 0.0001). Diabetes mellitus developed in 2.1%; metabolic syndrome in 19.1% (according to International Diabetes Federation criteria) and 25% (National Cholesterol Education Program – Adult Treatment Panel III criteria). Prolonged survival in the cART era may thus predispose these patients to adverse cardiovascular consequences. To the best of our knowledge, this is the first study of metabolic abnormalities in northern Indian HIV/AIDS patients receiving cART. Larger studies across India with long-term follow-up periods are required to confirm these preliminary findings. We also recommend that frequent biochemical monitoring should be performed in such patients.

Osseous Hodgkin's lymphoma—review of literature and report of an unusual case presenting as a large ulcerofungating sternal mass

Osseous involvement in Hodgkins lymphoma is uncommon. The most common location is vertebral, primarily in the thoracolumbar region, followed by pelvis, ribs, femur, sternum, clavicle and skull in decreasing incidence. We herein illustrate the salient features of the disease citing a case of a disseminated Hodgkins lymphoma presenting as a large ulcerofungating sternal mass mimicking chronic tubercular osteomyelitis. The case report highlights the importance of clinical suspicion of unusual presentation of lymphohematopoietic tumors of the bone especially in developing countries, where chronic granulomatous disease is preponderant.

Atypical teratoid/rhabdoid tumors: challenges and search for solutions

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central nervous system tumor commonly affecting children <3 years of age. It roughly constitutes 1%–2% of all pediatric central nervous system tumors. Recent data show that it is the most common malignant central nervous system tumor in children <6 months of age. Management of this aggressive tumor is associated with a myriad of diagnostic and therapeutic challenges. On the basis of radiology and histopathology alone, distinction of AT/RT from medulloblastoma or primitive neuroectodermal tumor is difficult, and hence this tumor has been commonly misdiagnosed as primitive neuroectodermal tumor for decades. Presence of a bulky heterogeneous solid-cystic mass with readily visible calcification and intratumor hemorrhage, occurring off-midline in children <3 years of age, should alert the radiologist toward the possibility of AT/RT. Presence of rhabdoid cells on histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal, and neuroectodermal markers along with loss of expression of SMARCB1/INI1 or SMARCA4/BRG1 help in establishing a diagnosis of AT/RT. The optimal management comprises maximal safe resection followed by radiation therapy and multiagent intensive systemic chemotherapy. Gross total excision is difficult to achieve in view of the large tumor size and location and young age at presentation. Leptomeningeal spread is noted in 15%–30% of patients, and hence craniospinal irradiation followed by boost to tumor bed is considered standard in children older than 3 years. However, in younger children, craniospinal irradiation may lead to long-term neurocognitive and neuroendocrine sequel, and hence focal radiation therapy may be a pragmatic approach. In this age group, high-dose chemotherapy with autologous stem cell rescue may also be considered to defer radiation therapy, but this approach is also associated with significant treatment-related morbidity and mortality. Novel small molecule inhibitors hold promise in preclinical studies and should be considered in patients with relapsed or refractory tumor.

Primary amelanotic melanoma of the breast: combating a rare cancer

BackgroundMalignant melanoma is the foremost cause of metastasis to the breast from extramammary solid neoplasm. However primary melanoma of the breast is a distinct rarity. Primary melanoma involves the skin and less commonly the glandular parenchyma of the breast.MethodWe herein describe a case of primary amelanotic melanoma of the breast parenchyma in a 32-year-old female managed with a combination of surgery, adjuvant radiotherapy and immunotherapy.ConclusionThis case report aims to increase awareness of unusual neoplasms of the breast which might require a different surgical and adjuvant therapeutic approach.

Treatment of squamous cell carcinoma of external auditory canal: A tertiary cancer centre experience

OBJECTIVE Carcinoma of external auditory canal (EAC) is a rare disease with variable management strategies and prognosis. We aimed to analyze treatment modalities, prognostic factors and survival outcomes in patients of squamous cell carcinoma of EAC treated at our institution. METHODS Forty-three patients of squamous cell carcinoma of EAC were analyzed for clinical presentation, stage, surgical procedures and radiotherapy (RT) modalities employed. Stell and McCormick staging system was used for staging of the patients. Progression free survival (PFS) was estimated by the use of Kaplan-Meier product-limit method. Log rank test was used to assess the impact of prognostic variables on PFS. Multivariate analysis was performed using the Cox hazard regression model. p value of <0.05 was considered significant for all statistical analysis. RESULTS Median age was 56 years (range: 12-84 years). Male to female ratio was 31:12. Stage was T1, T2 and T3 in 2, 17 and 18 patients respectively. Sixteen patients underwent surgery. Thirty-six patients received RT (14 received definitive RT, 11 had post-operative RT and 11 had RT with palliative intent). Eight patients (16%) received chemotherapy (5 received concurrent with RT, 2 had adjuvant and 1 had neo-adjuvant chemotherapy). Nine patients (of 11 patients) achieved a complete response (CR) and 2 achieved a partial response (PR) after surgery plus post-operative RT. Nine patients and 5 patients respectively achieved CR and PR after definitive RT (with or without concurrent chemotherapy). Of the 11 patients who received palliative RT, 2 had very good objective response (>50%) and 7 patients had PR to palliative RT. After a median follow-up of 16 months, median PFS for the entire cohort was 14 months. Two-year PFS rates were 85.7%, 46.9% and 0% for patients treated with surgery and post-operative RT, definitive RT and palliative RT respectively. On univariate analysis, higher stage (p=0.05) and facial nerve palsy at presentation (p=0.0008) were significant predictors of inferior PFS. CONCLUSION Patients with carcinoma of EAC present mostly in advanced stage at our centre. Combined higher stage (T3) and facial nerve palsy at presentation portend poorer outcome. Combined modality treatment with surgery and radiotherapy should be advocated and palliative RT remains a reasonable treatment option in patients with advanced incurable disease.

Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation, MGMT Promoter Methylation, and TERT Mutation Status: Experience from a Tertiary Care Center in India.

This study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases. Combinatorial assessment of MGMT and TERT emerged as independent prognostic markers, especially in the IDH1 wild-type GBMs. Thus, within the IDH1 wild-type group, cases with only MGMT methylation (group 1) had the best outcome (median PFS: 83.3 weeks; OS: not reached), whereas GBMs with only TERT mutation (group 3) had the worst outcome (PFS: 19.7 weeks; OS: 32.8 weeks). Cases with both or none of these alterations (group 2) had intermediate prognosis (PFS: 47.6 weeks; OS: 89.2 weeks). Majority of the IDH1 mutant GBMs belonged to group 1 (75%), whereas only 18.7% and 6.2% showed group 2 and 3 signatures, respectively. Interestingly, none of the other genetic alterations were significantly associated with survival in IDH1 mutant or wild-type GBMs. Based on above findings, we recommend assessment of three markers, viz., IDH1, MGMT, and TERT, for GBM prognostication in routine practice. We show for the first time that IDH1 wild-type GBMs which constitute majority of the GBMs can be effectively stratified into three distinct prognostic subgroups based on MGMT and TERT status, irrespective of other genetic alterations.