Detection of microsatellite alterations in bronchial washings in squamous cell lung cancer: the first study from India

BACKGROUND: In recent times, the possibility of detecting lung cancer using microsatellite alterations (microsatellite instability and loss of heterozygosity) in DNA of bronchial washings has been explored. However, no data regarding the presence of microsatellite alterations in lung cancer are available from India, a country which contributes significantly to the lung cancer burden of the world. METHODS: Bronchial washings as well as tumor specimens obtained on bronchoscopy were analyzed for the presence of loss of heterozygosity (LOH) and microsatellite instability (MSI) using the D3S1300 microsatellite marker on chromosome 3p and the TP53 marker on chromosome 17p. RESULTS: The sensitivities of the TP53 and D3S1300 loci in bronchial washings were 35% and 45% (combined 50%), respectively, which was significantly better than conventional cytology (positive for malignant cells in 15%). The presence of these microsatellite alterations was not related to the age, cumulative smoking exposure or smoking status (current or former) of patients. CONCLUSION: Microsatellite alterations, particularly LOH, occur in a significant proportion of Indian patients with squamous cell carcinoma of the lung.     

Langerhans cell histiocytosis presenting as a limbal nodule in an adult patient

PURPOSE: To report a case of Langerhans cell histiocytosis presenting as a limbal nodule. DESIGN: Observational case report. METHOD: A 26-year-old man presented with a superior limbal mass. On clinical examination, an infiltrative/neoplastic lesion was suspected, and a differential diagnosis of limbal amyloidosis, limbal fibrous histiocytoma, lymphoma, and juvenile xanthogranuloma was made. There was no other associated ocular or systemic abnormality. An excision biopsy was performed. RESULTS: The histopathology and immunohistochemical staining examination established the diagnosis of limbal Langerhans cell histiocytosis. CONCLUSION: To the best of our knowledge, this is an unusual presentation of Langerhans cell histiocytosis, and although rare, Langerhans cell histiocytosis should be included in the differential diagnosis of a limbal mass.     

Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade > or =3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%-27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/ anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic.     

Pathologic changes in breast cancer following neoadjuvant chemotherapy: implications for the assessment of response

Neoadjuvant chemotherapy (also known as preoperative or primary chemotherapy) is the treatment of choice for patients with locally advanced breast cancer. One of the main advantages of neoadjuvant chemotherapy is that it allows for assessment of pathologic response to treatment. Clinical and radiologic evaluations of response to neoadjuvant chemotherapy are based on change in tumor size, and the correlation with pathologic response is often inaccurate. Pathologic evaluation of tumor size remains the gold standard for evaluation of residual tumor after chemotherapy. Chemotherapy-induced histomorphologic change is commonly observed in posttreatment resection specimens and can contribute to the less-than-perfect correlation between the clinical assessment of tumor size and the pathologic measurement. Therefore, accurate histologic mapping to the macroscopic and radiologic appearance of the tumor bed is necessary. Cytopathologic changes are also common in residual cancer cells after neoadjuvant chemotherapy and have uncertain clinical relevance. There is a role for the development of new histologic approaches to augment the pathologic and clinical assessment and provide information on the differential response, particularly for tumors in which less than pathologic complete response is achieved.     

Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality

There is considerable interest in the biology and therapeutic potential of adult stem cells from bone marrow stroma, variously referred to as mesenchymal stem cells or marrow stromal cells (MSCs). Human MSCs can expand rapidly in culture, but the rate of expansion and the yields of multipotential progenitors are inversely related to the plating density and incubation time of each passage. We have defined conditions for optimizing the yields of cultures enriched for early progenitors. Also, we developed a simple method for assessing the quality of the cultures by phase-contrast microscopy and image analysis or by forward light scatter in a flow cytometer. The cells expanded most rapidly on day 4 after plating, with a minimum average doubling time of about 10 hours for cells initially plated at 10 or 50 cells/cm(2). After plating the cells at 1 to 1000 cells/cm(2), the cultures underwent a time-dependent transition from early progenitors, defined as thin, spindle-shaped cells (RS-1A), to wider, spindle-shaped cells (RS-1B), and to still wider, spindle-shaped cells (RS-1C). Assays for adipogenesis demonstrated that the adipogenic potential of cultures was directly related to their ability to generate single-cell-derived colonies and their enrichment for RS-1A cells. In contrast, cultures enriched for RS-1B cells showed the greatest potential to differentiate into cartilage in a serum-free system. The results indicate that, when preparing cultures of human MSCs, it is necessary to compromise between conditions that provide the highest overall yields and those that provide the highest content of early progenitor cells.     

Myofibroblastoma of the male breast: a diagnostic problem on fine-needle aspiration cytology

Myofibroblastoma is an uncommon neoplasm of the male breast. Herein, we describe the cytologic features seen in the fine-needle aspirate of a 45-year-old man. The smears were cellular with intimate association of tumor cells with extracellular matrix material. The cells were spindle to polygonal and were without significant atypia. Numerous mast cells were observed. Nuclear grooving was present only occasionally, although this was conspicuous histologically. The presence of hyaline bands in between tumor cells, another interesting feature, was appreciated retrospectively. This neoplasm was initially misinterpreted as a malignant soft tissue tumor. Awareness of the cytologic features coupled with mammography should prevent a misdiagnosis of this tumor.     

Prevalence of HIV infection in psychiatric patients attending a general hospital in Tamil Nadu,south India

An anonymous, unlinked study was conducted to detect antibodies to HIV-1 or HIV-2 infections in 1,160 consecutive, newly registered, adult psychiatric outpatients at a general hospital in South India to determine whether psychiatric patients presenting to general hospitals are a population at high risk for HIV infection and should be routinely screened. The seroprevalence of HIV infection (12/1160; 1.03%; 95% CI = 0.4-1.6%) did not approximate rates expected of a high-risk group compared to the national (0.7%) or regional community (1.8%) prevalence. It did not differ significantly from HIV seroprevalence in non-psychiatric patients (233/35450; 0.7%; 95% CI = 0.57-0.74%) who were systematically screened (relative risk = 1.57; 95% CI = 0.88-2.80) during the same period, but was greater than the seroprevalence in healthy blood donors (0.5%; p = 0.02; relative risk = 2.15 95% CI = 1.17-3.95). Non-psychiatric patients were also more likely to be HIV infected than blood donors (p = 0.02; relative risk = 1.37; 95% CI = 1.05-1.78). These findings have implications for HIV testing policies among psychiatric and non-psychiatric patients presenting to general hospitals in India.