Germline BRCA1 mutation and survival analysis in familial breast cancer patients in Kerala; South India.

Mutations in breast cancer susceptibility gene BRCA1 have been identified in breast or breast/ovarian cancer families from different ethnic background. We analyzed a total of 79 samples for BRCA1 mutation, using Conformation Sensitive Gel Electrophoresis (CSGE) followed by sequencing. The overall survival of BRCA1 mutation carriers was also investigated. BRCA1 mutation was detected in 11 out of the 29 (38%) patients. Four different alterations were detected of three which were novel. A missense mutation in exon 7, 465G>A was detected in 1 patient (9%). Another missense mutation 932 G>A was observed in three patients (27.3%) and a truncation mutation 1027delA, was observed in one patient (9%). The fourth type of mutation (185delAG) which also results in protein truncation was observed in 6 different patients (54.5%). Kaplan-Meier survival analysis revealed a median overall survival of 34 months for BRCA1 mutation positive breast cancer patients and 71 months for BRCA1 negative breast cancer patients. The median overall survival of BRCA1 truncation mutation carriers was 26 months. Our data showed high prevalence of BRCA1 gene mutation among breast or breast/ovarian cancer families in South India and breast cancer patients having BRCA1 mutations were associated with poor prognosis.

Argyrophilic nucleolar organizer regions in the evaluation of tumour progression in the oral mucosa: correlation with tissue pathology.

The present study has analysed the numbers of argyrophilic nucleolar organizer regions (AgNOR) in normal tissues and in premalignant and malignant lesions of the oral mucosa in order to assess their potential as a biological marker for tumour progression. On comparison of AgNOR numbers in different lesions, carcinomas showed the highest number (4.65 +/- 0.98) compared to leukoplakias (2.38 +/- 0.47) and normal tissues (1.53 +/- 0.39). Spindle cell carcinomas and poorly differentiated squamous cell carcinomas had higher AgNOR counts than well-differentiated carcinomas. In various clinically different types of oral leukoplakia, the lowest AgNOR counts were observed in homogenous leukoplakia and the highest in speckled leukoplakia. No significant difference in AgNOR number was observed between non-dysplastic and dysplastic leukoplakia, although a significant difference was evident between dysplastic leukoplakia and normal oral mucosa. Correlating the AgNOR count and tumour progression, a significantly high positive correlation coefficient (r = 0.7969, P = 0.0000) was observed.

Primary malignant mucosal melanoma of the head and neck region: pooled analysis of 60 published cases from India and review of literature.

Malignant melanoma arising in the head and neck mucosa is a rare entity with incidence ranging from 2% to 10%. Because of the lack of data, the biological behaviour of these lesions still remains unpredictable and outcome dismal. We carried out a literature review for cases of mucosal melanoma of the head and neck reported from India and performed a pooled analysis on the available data. A total of 60 cases of head and neck melanomas were reported, of which 46 were in men. Palate and alveolus were the commonest sites. A total of 29 (48.3%) patients had regional node metastasis at presentation while five (12%) had distant metastasis. Three-year overall survival of 27.7% was observed. However, the disease-free survival rates at 3, 5 and 6 years were 39.4%, 39.4% and 13.1%, respectively. Metastasis at presentation and use of adjuvant radiotherapy were found to be the only significant predictors of survival. Malignant mucosal melanoma has aggressive biological behaviour and poor outcome. Radical surgery and adjuvant radiotherapy may provide a better local control and may help in improving survival.

Primary malignant melanoma of the mucous membranes.

AIMS: To investigate malignant mucosal melanoma (MMM), a rare disease and one which has, till lately, remained unrecognized. Incidence of MMM ranges from 2 to 10% in various series. METHODS: We retrospectively reviewed the cases of malignant melanoma treated at the Regional Cancer Centre, Trivandrum, India, over a period of 15 years. RESULTS: A total of 163 cases of melanoma were identified, of which 21 had a lesion in mucosal sites. There were eight cases of upper aero-digestive tract (UADT) melanoma, seven cases of rectal melanoma, five cases with lesions in the vagina and one case with a lesion in the urethra. The mean age of the patients was 52.8 years; mean age of presentation in urogenital and anorectal lesions was similar to overall mean age, while this was lower (47.5 years) for UADT lesions. Almost half of the patients presented with ulcer or nodule with or without pigmentation. Pain was present in three-quarters and vaginal bleeding was present in all cases of vaginal lesions. Almost one-third of the patients failed locally while another third developed distant metastasis during the follow-up period. A 2-year disease-free survival rate of 13.2% (95% CI: 2.2-34.1) was observed, which dropped to 6.6% (95% CI: 0.4-25.7) after 3 years. Survival appeared a little better in UADT melanoma compared to urogenital and anorectal melanoma; however, the difference was not statistically significant. CONCLUSIONS: Malignant mucosal melanoma seems to have an aggressive biological behaviour with a high incidence of local failure and metastasis.

Sarcoma of the oral and maxillofacial soft tissue in adults.

AIMS: Sarcoma occurring in oral and maxillofacial soft tissue is rare. This study was carried out to evaluate the prevalence of oral soft tissue sarcoma and to record its natural history and survival. METHODS: Retrospective analysis of the patients with histologically proven oral and maxillofacial soft tissue sarcoma treated at the Regional Cancer Centre (RCC), Trivandrum, betweeen 1990-1998 was carried out. RESULTS: During this period, ten cases of oral and maxillofacial sarcomas were registered. Three lesions were located on the cheek mucosa, two on the tongue and two on the mandibular alveolus, while there was one lesion each in the parotid region, maxilla and face (NOS). Mean age at presentation was 31.3+/-14.1 years (range 15-54 years). Seven of the patients (70%) were males. There were three cases of rhabdomyosarcoma (RMS), three cases of spindle cell sarcoma and one case each of angiosarcoma, haemangioendothelioma, malignant schwannoma and malignant fibrous histiocytoma (MFH). All the patients were treated with surgery as a primary modality. Median follow-up time was 30 months (range 5-94 months). An overall srvival of 87.5% at 5 years was observed; however, 5-year disease free survival was 60.0% (95% CI 19.5-85.2). CONCLUSIONS: Soft tissue sarcomas are of comparatively less frequent occurrence in oral and maxillofacial soft tissue than in other tissues. A good survival rate can be achieved by multimodality treatment.

Evaluation of surgical excision of non-homogeneous oral leukoplakia in a screening intervention trial, Kerala, India.

It is well established that most invasive oral cancers arise from precancerous lesions such as leukoplakia, erythroplakia and oral submucous fibrosis. One of the approaches for control of oral cancer is to detect oral precancerous lesions early in their development and prevent their malignant transformation to invasive cancer either by chemoprevention or by surgical excision of the lesions, with concurrent control of tobacco and alcohol use and other specific aetiological factors. However, the value of specific approaches such surgery in long-term control of lesions and prevention of malignant transformation is not known. We describe our experience with cold knife surgical excision of 59 cases of non-homogeneous leukoplakia of the oral cavity diagnosed in the context of a community-based oral cancer cluster randomised oral cancer screening trial in Kerala, India. Two-thirds of these revealed dysplasia on histology. After a minimum follow-up of 12 months (range 12-37 months) after surgical excision, 44 (74.8%) were remaining disease free with no evidence of recurrent/new lesions; during follow-up, three (5%) developed new luekoplakic lesions, and six (10.1%) developed recurrent lesions, while six (10.1%) could not be traced after treatment. There was no event of malignant change during follow-up. The proportion of subjects remaining with no evidence of disease at 3 years by Kaplan-Meier method of analysis was 62.1% (95% CI: 0.36-0.87). Accrual and long-term follow-up of large number of surgically treated cases may provide valuable leads to management policies of oral leukoplakia, since, as of now, the added value of specific treatments over and above primary prevention by tobacco and alcohol control remains to be established.

Bone marrow relapse in primary mucinous carcinoma of skin.

Primary mucinous carcinoma of skin is a rare adnexal tumor arising from the eccrine sweat gland. The tumors grow slowly and have low rates of local recurrence and rare chances of distant metastasis. The authors report a 70-year-old man with primary mucinous skin carcinoma who had a relapse in bone marrow 19 months after initial treatment.

Role of sputum cytology in the diagnosis of mediastinal germ cell tumor.

A rare case of germ cell tumor of the mediastinum infiltrating the lung and metastasizing to the supraclavicular lymph node in a 25-year-old male is presented. The patient presented with a history of superior vena cava syndrome and chest roentgenograms revealed an abnormal mediastinum. Primary positive diagnosis was made cytologically on sputum specimens. The peculiar cell type found in the Papanicolaou stained sputum smears were correlated with fine needle aspiration cytology of lung and lymph node, and confirmed the histologic pattern of the tumor metastasizing to the lymph node. To our knowledge, the present case is the first report of a primary mediastinal seminoma (germinoma) infiltrating the lung and diagnosed by sputum cytology. These results suggest the usefulness of sputum examination as an adjunctive diagnostic procedure in the detection of patients with possible lung infiltrated germinal neoplasms.

Osteosarcoma arising in a mature cystic teratoma of the ovary.

A 80-year old woman was found to have an osteosarcoma arising within a mature cystic teratoma of the ovary. To the Author's knowledge, this is the fourth reported case of osteosarcoma arising within a teratoma.

Primary malignant melanoma of the upper aero-digestive tract.

Malignant mucosal melanoma represents 0.3 to 10% of all melanomas. The majority of these lesions arise in the oral cavity or paranasal sinuses. Very few authors report reliable treatment results, however all suggest a uniformly poor outcome. A retrospective analysis of all cases of upper aero-digestive tract melanoma (UADT) treated since 1982 at our centre are presented. During the 15-year period, nine cases of UADT melanoma were identified. Three patients had a lesion in the palate, two in the maxillary alveolus, two in the oropharynx, while one each had a lesion in paranasal sinus and lower alveolus. Mean age was 43.25 years (28-62 years), with a male to female ratio of 1.6:1. Cervical lymphadenopathy was the commonest presenting symptom in seven patients. Radical surgery was carried out in three patients, wide excision in three and radical neck dissection in six, while no surgical intervention was undertaken in two patients. Median follow-up time was eleven months. In four patients, local recurrence occurred, while three developed pulmonary metastasis. One patient was lost to follow-up. We suggest that data from various centres be pooled together in order to carry out a meta-analysis to address the question of optimal treatment for malignant melanoma of the upper aero-digestive tract.

Infrequent loss of heterozygosity of the major tumour suppressor genes in Indian oral cancers.

The loss of heterozygosity (LOH) in tumour suppressor gene loci such as p53, retinoblastoma (rb) and adenomatous polyposis coli (apc) were analyzed in oral cancer tissues with matched controls by employing polymerase chain reaction based/restriction fragment length polymorphism (PCR-RFLP), variable number of tandem repeats (PCR-VNTR) analysis and microsatellite assay. The PCR-RFLP analysis showed an infrequent LOH in rb (17%), p53 (11%) and apc (10%) loci in these cases. The microsatellite assay also revealed only a low frequency of LOH in the microsatellite markers such as TP53 (25%), D5S505 (10%) and D3S1067 (0%) in the same samples. In contrast to the present study, similar studies from Western countries have reported a high frequency of LOH in p53, rb and apc genes in oral cancer tissues. The present preliminary study indicates that the gene aberration by LOH may be an insignificant mechanism in Indian oral cancers with respect to the tumour suppressor genes examined.

Soft tissue sarcoma of the head and neck region in adults.

Soft tissue sarcomas (STS) are rare solid tumours accounting for less than 1% of all malignancies and are very unusual in the head and neck region. Histopathologically diagnosed cases of STS treated at Regional Cancer Centre (RCC). Trivandrum, India, between January 1989 and November 2000 were analyzed retrospectively. Survival analysis was carried out by Kaplan-Meier method and curves were compared using log rank test. A total of 22 cases were seen during the study period. The mean age of the patients was 36.4 years with male-to-female ratio of 2:1. The neck, lower jaw, tongue, cheek, scalp and maxilla were the commonest sites affected. None of the patients had palpable neck nodes or distant metastasis at presentation. All the patients were treated with primary surgical resection and this was followed by adjuvant treatment in 14 cases (63.6%). After a median follow-up of 14.5 months, two patients died, six developed local recurrence, four developed metastatic disease and another patient developed second primary sarcoma. The overall 5-year survival was 80% while the 5-year disease-free survival rate was 24.1%. The majority of the patients failed within first and second year. None of the parameters except grade of tumour (P=0.008) were found to have a significant effect on survival. The overall survival rate for patients with soft tissue sarcoma of the head and neck is good, however, disease-free survival is poor as the majority of these fail within 2 years of completing treatment.

Primary intraosseous carcinoma of the jaw: pooled analysis of world literature and report of two new cases.

Primary intraosseous carcinoma (PIOC) is a rare malignant neoplasm of the jaw. These tumours are believed to arise from the odontogenic epithelium and hence are also referred to as odontogenic carcinoma. A detailed search was made for squamous cell PIOC of the jaw in English literature using Medline Cancer CD. The data obtained were transferred onto dBase software. Two detailed case reports of patients treated at Regional Cancer Centre, Trivandrum during 1996 and 1997 were also included. A pooled analysis was carried out. Survival analysis was carried out using Kaplan-Meier method and log-rank statistics were used for comparing survival. A total of 35 cases were analysed, of which 33 were from published literature. The mean age of the patients at the time of diagnosis was 52.3 years with male to female ratio being 2.5:1. Posterior mandible was the predominant site. The median follow-up time was 28 months. Overall survival at 5 years was 37.8% (95% CI; 14.8-61.0) while the corresponding disease free survival was 29.8% (95% CI; 9.2-54.1). Primary intraosseous carcinoma is a rare tumour of jawbones, characterized by progressive swelling of the jaw, pain and loosening of tooth. The tumour is locally aggressive and metastasizes to regional nodes. The overall and disease free survival is poor with almost 50% patients failing loco-regionally within the first 2 years of follow-up.

Unusual multiple metastases from malignant pleomorphic adenoma of the parotid gland.

A case of malignant pleomorphic adenoma of the left parotid gland which metastasized to the kidney and multiple subcutaneous sites is presented. The patient presented as an acute emergency due to spontaneous rupture of the kidney containing metastasis. All the distant metastatic lesions were confined to the right side of the body.

Parapharyngeal metastasis from papillary microcarcinoma of thyroid: report of a case diagnosed by peroral fine needle aspiration.

A parapharyngeal metastasis from primary thyroid carcinoma is rare and a search of relevant publications disclosed only seven previous reported cases. We describe a 46-year-old man who presented with a left parapharyngeal mass that was subsequently diagnosed by peroral fine-needle aspiration as a metastasis originating from a papillary carcinoma of the thyroid gland. Metastatic thyroid cancer should be considered in the differential diagnosis of a parapharyngeal mass. Fine-needle aspiration cytology is a simple, speedy, and cost-effective method of diagnosis of parapharyngeal masses.

Giant cell tumour of hyoid bone: case report.

Giant cell tumours of bones are uncommon and are usually found in the epiphyses of long bones. They are rare in flat bones (<10%). The tumour has to our knowledge never been described in the hyoid bone, although 18 cases have been reported in the cartilagenous laryngeal skeleton. We report a giant cell tumour of the hyoid bone in a 45-year-old man, which we excised along with the left half of the hyoid bone. It recurred locally one year later and was cured by excision and split course radiotherapy. The patient is disease-free after 30 months of follow-up.

Malignant systemic mastocytosis.

Malignant Systemic Mastocytosis is a very rare condition. Only about less than 40 well documented cases have been reported as per the available literature. The paper presents the case report of a 54 year old male patient who presented with huge hepatosplenomegaly and abdominal lymphadenopathy. Splenectomy specimen was 17 x 16 x 10 cm size with cut surface studded with numerous tiny 1-2 mm nodules. Histologic sections of spleen showed extensive mast cell (typical and atypical) infiltrates. Liver biopsy and abdominal lymphnode biopsy specimens and bone marrow smears also showed similar infiltration by mast cells. Special stains done for non-specific esterase and chloracetate esterase showed strong positivity for mast cells. The results of immunohistochemical and electron microscopic studies are also presented.

Malignant phyllodes tumor.

The study aims to evaluate the survival and prognosis of patients with malignant phyllodes tumor. Between 1982 and 1998, 37 women with malignant phyllodes tumor were treated at the Regional Cancer Center, Trivandrum. Twelve patients were recurrent. Survival was estimated using the Kaplan-Meier method. Patient, disease, and treatment factors were compared using log-rank test. The Cox-proportional hazard model was employed to identify the prognostic factors. Thirty-six patients had surgery. Twenty-five patients received postoperative radiotherapy, and 2 received chemotherapy in addition. The median follow-up was 43 months (range 1-170 months). Eight patients failed locally, and 7 of these were successfully salvaged by surgery. The 5-year overall survival was 74.2% (95% CI, 0.44 to 0.89), whereas 5-year disease-free survival was 59.6% (95% CI, 0.39 to 0.7). The margin of surgical excision was found to be the only independent prognostic factor (p=0.003). However, patients with tumor size more than 5 cm (hazard ratio 2.9) were found to have increased hazard, whereas those receiving adjuvant radiotherapy (hazard ratio 0.6), married women (hazard ratio 0.4), and those women over the age of 35 years (hazard ratio 0.7) showed a decreased hazards. Cystosarcoma phyllodes is a rare malignancy of the female breast. Surgery with adequate margins is the primary treatment. Adjuvant radiotherapy appears to improve the disease-free survival.