A clinicopathologic analysis of 88 lung resections of suspected metastatic carcinomas with proven primaries.

Background: The lung is the most common site for metastatic carcinomas. Very few studies have comprehensively analyzed all pulmonary resections for metastatic carcinomas. Aims and Objectives: To analyze all lung resections for suspected metastatic carcinomas accrued over 10 years to evaluate: The most frequent primary site, The interval between primary tumor diagnosis and lung metastases, and The proportion of inadvertently resected benign lesions, clinicoradiologically mistakenfor metastatic deposits. Materials and Methods: Between 2002 and 2011, 88 pulmonary metastasectomies were done for suspected metastatic carcinomas, which form the basis of this study. Results: In 81 of 88 cases (92%) the diagnosis of metastatic carcinoma was histologically confirmed, whereas 7 cases (8%) were non-neoplastic. The mean interval between primary tumor and metastases was 2.5 years. The primary sites were colorectum (30; 37%), kidney and breast (14; 17.3% each), cervix (9; 10%), salivary gland carcinoma (3), thyroid carcinoma (2), squamous carcinoma (2, one each of mandible and larynx), papillary urothelial carcinoma (2), hepatocellular carcinoma (1), endometrioid adenocarcinoma (1), carcinosarcoma of endometrium (1), adrenocortical carcinoma (1), and neuroendocrine carcinoma (1). The 7 non-neoplastic lesions (8%) histologically revealed tuberculosis (4), bronchopneumonia (2), and aspergillosis (1). Conclusions: Almost three fourths (71.6%) of the metastatic pulmonary resections comprised primaries from colorectum, breast and kidney. The interval between primary tumor and metastases ranged from zero months to 10 years (mean 2.5 years). Tuberculosis was the most common histologic diagnosis among the 8% of the non-neoplastic lesions, which were mistaken for metastatic carcinoma on clinical evaluation.

Epidermal growth factor receptor mutation subtypes and geographical distribution among Indian non-small cell lung cancer patients.

Background: The Medical Oncology Department at Tata Memorial Hospital, the single largest tertiary cancer care center in Asia, receives in-house registered and referral patient samples from all parts of the country. Our recent studies establish 23% EGFR mutation frequency among Indian population. Here, we extend our study and report further analysis of distribution of different types of EGFR mutations in 1018 non small cell lung cancer patient, and its co-relation with clinical parameters and geographical variations across the country. Material and Methods: This study is a retrospective analysis on all the patients who were referred for EFGR testing as a routine service over a 1.5 year period. This was part of standard care. EGFR kinase domain mutations in exon 18-21 were probed by TaqMan probe-based assays in 1018 NSCLC patients. Results and Discussion: While EGFR exon 19 mutations, the most frequent EGFR mutation, were found be higher among non smokers females, we find surprisingly higher incidence of exon 21 mutations among EGFR mutation positive male smokers of Indian ethnicity. Furthermore, as Indian population is known to be composed of a gradient admixture of Ancestral North Indian (with genetic influence from Middle Easterners, Central Asians, and Europeans harboring variant EGFR mutation frequency) and Ancestral South Indians, as a paradox our study indicates comparable EGFR mutation frequency across different geographical locations within India Conclusion: Geographically there is uniform distribution in the EGFR mutation frequency within India. Further more, while exon 19 mutations are predominant among non smokers, higher incidence of exon 21 mutations exists among EGFR mutation positive male smokers of Indian ethnicity.

A year of anaplastic large cell kinase testing for lung carcinoma: Pathological and technical perspectives.

BACKGROUND: An in‑frame fusion protein between echinoderm microtubule‑associated protein‑like 4 (EML4) and anaplastic large cell kinase (ALK) genes is seen in some non‑small cell lung cancer (NSCLC). EML4‑ALK demonstrates constitutive kinase activity. These ALK‑positive lung carcinomas have been shown to respond to ALK kinase inhibitors. ALK gene rearrangement is commonly detected using fluorescent in situ hybridization (FISH). AIMS: To study the pathological features of ALK positive and negative NSCLC and evaluate the causes of uninterpretable FISH results. MATERIALS AND METHODS: This is a retrospective, observational study. The molecular pathology records of patients on whom test for ALK had been performed in a period of 1 year (February 2012 to February 2013) were accessioned. A total 224 cases were identified. Histological features were reviewed. The in situ hybridization was performed using Vysis ALK Dual Color Break Apart Rearrangement Probe (Abbott Molecular Inc.). Signal interpretation under the fluorescent microscope was performed in accordance with College of American Pathologists guidelines. RESULTS: Five patients showed ALK gene rearrangement, 182 were negative and 37 cases were uninterpretable. Five patients with ALK gene rearrangement had a mean age of 48 years and the male to female ratio was 2:3. In the ALK negative cases, the mean age was 54 years and male to female ratio was 3.2:1. Histologically, amongst the rearranged cases, three showed solid pattern, one showed acinar and one showed acinar with signet ring cells on histology. CONCLUSION: The percentage of ALK gene rearrangement was 2.7% (excluding the uninterpretable cases). These ALK positive patients were relatively younger than ALK negative patients. Solid pattern on histology was associated with ALK positivity. In a quarter of the uninterpretable results, the material submitted was fixed and processed outside.

Critical histopathological analysis of 25 dedifferentiated liposarcomas, including uncommon variants, reviewed at a Tertiary Cancer Referral Center.

Background: De-differentiated liposarcomas (DDLSs) are uncommon tumors with a wide histopathological spectrum. Materials and Methods: Over an 8-year period (2003-2011), 25 DDLSs, after review, were critically analyzed for histopathological features. Results: Twenty-five tumors, in 14 men and 11 women (M: F = 1.2:1), with age range of 22-88 years (mean, 53.9), occurred in retroperitoneum (14) (56%), thigh (3) (12%), paratesticular region (3) (12%), chest wall (2) (8%), leg (1) (4%), shoulder (1) (4%), and groin (1) (4%). Tumor size (21 tumors) varied from 7.5 to 25 cm (mean, 17.5). Histopathologically, DD component was high grade in 19 (76%) and low grade in 6 (24%) tumors. Whereas the most common WD component was adipocytic type; the most common DD component was pleomorphic sarcomatous (13) (52%), followed by myxofibrosarcomatous (MFS)-type (6) (24%). Low-grade DD components included MFS (2), fibrosarcoma (2), myogenic/myofibroblastic type (1), and IMFT-type (1). Three tumors displayed meningothelial-like whorls and metaplastic bone formation. Heterologous elements, noted in 11 (44%) tumors, included bone (8) and rhabdomyoblastic differentiation (2). Two tumors displayed homologous differentiation, reinforced with MDM2 staining. S100-P was diffusely positive in WD components (5/7) and focally in DD components (2/9). All patients were treated with surgery, including 10, who underwent adjuvant radiotherapy. Outcomes (16 patients, 64%), over 1-48 months included 10 patients free of disease, 4 died of disease, and 2 patients alive with disease. Conclusions: This study forms the largest documentation of DDLSs, including its wide histopathological spectrum, from our country. Rare cases overlap with pleomorphic liposarcoma. S100-P and MDM2 are useful in substantiating adipocytic differentiation, especially in selected cases. Analysis of adequate tumor sections is vital for correct identification of a DDLS. Surgical excision with adjuvant RT forms optimal treatment.

A clinico-morphological study of 95 cases of sarcomas with metastases to the lungs.

Background: Metastasis of soft tissue sarcoma most commonly occurs to the lungs. There are very few studies on histology of pulmonary metastatectomy and hardly any wherein the histology of the primary tumor has been compared with the metastasis. Aims and Objectives: To review histologically all metastatic sarcomas to lung and compare with the primary where available. Materials and Methods: Ninety-five patients with pulmonary metastases from sarcoma were analyzed histologically for type of sarcoma, chemotherapy-related changes, and changes in adjacent lung. Various clinical parameters like laterality, multiplicity, and interval between primary and metastasis were also studied. Results: Osteosarcoma constituted half of the metastatic sarcomas (48 cases, 50.5%) followed by synovial sarcoma (16 cases, 16.8%) and high grade spindle cell sarcoma-NOS (10 cases, 10.5%). The histology of primary and the metastases was similar in 60% of cases of osteosarcoma. Conclusions: Osteosarcoma is the commonest metastatic sarcoma to the lung. There is often a change to fibroblastic histology in patients of conventional osteosarcoma treated with chemotherapy.

A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult male: A rare case report with review of literature.

Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such cases have dealt with molecular analysis. A 19-year-old boy presented with pain and swelling in his left lower limb of two months duration. He developed acute urinary retention four days prior to his hospital admission, wherein radiological examination unraveled a large soft tissue mass, displacing his pelvic muscles, along with a lytic lesion involving his right pubic bone. Biopsy showed a cellular spindle cell sarcoma, exhibiting hemangiopericytoma-like vascular pattern with focal necrosis. Immunohistochemistry (IHC) showed positivity for vimentin, BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was positive. Diagnosis of a poorly differentiated synovial sarcoma was offered and confirmed with a positive t(X; 18) SYT-SSX2 translocation. This case highlights the value of molecular analysis in diagnosis of a synovial sarcoma at rare sites, especially when IHC results are equivocal and the biopsy material is limited.

Anaplastic large cell lymphoma (ALCL) presenting as primary bone and soft tissue sarcoma--a study of 12 cases.

This study highlights the rare presentation of anaplastic large cell lymphoma as primary bone and soft tissue tumour. Twelve cases were studied. Clinical impression was non Hodgkin's lymphoma in 4 cases, sarcoma in 6 (osteosarcoma-2, Ewing's/primitive neuroectodermal tumour-1, and sarcoma NOS-3), and tuberculosis of thoracic spine in 1 and the last case involving the rib had a differential diagnosis of tuberculosis and NHL. Histology revealed round cells with eosinophilic cytoplasm and pleomorphic nuclei. Immunohistochemically all tumours were CD30 positive and 8 of 9 cases (88.9%) showed ALK-1 positivity. The pleomorphic cytomorphology ofALCL leads to confusion with the more frequent bone and soft tissue sarcomas affecting the musculoskeletal system. A high index of suspicion is necessary to initiate the correct panel of immunohistochemical markers to first confirm the lymphomatous nature of this tumour and to subsequently subclassify. This alone will lead to an accurate recognition of ALCL and the appropriate chemotherapy.

Polyphenotypic peripheral neuroepithelioma occuring in the foot: a case report.

Peripheral neuroepithelioma of the soft tissues is an uncommon member of primitive neuroectodermal tumors. Divergent differentiation and polyphenotypia is known in peripheral neuroepithelioma. We report one such recurrent peripheral neuroepithelioma in an infant which was detected at one month of age, in the foot. Microscopically, it showed tumor cells in nests and lobules with abundant Homer-Wright rosettes. Immunohistochemically, tumor cells were immunoreactive for neural markers but also displayed an aberrant myoid phenotype. The prognostic implications of this anomalous phenotype are unclear as of now, but documentation of this is necessary for possible future references.

Osteoblastoma: a study of 12 cases.

This study comprises of 12 cases of osteoblastoma. There were 8 males and 4 females, with a mean age of 17.8 years. The vertebral column, including the sacrum was the most frequent site (10 of 12 cases). Radiologically the lesions were lytic, well circumscribed and expansile. The histology consisted of intercommunicating osteoid seams lined by plump osteoblasts with numerous intervening ectatic stromal vessels. Despite these characteristic features, the distinction of osteoblastoma from osteoblastic osteosarcoma can at times be very problematic. The lack of lace-like osteoid or sheets of osteoblasts, and inconspicuous mitotic activity are useful distinguishing features. The purpose of this communication is to highlight the microscopic features for the correct recognition of osteoblastoma and its distinction from other osteoid forming bone lesions.

Primary pleuro-pulmonary malignant germ cell tumours.

Lungs and pleura are rare sites for malignant germ-cell tumours. Two cases, pure yolk-sac tumour and yolk sac-sac tumour/embryonal carcinoma are described in young males who presented with rapid progression of respiratory symptoms. The malignant mixed germ cell tumour occurred in the right lung, while the yolk-sac tumour had a pseudomesotheliomatous growth pattern suggesting a pleural origin. Alpha-foetoprotein was immunohistochemically demonstrated in both.

Clinicopathological evaluation of metastatic carcinomas of bone : a retrospective analysis of 114 cases over 10 years.

This is a clinicopathological study of 114 cases of metastatic carcinomas of bone accessioned between 1979 and 1988 at a large cancer hospital. The cases were divided into two groups. The first group comprised of 68 cases (59.64 percent), which included those where the primary was either known (Ia-12 cases), detected after simple investigations (Ib - 18 cases) or detected after extensive investigations (Ic - 38 cases). The lung emerged as the primary source of the metastases in almost half the cases. Hence an X-ray chest should be the basic essential investigation in the workup of skeletal metastasis. The second group comprised of 46 cases (40.35 percent), where the primary remained unknown; 56.5 percent of these were adenocarcinomas. When the histological diagnosis is adenocarcinoma in cases of an occult primary, it is often difficult to pinpoint the primary site after exclusion of organs like breast, prostate, thyroid and kidney.

The neurotropic variant of desmoplastic spindle cell melanoma of the foot--a report of two cases with special reference to its schwanian features.

Melanomas are known to show a wide range of morphological expression. Desmoplastic Malignant Melanoma (DMM) which is a variant of spindle cell melanoma, is often characterised by conspicuous growth in and around nerves which leads to a mistaken diagnosis of malignant Peripheral Nerve Sheath tumours (MPNST). We report two such cases of spindle celled DMM of the foot which displayed neurotropism. The problems and the clinical relevance of distinguishing this variant of melanoma from MPNST is discussed.

Paget's disease of the breast: a study of 43 cases.

Paget's Disease of the breast is caused by spread of duct carcinoma cells along the mammary ducts to the epidermis of the nipple and areola. This is a study of 43 cases of Paget's Disease of the breast. Though only few patients presented with a lump; a carcinoma, either DCIS or IDC or both were found in all cases. The presence of an underlying breast carcinoma in Paget's Disease of the breast suggests that radical mastectomy is the treatment of choice in this condition.

Intrahepatic cholangiocarcinoma: report of a surgically resected case.

We report a middle aged female with intrahepatic cholangiocarcinoma which was resected successfully. Because of an unusual histology, a microscopic diagnosis could not be established pre-operatively. The tumor recurred locally 21 months after surgery. The case is reported mainly for the diagnostic problems it created.