Cytodiagnostic Dilemma in a Lung Mass as the First Presentation of Testicular Mixed Germ Cell Tumor Metastasis.

Testicular mixed germ cell tumors (TMGCTs) are rare malignant tumors comprising of two or more types of germ cell tumors. Their onset may be undetectable and the patient may first present with symptoms of metastasis. We hereby report a case of a young male who presented with respiratory discomfort and had no symptoms of primary testicular tumor. CT-guided FNAC lung revealed mainly necrotic, keratinous debris with a focus of chondromyxoid stroma. Differential diagnoses of components of teratoma, squamous cell carcinoma and inclusion cyst was considered. FNAC was reported out for the possible presence of teratoma components. Retrospectively, physical examination and subsequent USG revealed testicular tumor. The case led to a diagnostic dilemma as the patient presented with no prior history suggestive of metastasis from testicular mixed germ cell tumor. The aim of the current case report is to alert the pathologists and clinicians about this uncommon clinical presentation and diagnostic relevance of FNA. It highlights that FNA lung revealing keratinous material should always be searched for the possibility of teratoma component.

Peritoneal Malignant Mesothelioma Metastasizing to Lymph Node in Young Male-a Case Report.

Peritoneal malignant mesothelioma is an uncommon neoplasm with a poor prognosis. We hereby report a case of a 20-year-old male, first diagnosed on biopsy with axillary lymph node metastasis. He presented with abdominal pain and axillary lymphadenopathy, with no history of asbestos exposure. CECT showed peritoneal thickening and ascites. Ascitic fluid cytology showed reactive morphology. The diagnosis of metastatic deposits of malignant mesothelioma was made on histopathology and confirmed by immunohistochemistry. Tumor cells were immune-reactive for CK 5/6, calretinin, D2-40, and WT1 and negative for TTF1, CK 20, and CD 3. This case report has two important highlights-(i) unusual presentation with axillary lymph node metastasis leading to diagnostic dilemma in a young male with no asbestos exposure history and (ii) confirmatory diagnostic role of IHC in Peritoneal malignant mesothelioma.

Recommendations of apex health bodies remain localized: not in conformity with international implementation policy for urological disorders.

In developing/underdeveloped countries there is still a great burden of adverse drug reaction (ADR), morbidity and mortality because of poor regulations and implementation of preventive measures. These countries try to copy/follow guidelines from international bodies like American Urology Association (AUA), European Association of Urology (EAU), AGS, UMC and WHO irrespective of their country of origin and success in implementation. Although recommendations of these organizations are obligatory, yet these are taken as the gold standard for good clinical practices. This manuscript highlights difference in view point of various apex health organizations in formulating health policies for prevention, diagnosis, treatment and ADR monitoring for urological disorders. Lacking role of regulatory bodies in implementation of existing policies may lead to potentially inappropriate medication and produce a great economic burden. This analysis has prompted us to recommend that these apex bodies should have better coordination in producing a single value document, make it mandatory part of curricula in medical schools for better awareness, awareness campaigns and separate reporting column in ADR form.

Updates on "Cancer Genomics and Epigenomics".

The field of "Cancer Genomics and Epigenomes" has been widely investigated for their involvement in cancer to understand the basic processes of different malignancies. The aggregation of genetic and epigenetic alterations also displays a wide range of heterogeneity making it quite necessary to develop personalized treatment strategies. The complex interplay between DNA methylation and chromatin dynamics in malignant cells is one of the major epigenetic mechanisms that lead to gene activation and repression. Hence, each tumor needs to be fully characterized to satisfy the ideas of personalized treatment strategies. The present article addresses various aspects of genome characterization methods and their potential role in the field of cancer genomics and epigenomics.

Correlation of Hormone Receptor and Human Epidermal Growth Factor Receptor-2/neu Expression in Breast Cancer with Various Clinicopathologic Factors.

BACKGROUND: A significant development in the breast carcinoma management is the correlation between the presence of hormone receptors in the tumor and response to hormonal therapy and chemotherapy. Human epidermal growth factor receptor-2/neu (Her-2/neu) overexpression also serves as a very useful parameter to predict response to herceptin. AIM OF STUDY: The study was conducted to correlate immunohistochemical expression of markers such as estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu with various clinicopathologic parameters. MATERIALS AND METHODS: The study included 509 cases of breast carcinoma over a period of 5 years (from May 2009 to May 2014). Immunohistochemistry (IHC) for ER, PR, and her-2/neu was performed. RESULTS: ER positivity was observed in 42.8% (218/509) cases, PR positivity in 31.8% (194/509) cases whereas her-2 neu positivity was seen in 40.7% (203/509) cases. Triple marker (ER, PR, and Her-2/neu) negative cases were 23.6% (120/509) cases. ER and PR expression was found to have a statistically significant correlation with tumor grade. Statistically significant correlation was observed between tumor size and tumor grade and her-2/neu expression. Her-2/neu expression showed statistically significant association with tumor stage. As the tumor grade increased, the proportion of triple-negative cases went on increasing, which was statistically significant. CONCLUSION: IHC has an increasingly important prognostic role in determination of factors that affect clinicopathologic features. Nevertheless, the results of this large series showed different patterns of findings with respect to clinicopathologic features.

Association of MTHFR (C677T) Gene Polymorphism With Breast Cancer in North India.

BACKGROUND: Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP) C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP) in the pathogenesis of breast cancer among the North Indian women population. MATERIALS AND METHODS: Genotyping was performed by polymerase chain reaction (PCR) using genomic DNA, extracted from the peripheral blood of subjects with (275 cases) or without (275 controls) breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups. RESULTS: The distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different (P = 0.007 and P = 0.005, respectively) between the control and the case subjects. CONCLUSION: This study shows an association of the CT genotype and the T allele of the MTHFR (C667T) gene with increased genetic risk for breast cancer among Indian women.

Circulating Tumor Cells in Breast Cancer: Correlation with Clinicopathological Parameters, Hormone Profile and MicroRNA Polymorphisms.

OBJECTIVE: Circulating tumor cells are isolated tumor cells in the peripheral blood that serve as important prognostic indicators for many kind of tumors. The study was conducted to know the rate of detection of circulating tumor cells among breast cancer patients in comparison with benign breast diseases and control subjects and to know the association between CTC positivity and various clinicopathological parameters, hormonal profile and microRNA polymorphisms. MATERIAL AND METHOD: In the present case control study, we included 182 healthy controls, 108 cases of benign breast disease and 114 breast carcinoma cases. Various clinicopathological details of cases were recorded. Immunohistochemistry was performed for estrogen (ER) and progesterone receptors (PR) and Her-2 neu. Circulating tumor cells were analyzed using flow cytometry (EpCAM, CK, CD45). Genotypic frequency of micro RNA polymorphisms was determined by PCR-RFLP assay. RESULTS: Circulating tumor cell positivity was observed in 11/114 (9.64%) breast cancer cases but absent in benign and control groups, and was significantly associated with tumor size, histologic type, tumor grade, metastasis and skin infiltration (p < 0.05). Circulating tumor cell positivity did not show any correlation with the immunohistochemical profile. No significant associations between pre-miRNA genetic variations miR-196a2 C/T (rs11614913), miR-146a G/C (rs2910164) and miR-499 T > C (rs3746444) polymorphisms and circulating tumor cell positivity were observed. CONCLUSION: The flow cytometry protocol for detection and molecular characterization of circulating tumor cells is a time and cost-effective technique, suitable for routine clinical use. However, more elaborate studies are needed to establish the findings as our study was limited by small sample size.

Morphometric evaluation and clinical correlations in pediatric malignant small round cell tumors.

AIMS: Nuclear size increases in malignant tumors and reflects DNA content, ploidy and proliferation index. Present study investigated if the nuclear morphometry could differentiate histomorphologically similar paediatric malignant small round cell tumors on hematoxylin and eosin stained sections for diagnostics in a resource poor setting. SETTINGS AND DESIGN: All the consecutive malignant pediatric tumors received in Pathology Department from other faculties of King George's Medical University and also those referred directly to Pathology Department from other hospitals of city/other cities during 3 years period were recorded. MATERIALS AND METHODS: Morphometric analysis was done in 22 confirmed (by higher ancillary techniques) but histomorphologically difficult to differentiate round cell tumors. All sections were analyzed by cell images from six different areas, using Leica Q win 500 images software. RESULTS: Nuclear measurements were obtained for retinoblastoma (RB) (nine cases), neuroblastoma (five cases), Wilms tumor (WT) (three cases), rhabdomyosarcoma (three cases), malignant hemangiopericytoma (one case) and non-Hodgkin lymphoma (one case). Among the RBs, maximum mean nuclear area percent (24.93) was seen in a case with nerve involvement and metastasis, followed by cases with only nerve involvement (21.60) and smallest area (16.57) was in non-nerve involving, nonmetastatic cases. All five cases of neuroblastoma had almost similar mean nuclear area percent (18.05-18.29). WT case with metastasis had higher nuclear area (21.25) than nonmetastatic (19.47). Amongst all the tumors, minimum value (14.93) was seen in malignant hemangiopericytoma. CONCLUSION: Morphometric evaluation in paediatric malignant round cell tumors have generated useful data, and needs further multicentric confirmation for implementation.

Grading systems in the cytological diagnosis of breast cancer: a review.

In developing countries, diagnosis of breast carcinoma is still made on fine-needle aspiration cytology (FNAC). For the resource-poor settings, FNAC is cheaper, less invasive and can sample different areas of the lesion compared with core needle biopsy. The role of breast FNA is usually limited to just categorize the lesion as benign or malignant. Prognostic information from cytomorphology, conveyed to the clinician depends upon the cytopathologist's way of formatting the report. PubMed-based literature search collated the information from articles describing the architectural and cytological features studied on breast aspiration smears. This review focuses on cytomorphological features and the different grading systems with their strengths, short-comings, and practical applicability. Eight worldwide articles proposing new methods of grading the cytological smears from breast cancers were published between 1980 and 2006. All the grading methods were developed for the most common type of breast cancer, that is, infiltrating duct carcinoma (not otherwise specified) type, and most of the workers used Papanicolaou-stained smears for the purpose of grading. Moreover, if interpreted carefully FNAC smears can convey information on most of the histological features. Hence, in developing countries, the focus should be on extracting the maximum information from cytological smears, so that a more precise "surgical pathology" type diagnosis can be given, instead of merely reporting as benign or malignant. Among all the discussed grading systems, we suggest grading system by Howell would be most appropriate and closest to the accepted histologic grading system as it applies Scarff-Bloom-Richardson histological grading system with modifications on FNA smears. We recommend it to be followed by all cytopathologists, in order to bring uniformity in the reporting of breast FNAs for grading the malignant lesions.

Erythrodermic mycosis fungoides with hypereosinophilic syndrome: a rare presentation.

Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma (CTCL). It is generally associated with an indolent clinical course and characterised by well-defined clinicopathological features. Although rare, CTCLs constitute 65% of all cutaneous lymphoid malignancies, of which 50% are patients with MF. The erythrodermic variants of MF, a malignancy of mature, skin homing and clonal T lymphocytes, usually present in mid to late adulthood. Association with hypereosinophilia is important in prognosis. We report a case of erythrodermic MF with hypereosinophilic syndrome in a 22-year-old female presenting with gradually progressive intractable erythroderma with intensely pruritic multiple papules, plaques, and nodules involving more than 90% of body surface area. Diagnosis was confirmed by histopathological examination and immunophenotyping from multiple skin biopsies.

Literature meta-analysis of zosteriform cutaneous metastases from melanoma and a clinico-histopathological report from India.

Cutaneous metastases in patients with malignant tumours are an important clue to tumour progression or even the first manifestation of malignancy. Among the various topographic patterns of cutaneous metastasis, the zosteriform pattern of metastasis is rare, and very few cases have been published. Various theories have been proposed for this zosteriform pattern of metastases, but none have been proved. We collected the available PubMed articles on zosteriform skin metastasis from cutaneous melanoma published since 1970 and reviewed the cases, including our own case. Melanoma presents with cutaneous metastasis in up to 44% of patients. Clinicians treating oncology patients should consider zosteriform skin metastasis in the differential diagnosis of zosteriform lesions to avoid inadequate diagnosis and management.

Role of fine needle aspiration cytology in diagnosing filarial arm cysts.

Filariasis is prevalent in tropical and subtropical areas and is endemic in regions of India. Lymphatic filariasis in India is caused mainly by two species of nematodes: Wuchereria bancrofti and Brugia malayi, which invade the human lymphatic system. We report two cases of superficial cystic lesions of the upper limb revealed on fine needle aspiration (FNA) to be clinically unsuspected filariasis. Despite similar aetiologies, both cases revealed variations in aspirate nature, smear morphology and peripheral blood findings. FNA provides definitive diagnosis and is an important tool for diagnosing soft tissue swellings owing to filariasis.

KIT proto-oncogene exon 8 deletions at codon 419 are highly frequent in acute myeloid leukaemia with inv(16) in Indian population.

The KIT gene is a receptor tyrosine kinase class III expressed by early hematopoietic progenitor cells and plays a significant role in hematopoietic stem cell proliferation, differentiation and survival which is considered to be a remarkable feature in the course of growth of acute myeloid leukaemia (AML). Owing to insufficient study of mutations in the KIT gene, the diagnosis and rate of recurrence of these mutations with divergent subtypes in AML cases in India is of concern. In order to find out the frequency of mutations of KIT gene exon 8 in 109 AML cases, we have performed polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by DNA sequencing and have identified 24 mutations in exon 8 in 13 cases, including deletions at codon 418 (n = 3), 419 (n = 11) and 420 (n = 5) as well as point mutations at codon 417 (n = 1) and 421 (n = 4). In eleven AML cases, exon 8 deletion and point mutations involved the loss at codon Asp419 immoderately conserved cross species placed in the receptor extracellular domain. Frequency elevation of the KIT proto-oncogene exon 8 deletion and point mutations in AML cases allude a crucial function for this region of the receptor extracellular domain. Thus, we report the incidence of acquired mutations in exon 8, with consistent loss at codon Asp419, in 10.09 % of AML cases in a selected Indian population.

Solitary cylindroma with malignant transformation.

A 59-year-old woman presented with a history of rapidly progressive recurrent tumor of 6.5 cm diameter of the scalp. Histopathological examination revealed a case of malignant cylindroma. There has been no recurrence or metastases and the patient is disease free at the end of 15 months postoperatively. Malignant transformation occurs less often in solitary form of cylindroma, but once transformed, tumors behave aggressively with extensive local infiltrative growth or metastases. The case is reported to document a rare case of malignant cylindroma arising in a patient with solitary cylindroma on the parieto-temporal region.

Comparative evaluation of the modified Scarff-Bloom-Richardson grading system on breast carcinoma aspirates and histopathology.

BACKGROUND: Fine needle aspiration (FNA) is a quick, minimally invasive procedure for evaluation of breast tumors. The Scarff-Bloom-Richardson (SBR) grade on histological sections is a well-established tool to guide selection of adjuvant systemic therapy. Grade evaluation is possible on cytology smears to avoid and minimize the morbidity associated with overtreatment of lower grade tumors. AIM: The aim was to test the hypothesis whether breast FNA from the peripheral portion of the lesion is representative of Scarff-Bloom-Richardson grade on histopathology as compared to FNA from the central portion. MATERIALS AND METHODS: Fine-needle aspirates and subsequent tissue specimens from 45 women with ductal carcinoma (not otherwise specified) were studied. FNAs were performed under ultrasound guidance from the central as well as the peripheral third of the lesion for each case avoiding areas of necrosis/calcification. The SBR grading was compared on alcohol fixed aspirates and tissue sections for each case. RESULTS: Comparative analysis of SBR grade on aspirates from the peripheral portion and histopathology by the Pearson chi-square test (χ(2) =78.00) showed that it was statistically significant (P<0.001) with 93% concordance. Lower mitotic score on aspirates from the peripheral portion was observed in only 4 out of 45 (9%) cases. The results of the Pearson chi-square test (χ(2) = 75.824) with statistically significant (P=0.000). CONCLUSION: This prospective study shows that FNA smears from the peripheral portion of the lesion are representative of the grading performed on the corresponding histopathological sections. It is possible to score and grade by SBR system on FNA smears.

Identification of the c-kit gene mutations in biopsy tissues of mammary gland carcinoma tumor.

C-kit gene is a transmembrane tyrosine kinase that acts as type III receptor for mast cell growth factor and cellular migration, proliferation, survival of melanoblasts, haematopoietic progenitors and primordial germ cells. Apart from the scant information about the pathologies associated with loss-of-function mutations, few reports have proposed role of the c-kit gene in case of carcinogenesis. Apparently, in breast cancer the involvement of c-kit gene mutations has been considered as a rare phenomenon. Thus, we designed our study with aim to investigate the c-kit gene mutation in breast cancer, and their correlation with clinico-pathological findings. We performed mutational analysis of the c-kit gene in 58 cases of malignant breast cancer. With the aim to ascertain the variety of mutations at exon 8, 9, 11, 13, 15 and 17 of c-kit gene in breast cancer, we have done PCR-SSCP followed by DNA sequencing. In breast cancer the c-kit gene mutation rates were 3.44% (02/58) in exon 8, 5.17% (3/58) in exon 9, 5.17% (3/58) in exon 11, 3.44% (2/580 in exon 13, 3.44% (2/58) in exon 15 and 5.17% (3/58) in exon 17, respectively. The overall c-kit mutation frequency in exons 8, 9, 11, 13, 15 and 17 was determined to be 25.86% (15/58). Our study indicates to specify the role of c-kit proto-oncogene mutation in breast cancer. The result signifies that c-kit gene plays a poor role in prognosis of ductal and lobular carcinoma.

Coexistence of leukemic infiltration and extramedullary hematopoeisis in a lymph node: A cytological diagnosis.

Extramedullary hematopoeisis (EMH) occurs when function of the bone marrow is insufficient or destroyed. We report a case of lymph nodal mass in a young patient, diagnosed on fine needle aspiration cytology (FNAC) as infiltration by leukemia along with features of EMH. FNA smears from axillary lymph node revealed lymphoblasts with hand mirror cell and teat cell morphology. Also seen were occasional megakaryocytes and metamyelocytes.

Cell Cannibalism: A cytological study in effusion samples.

BACKGROUND: Cytological examination of effusion fluid is a relatively easy and quick method for the diagnosis of primary or secondary malignancy. AIMS: To analyze the cytological significance of cell cannibalism in malignant effusion samples. MATERIALS AND METHODS: A retrospective review of 100 cases of malignant effusion was done. These 100 cases included 50 cases of contiguous, local spread to pleural/ascitic fluid. The remaining 50 cases were of disseminated malignancy. Effusions due to hematolymphoid malignancies were excluded. Smears from these cases were assessed for the presence of cell cannibalism, tumor cell within a tumor cell. RESULTS: The cannibalistic cells were more common in effusions with disseminated malignancy (nine out of 50 cases i.e. 18%) compared with cases of contiguous, local spread (two out of 50 cases i.e. 4%). Chi square test showed this difference to be statistically significant (x(2) 5.005, P=0.025). The majority of the cases were of carcinoma lung (6/11). Cytomorphologically, histiocytes displaying phagocytosis can simulate tumor cells and need to be distinguished. CONCLUSIONS: Presence of cell cannibalism in malignant effusions is more often an indicator of disseminated malignancy with secondaries and higher tumor stage. Furthermore, cannibalism may provide a reliable predictor of progression of tumor from primary to the metastatic site.