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Sertoli-Leydig cell tumors (SLCTs) of the ovary with mesenchymal heterologous elements are uncommon. Only few such cases have been documented, showing presence of only mesenchymal heterologous elements at the metastatic site. We report an unusual case in a young girl who presented with an omental mass that was consistent with histopathological features of a high-grade sarcoma, with prominent rhabdomyoblastic differentiation of the embryonal type. The sections from her ovarian mass for which she was operated a year back displayed features of a poorly differentiated SLCT with heterologous elements, including focal rhabdomyoblastic differentiation. This is one of the rare cases, to the best of our knowledge, where only rhabomyosarcomatous elements were identified at the metastatic site, mimicking a primary abdominal rhabdomyosarcoma, in a case of an ovarian SLCT. Further, this case reinforces the presence of rhabdomyosarcomatous elements in an ovarian SLCT to be associated with an aggressive disease course.

This study was carried out to observe the trend in hormone receptors over the last 8 years in a tertiary cancer center in India. A total of 11,780 tumors analyzed for hormone receptors over the last 7 years were compared with the results of hormone receptor expression in a prior published study on 798 cases of breast cancer from the same institute. The patient′s ages ranged from 18 to 102 years, Sixty percent of the patients were in the age group of 31-50 years. Seventy percent of the tumors were grade III tumors. The percentage of hormone receptor expression in breast cancer in the last 8 years varied from 52 to 57%. The overall receptor expression in the last 8 years shifted within a 5% range, confirming that the hormone receptor expression in Indian patients with breast cancer is low. However, there was redistribution within the pattern of estrogen receptor (ER) and progesterone receptor (PR) expression among tumors showing hormone receptor expression. Breast cancers showing only PR expression reduced dramatically from 21% in the year 1999 to in the year 2006, with a parallel increase in breast cancers showing combined ER and PR positivity (from 25 to 41.8%) and only ER expression (from 7.4 to 10.6%). The hormone receptor expression in breast cancers in India is and continues to be low but the high incidence of only PR-positive tumors in our population reported earlier was misrepresented.

Synovial sarcoma is a well defined morphologic entity extensively researched in literature. Synovial sarcoma displays a wide spectrum of clinical presentations and histologic appearances that may give rise to diagnostic dilemmas. One such unusual site in the head and neck area is the tongue. We report a case of monophasic synovial sarcoma of the tongue in a 22-year-old male. Microscopically, this tumor mimicked a poorly differentiated carcinoma which is more common at this site though the patient was young for this type of tumor. On immunohistochemistry, neoplastic cells were positive for cytokeratin, vimentin, calponin, CD99 and bcl2. Molecular studies - viz. reverse transcriptase polymerase chain reaction revealed a SYT-SSX translocation clinching the diagnosis. This paper highlights the immunohistochemistry profile and SYT-SSX translocation which helped arrive at an accurate diagnosis only because the index of suspicion for a monophasic synovial sarcoma is high.

Byline: R. Chinoy Like two buds I appear at puberty, When my ductules start branching like filigree, With maddening haste they like roots ramify To form perfect lobules that just [...]

Abstract The advent of mammography and increased awareness about breast cancer has resulted in the detection of smaller tumours. The majority of these small tumours would not have had metastasized [...]

Byline: P. Karve, N. Jambhekar, S. Desai, R. Chinoy Context: Frozen section is an invaluable intra-operative tool for evaluation of breast lumps. Aims: The aim of this study was to [...]

The most common tumors which metastatise to kidney are lymphoma, leukemia, and lungs. Metastatic tumors of the kidney are usually small, asymptomatic and occasionally cause flank pain and hematuria. Distinction [...]

The distinction between metastasis from a colorectal adenocarcinoma into the ovary and an ovarian adenocarcinoma is vital, but challenging at times, due to overlapping morphological features. Similarly, a distinction between an ovarian metastasis into the colorectum and a colorectal adenocarcinoma, although rare; is important and can be daunting. We report an analysis of 20 cases of ovarian involvement by metastatic colorectal adenocarcinomas and colorectal involvement by metastatic ovarian adenocarcinomas, including the value of differential expression of cytokeratins 7 & 20 by immunohistochemistry (IHC), in these cases. Nine cases (45%) were identified as colorectal adenocarcinomas metastatic to the ovary. On biopsy, all these cases showed a 'garlandlike' tumor necrosis, with desmoplasia and predominantly exhibited a tubuloalveolar pattern (67% cases). On IHC, all 8 of 9 such cases, where staining for cytokeratin 20 was performed, displayed strong positivity and 7 cases, where staining for carcinoembryogenic antigen (CEA) was performed, revealed positivity for this marker (100%). Other 11 cases (55%) were ovarian adenocarcinomas, metastatic to the colorectum. These showed metachronous presentations, with the ovarian tumor preceding the colorectal tumor deposits. Morphologically, psammomatous calcification was noted in 73% of these cases, whereas 'garland-like' necrosis was absent in all. The chief morphological subtype was serous papillary cystadenocarcinoma (55% cases). On IHC, CK7 and CA 125 were positive in all 6 of 11 such cases, whereas CK 20 was negative in all these cases. In cases of complex presentations like an ovarian involvement by a metastatic colorectal adenocarcinoma and vice-versa, certain clinicopathological features are useful. Differential expression of CK 7 and CK20 is vital in resolving these dilemmas. CK20 positivity and CK7 negativity is associated with a colorectal adenocarcinoma. Markers like CEA and CA-125 have an added value. [ABSTRACT FROM AUTHOR]

There is insurgence of literature evaluating prognostic and predictive factors in breast carcinomas treated with chemotherapy, with a parallel need to develop guidelines for the pathologist interpreting such excisions. Prechemotherapy gun biopsy and postchemotherapy excision specimens from 78 women with locally advanced breast cancer were analyzed for histological changes in the tumor, changes in the tumor grade, hormone receptors, cerb2, and bcl2 and their impact on disease-free survival (DFS). An unusually prominent granulomatous response to tumor was seen in three cases. The tumor grade changed in five patients, estrogen receptor (ER) expression was altered in 10 cases, progesterone receptor detection changed in 16 cases, cerb2 in one case and bcl2 in 16 cases. Fixation of the gun biopsy in Bouin's fluid and severe damage of nuclei after chemotherapy were the reasons for shift in the expression of hormone receptors. A low-grade tumor was associated with better response to chemotherapy. In the Kaplan-Meier analysis the ER expression and a low-grade tumor (grade I and II) significantly affected DFS. None of the factors evaluated impacted the overall survival of patients. To conclude there is a change in the tumor grade, bcl2, cerb2 and hormone receptors after chemotherapy. A pathologist interpreting specimens of breast cancer after chemotherapy must always record the postchemotherapy grade as it is an indicator of better response to chemotherapy and survival. [ABSTRACT FROM AUTHOR]

Background: Fine needle aspiration cytology (FNAC) forms one of the first diagnostic tools in the evaluation of tumors. Its role in diagnosing soft tissue tumors (STT) has been fairly documented, as well as debated. Present study was aimed at evaluating its scope in diagnosing 127 cases of soft tissue tumors. Methods: Conventional Pap and MGG staining was available in all the cases. Immunocytochemistry (ICC) was performed in 15 cases. Histopathological details were available in 115 cases. Results: 50% cases were referred for a primary diagnosis, while 26.8% & 22.8% cases were evaluated for recurrent and metastatic lesions, respectively. Extremities were the commonest sites. On FNAC, 101 cases (79.5%) were labeled as malignant, whereas 10 cases (7.9%) were labeled as benign. The remaining 16 cases (11%) were not categorized and were labeled as 'unsure/not specified'. Histopathological confirmation in 115 cases, gave a diagnostic accuracy of 98%, with a positive predictive value of 98% in malignant cases and a negative predictive value of 100% in benign cases. Two cases were false positive. Among the various cytological categories, 60 cases (47.2%) were of spindle cell type, followed by 32 (25.2%) of round cell type and 14 cases (11%) of lipomatous type. Other 12 cases (9.4%) were of pleomorphic type; 7 (5.5%) cases of epithelioid type and remaining 2 cases were of myxoid type. All the round cell, pleomorphic and myxoid type of tumors were sarcomas, whereas 73.3% cases of spindle cell type were labeled as 'malignant'. Exact cytological sub typing was offered in 58 cases, with rhabdomyosarcoma (RMS) as the most frequently sub typed tumor. The two false positive malignant cases were of fibromatosis and a pigmented schwannoma, on biopsy. Out of 28 metastatic lesions, lymph nodes were the commonest site for metastasis, with epithelioid tumors that formed highest percentage of metastatic cases. Conclusion: FNAC is fairly specific and sensitive in STT diagnoses for primary, recurrent and metastatic lesions. The cytological types, especially round cell and pleomorphic sarcomas, can be quickly identified. Clinicopathological correlation with ICC as an adjunct, are valuable in exact sub typing. [ABSTRACT FROM AUTHOR]

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor and often poses a diagnostic and therapeutic challenge to the involved clinicians. We report a case of epithelioid trophoblastic tumor in a young woman which involved the uterus, parametrium and the right ovary. Misdiagnosis as a choriocarcinoma led to improper treatment and progressive disease. Microscopically it revealed a relatively monotonous population of epithelioid cells arranged in nests with hyaline-like matrix surrounding the tumor cells. Differential diagnosis between placental site trophoblastic tumor and carcinoma was ruled out based on histology and immunohistochemistry. The patient developed lung and brain metastasis after 10 months and is alive with disease 1½ years thereafter and is taking palliative chemotherapy. The patient had β-HCG level of 85.1 mIU/mL at the time of diagnosis; but just before metastasis, the levels rose. Awareness of the histological features of ETT is essential to avoid misdiagnosis, as it represents a tumor which is primarily treated by surgery rather than with chemotherapy.

Abstract The distinction between metastasis from a colorectal adenocarcinoma into the ovary and an ovarian adenocarcinoma is vital, but challenging at times, due to overlapping morphological features. Similarly, a distinction between an ovarian metastasis into the colorectum and a colorectal adenocarcinoma, although rare; is important and can be daunting. We report an analysis of 20 cases of ovarian involvement by metastatic colorectal adenocarcinomas and colorectal involvement by metastatic ovarian adenocarcinomas, including the value of differential expression of cytokeratins 7 & 20 by immunohistochemistry (IHC), in these cases. Nine cases (45%) were identified as colorectal adenocarcinomas metastatic to the ovary. On biopsy, all these cases showed a 'garland-like' tumor necrosis, with desmoplasia and predominantly exhibited a tubuloalveolar pattern (67% cases). On IHC, all 8 of 9 such cases, where staining for cytokeratin 20 was performed, displayed strong positivity and 7 cases, where staining for carcinoembryogenic antigen (CEA) was performed, revealed positivity for this marker (100%). Other 11 cases (55%) were ovarian adenocarcinomas, metastatic to the colorectum. These showed metachronous presentations, with the ovarian tumor preceding the colorectal tumor deposits. Morphologically, psammomatous calcification was noted in 73% of these cases, whereas 'garland-like' necrosis was absent in all. The chief morphological subtype was serous papillary cystadenocarcinoma (55% cases). On IHC, CK7 and CA 125 were positive in all 6 of 11 such cases, whereas CK 20 was negative in all these cases. In cases of complex presentations like an ovarian involvement by a metastatic colorectal adenocarcinoma and vice-versa, certain clinicopathological features are useful. Differential expression of CK 7 and CK20 is vital in resolving these dilemmas. CK20 positivity and CK7 negativity is associated with a colorectal adenocarcinoma. Markers like CEA and CA-125 have an added value.

Abstract Background Epithelioid sarcoma (ES) is an uncommon soft tissue sarcoma. Lately, subtypes of ES, including proximal-type ES have been recognized, with relatively few reports on such cases. Case presentation A 47-year-old male presented with a perineal soft tissue mass that was excised elsewhere and the biopsy was submitted for a review diagnosis. On histology, a multi nodular tumor was seen comprising sheets of oval to polygonal cells with moderate amount of cytoplasm. Interspersed were larger, rhabdoid cells with abundant eosinophilic cytoplasm and prominent nucleoli. Focal necrosis was noted. A wide panel of immunohistochemical (IHC) markers was performed to rule out a range of differential diagnoses, including a poorly differentiated carcinoma, a melanoma and a variety of sarcomas with epithelioid differentiation. On IHC, the tumor cells showed a polyphenotypic expression, including positivity for epithelial markers i.e cytokeratin (CK), CK7, EMA and mesenchymal markers like vimentin and CD 34. Desmin was focally positive. CK20, CEA, S-100, HMB-45, SMA, LCA and CD31 were negative. A diagnosis of a proximal-type ES was formed. Six moths later, despite adjuvant chemo and radiotherapy (CT and RT), the patient continued to have the lesion and was referred again. In addition to the earlier histological features, sections from the persistent tumor mass showed an increased number of larger cells along with multinucleated tumor giant cells. Conclusion The value of identifying this uncommon tumor from a list of differential diagnoses is in view of its aggressive behavior, as seen in our case. A wide excision with clear margins is imperative with options of post-operative CT/RT in individual cases during a close follow-up.

Abstract Background Fibromatosis-like metaplastic carcinoma is a newly described metaplastic breast tumor, literature on which is still evolving. Case presentation A 77-year-old lady presented with a 2 × 2 cm mass with irregular margins in the upper and outer quadrant of left breast. Fine needle aspiration cytology (FNAC) from the lump was inconclusive. A lumpectomy was performed and sent for frozen section, which revealed presence of spindle cells showing mild atypia in a sclerotic stroma. The tumor cells revealed prominent infiltration into the adjacent fat. A differential diagnosis of a low-grade sarcoma vs. a metaplastic carcinoma, favoring the former, was offered. Final histology sections revealed an infiltrating tumor with predominant spindle cells in a collagenous background, simulating a fibromatosis. Adjacent to the tumor were foci of benign ductal hyperplasia and a micropapilloma. Immunohistochemistry (IHC) showed diffuse co-expression of epithelial markers i.e. cytokeratins (CK, HMWCK, CK7) and EMA along with a mesenchymal marker i.e. vimentin in the tumor cells. Myoepithelial markers (SMA and p63) showed focal positivity. A diagnosis of a low-grade fibromatosis-like carcinoma breast associated with a micropapilloma was formed. Conclusion Fibromatosis-like carcinoma is a rare form of a metaplastic breast tumor. This diagnosis requires an index of suspicion while dealing with spindle cell breast tumors. The importance of making this diagnosis to facilitate an intra operative surgical planning is marred by diagnostic difficulties. In such cases, IHC is imperative in forming an objective diagnosis.

Introduction: Expression of cytokeratin intermediate filaments by a tumour was traditionally considered as proof of epithelial origin. Increasing documentation of cytokeratin expression within tissues and neoplasms of mesenchymal origin has challenged this notion. Aims: To study the pattern of cytokeratins expression in 375 soft tissue sarcomas. Materials and Methods: A retrospective study of 375 soft tissue sarcomas at various anatomical sites which were reported between 2003-2006 was done. All cases wherein cytokeratin was one of the antibodies in the IHC panel were analysed and correlated with histologic subtype. Results: CK immunoreactivity was observed in 69 of 375 soft tissue sarcomas (18.4%).The various subtypes were: synovial sarcoma (30/108), epithelioid sarcoma (15/28), pleomorphic sarcoma (3/19), leiomyosarcoma (2/17), PNET (2/25), DSRCT (5/8), extra renal rhabdoid tumour (2/2), sarcoma with epithelioid morphology (5/20), alveolar soft part sarcoma (1/4), chordoma (1/1), mesothelioma (1/4), myofibroblastic sarcoma (1/2), benign smooth muscle neoplasm of muscle origin (1/1). None of the cases classified as high grade sarcoma of uncertain histogenesis (50), MPNST (18), liposarcoma (6), MFH (7), melanoma/ clear cell sarcoma of soft part (9), epithelioid MPNST (10) and epithelioid angiosarcoma (7) revealed CK positivity. The immunoexpression was extensive and intense in biphasic synovial sarcomas and epithelioid sarcomas, whereas it was focal and weak in the remaining subtypes. Tumours with epithelioid morphology showed maximum immunoreactivity on routine histology. Conclusion: The presence of CK expression in 18% of all sarcomas and in 41.6% of sarcomas with epithelioid morphology highlights the fact that aberrant expression of CK intermediate filaments is not infrequent in sarcomas. Cytokeratins are often used as a marker to support a diagnosis of carcinoma over a sarcoma. Hence these observations by a trained surgical pathologist are vital for interpreting IHC results. [ABSTRACT FROM AUTHOR]

Background: Pathological features of primary ovarian epithelial carcinomas overlap with metastatic colorectal adenocarcinomas. Exact primary diagnosis becomes challenging in cases of ovarian involvement by colorectal adenocarcinomas and vice versa. Lately, differential expression of cytokeratins (CK7 and CK20) has emerged in resolving diagnostic dilemmas relating to exact primary sites in such presentations. Aims: We sought to identify differential expression of CK 7 and CK20 in 16 cases of synchronous or metachronous adenocarcinomas involving ovary and colorectum, accrued over a period of 5 years. Materials and Methods: Conventional Hematoxylin and Eosin stained micro sections were supplemented with immunohistochemical (IHC) markers like CK7, CK20, CA125 and CEA, as and when required. Complete clinicopathological details, including serum tumor marker (TM) levels for CA125 and CEA were noted. Results: Out of 16 cases, 9 (56.25%) were of ovarian origin and 7 (43.75%) of colorectal origin. Six cases showed synchronous involvement. Morphologically, 6 ovarian cases included 5 papillary serous cystadenocarcinomas and 1 of endometrioid type, while 7 colorectal adenocarcinomas included 4 tubuloglandular, 2 mucinous and 1 case of signet-ring cell type. Remaining 3 cases were classified as poorly differentiated adenocarcinomas (NOS type). IHC was performed in 12 (75%) cases. CK7+/CK20-vity was noted in 6 cases, confirming an ovarian origin. CK20+/CK7-vity was seen in 3 cases, confirming a colorectal origin. Strong CK20 +/Weak CK7+vity was seen in 3 cases. These cases further showed CA125 negativity and CEA positivity, along with high serum CEA levels, as corroborative evidences for a colorectal primary. Histomorphologically, all cases of colorectal adenocarcinomas exhibited .garland-like. necrosis. Lymphovascular emboli were noted in 57% cases of colorectal metastasis to ovary and in 33% cases of ovarian metastasis to colorectum. Psammomatous calcification was seen in all 5 cases of papillary serous cystadenocarcinomas, 1 case of poorly differentiated ovarian adenocarcinoma and 1 case of colorectal adenocarcinoma. Conclusions: Differential CK7 and CK20 expression is helpful in identifying primary tumor in cases of ovarian involvement by colorectal adenocarcinomas and vice versa. Inclusion of CA125 and CEA in the IHC panel, along with their TM levels, has added value. Clinicopathological correlation is necessary in such cases before treatment decisions are undertaken. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Naked eye visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugol's iodine (VILI), cytology and human papillomavirus (HPV) testing were evaluated as screening methods for the detection of high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in a cross-sectional study in Mumbai, India. METHODS: Cytology, HPV testing, VIA, VIAM and VILI were carried out concurrently for 4039 women aged 30-65 years. All women were investigated with colposcopy and biopsies were taken from 939 women who had colposcopic abnormalities. The reference standard for final disease status was histology or negative colposcopy. The presence of HSIL was confirmed in 57 women (1.4%). The test characteristics for each method were calculated using standard formulae. RESULTS: The sensitivities of cytology, HPV testing, VIA, VIAM and VILI were 57.4%, 62.0%, 59.7%, 64.9%, and 75.4%, respectively (differences were not statistically significant). The specificities were 98.6%, 93.5%, 88.4%, 86.3%, and 84.3%, respectively. Adding a visual test to cytology or HPV testing in parallel combination resulted in a substantial increase in sensitivity, with a moderate decrease in specificity. The parallel combination of VILI and HPV testing resulted in a sensitivity of 92.0% and a specificity of 79.9%. CONCLUSION: As a single test, cytology had the best balance of sensitivity and specificity. Visual tests are promising in low-resource settings, such as India. The use of both VIA and VILI may be considered where good quality cytology or HPV testing are not feasible. The sensitivity of cytology and HPV testing increased significantly when combined with VIA or VILI. Copyright © 2005 World Health Organization [ABSTRACT FROM AUTHOR]

A 68-year-old male presents with generalized lymphadenopathy and fever of short duration. Axillary lymph node excision was performed and was sent for histopathological evaluation. Microscopic evaluation of the submitted lymph node revealed diffuse proliferation of intermediate-sized atypical lymphoid cells with round nuclei, irregular membranes, finely dispersed chromatin, and inconspicuous nucleoli. Mitotic figures were frequently seen. Immunohistochemical evaluation revealed diffuse expression of CD20, CD5, CD10, B-cell lymphoma 2 (Bcl2), and B-cell lymphoma 6 (Bcl6). Atypical lymphoid cells were negative for cyclin D1; however, showed diffuse and strong nuclear expression of SOX11. MIB1 proliferation index was high (Ki67: 90%-95%). Based on morphological features and immunohistochemical findings a diagnosis of "cyclin D1 negative aggressive blastoid variant of mantle cell lymphoma (MCL)" was offered. The classic morphology of MCL is seen in 90% of cases, while the remaining (∼10%) are considered as variants. A blastoid variant is an aggressive subtype that can lack expression of CD5 as well as cyclin D1, but instead expresses CD10, Bcl6, and CD23. SOX11 expression is seen in 90% cases of MCL and in almost 100% cases of cyclin D1 negative MCL. The current case highlights the unusual morphologic and aggressive variant of MCL and a significant role of SOX11 in its diagnosis.

The high burden of cervical cancer and inadequate/suboptimal cytology screening in developing countries led to the evaluation of visual screening tests, like visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). We describe the performance of VIA, VILI and cytology, carried out in a multinational project called "Screening Technologies to Advance Rapid Testing" in 5,519 women aged 30-49 years, in detecting cervical intraepithelial neoplasia (CIN). VIA, VILI and cytology were positive in 16.9%, 15.6% and 6.1% women, respectively. We found 57 cases of CIN2, 55 of CIN3 and 12 of cervical cancer; 90% of CIN3 and 43% CIN2 cases were positive for p16 overexpression and high-risk HPV infection, indicating a high validity of histological diagnosis. The sensitivity of VIA, VILI and cytology to detect high-grade CIN were 64.5%, 64.5% and 67.7%, respectively; specificities were 84.2%, 85.5% and 95.4%. A high proportion of p16 positive CIN 3 (93.8%) and 2 (76.9%) were positive on cytology compared with visual tests (68.8% and 53.8%, respectively) indicating a higher sensitivity of cytology to detect p16 positive high-grade CIN. However, the immediate availability of the results from the visual tests permits diagnosis and/or treatment to be performed in the same sitting, which can potentially reduce loss to follow-up when women must be recalled following positive cytology. Organizing visual screening services in low-resource countries may facilitate the gradual building of an infrastructure committed to screening allowing the eventual introduction of more sensitive, highly objective, reproducible and affordable human papillomavirus screening tests in future., (Copyright © 2012 UICC.)

Background & Objectives: Determination of HER2 status in breast cancer has become important to identify potential candidates for anti-HER2 therapy. In this study we compared fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for the determination of HER2 status in breast cancer patients referred to a tertiary care referral centre., Methods: A total of 200 cases of invasive breast cancer were evaluated for HER2 status using IHC and FISH and results were compared., Results: The IHC 3+ (93.9%) and IHC negative (85.9%) cases showed good concordance with the corresponding FISH results; while 66.6 per cent of IHC 2+ cases showed gene amplification by FISH. In addition, hormone receptor expression and HER2 gene status showed a statistically significant inverse association (P<0.05)., Interpretation & Conclusion: These findings reaffirm IHC as a prudent first-step to screen tissue samples for HER2 status and to determine suitability for technically demanding FISH test and the dual coloured FISH as a gold standard for determination of HER2/neu status in IHC equivocal cases of breast carcinoma.

The histological criteria of uterine cervix lesions are well known. However, there is a poor diagnostic reproducibility especially concerning low-grade precancerous lesions. Therefore, the aim of our study was to evaluate the utility of p16INK4A overexpression as a surrogate biomarker of precancerous lesions of the uterine cervix. A retrospective study was carried out by the International Center for Research on Cancer, Lyon, on 79 uterine cervix lesions. Specimens included 4 normal tissue samples, 24 benign lesions, 9 low-grade precancerous lesions (CIN1), 40 high-grade precancerous lesions (CIN2-3) and 2 squamous cell carcinomas. Immunohistochemistry was used to find p16INK4A expression. HPV infection was detected by HPV testing. No p16INK4A expression was detected in normal tissues and benign lesions of the uterine cervix. p16INK4A immunolabeling was weak in CIN1 cases (77.8%). Strong and diffuse p16INK4A expression was detected among all precancerous lesions (CIN2-3) and squamous cell carcinomas. p16INK4A overexpression was associated to the CIN grade (p<0.0001) and high-risk HPV infection (p<0.0001). In conclusion, p16INK4A overexpression should be regarded as a surrogate biomarker of precancerous lesions of the uterine cervix. p16INK4A overexpression is useful in reducing the variability during evaluation of suspicious biopsies of the uterine cervix.

Background: In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India., Methods: In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment., Results: In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women., Conclusions: In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer., (2009 Massachusetts Medical Society)

Infiltrating micropapillary carcinomas (IMPC) of breast are highly angioinvasive tumors with poor prognosis. This study is based on the observation that a similar micropapillary pattern is also observed in mucinous carcinomas of breast. About 102 mucinous carcinomas were evaluated for the presence and impact of this micropapillary pattern on the clinical behavior. Of these, 68 were mucinous carcinomas with a micropapillary pattern (MUMPC), 20 had MUMPC mixed with an infiltrating duct carcinoma component, two were solid variants of papillary carcinoma with mucin (SVPCMU), five had collision of the MUMPC and SVPCMU patterns and seven were mucinous carcinomas with signet ring cells (MUS). The factors negatively affecting overall survival (OAS) and disease-free survival (DFS) included the histological type of mucinous carcinoma, nodal metastases, an irregular tumor border, <50% mucin and an IMPC type of local recurrence or metastases. In the multivariate analysis, the histologic type of mucinous carcinoma and an irregular tumor border were most significant for OAS and DFS. Thus, 86% of mucinous carcinomas in this study were mucinous variants of the angioinvasive infiltrating micropapillary carcinomas. These tumors can produce IMPC type of metastases and thus should be treated aggressively.

Objective: To evaluate accuracy and role of immunocytochemistry (ICC) in cytologic diagnosis of pediatric renal tumors., Study Design: Fine needle aspirates from 75 cases of pediatric renal tumors were studied. Radiologic-guided aspirations were performed, with 6-7 smears stained with Papanicolaou and Giemsa stains. Smears were screened without the knowledge of final histologic diagnosis. Subsequently, clinical details, final histology and diagnosis rendered by the original cytologist were noted to judge accuracy of diagnosis by a sensitized cytologist. Five neuroblastomas that entered close differentials for Wilms tumor were also evaluated. ICC studies were also performed after staining., Results: Of 58 Wilms tumors, 5 were misdiagnosed; 3 renal rhabdoid tumors and 1 clear cell sarcoma were missed on cytology. Non-Hodgkin's lymphomas presenting as renal masses were accurately diagnosed on cytology, but primitive neuroectodermal tumors (n = 3) and renal cell carcinomas (n = 2) were not accurately diagnosed. Accuracy rate improved from 65% to 92% on review by a cytologist aware of cytologic features of pediatric renal tumors., Conclusion: A good accuracy rate of diagnosis of pediatric renal tumors can be achieved by priming pathologists to typical features of tumors. Immunocytochemistry plays a supportive role in cases with atypical morphology or unusual presentations.

Solitary fibrous tumour (SFT) is a rare spindle cell neoplasm arising at pleural and extrapleural sites. Five cases of SFT diagnosed at our institution over a five year period were reviewed. Haematoxylin and eosin stained histological sections, immuno-histochemical markers including CD34 and electron microscopy were the different methods used to study these tumours. Three histological features were consistently observed in all the tumours: the tumours were composed of short spindle cells separated by dense collagen bands and arranged in alternate hypocellular and hypercellular areas. CD34 positivity was seen in all the cases. SFT's have been reported to behave in an unpredictable fashion and hence prolonged follow up is essential. Histology, CD34 positivity and electron microscopy are useful tools in diagnosing SFT. While the pleural tumours can be diagnosed based on histology, this must be substantiated by ancillary techniques in case of extrapleural tumours.

Objective: To examine the observation that some mucinous carcinomas have a micropapillary pattern and are mucinous variants of the highly angioinvasive infiltrating micropapillary carcinomas (IMPC)., Study Design: We evaluated cytologic findings of 13 IMPC and 55 mucinous carcinomas for comparative features., Results: In mucinous carcinomas, 37 of 50 (74%) had a micropapillary pattern. This group included 27 cases with pure mucinous micropapillary morphology (MUMPC), 8 MUMPC associated with a ductal carcinoma of the IMPC type (MUIDC) and 2 cases of mixed mucinous carcinomas with an MUMPC and a solid variant ofpapillary carcinoma (SVPC) component. On cytology both IMPC and mucinous carcinomas with micropapillary pattern demonstrated the micropapillary pattern, that is, angulated clusters or abortive papillae and ball-like clusters. However, the IMPC smears revealed numerous singly scattered tumor cells and larger fragments with shrub-like branching and the MUMPC had psammoma bodies. The mixed MUMPC and SVPC showed the classic cytologic features of MUMPC admixed with abundant singly dispersed tumor cells in the background representing the SVPC component., Conclusion: Although IMPC and the MUMPC share the micropapillary pattern on histologic examination, mucin alters the appearances in aspirates. Recognition of this morphologic spectrum will help in understanding the behavior of these tumors.

Objective: To standardize an inexpensive and rapid Papanicolaou staining technique with limited ethanol usage., Study Design: Smears from 200 patients were collected (2 per patient) and fixed in methanol. Half were subjected to conventional Papanicolaou and half to stain ing with rapid, economical, acetic acid Papanicolaou (REAP) stain. In REAP, pre-OG6 and post-OG6 and post-EA36 ethanol baths were replaced by 1% acetic acid and Scott's tap water with tap water. Hematoxylin was preheated to 60 degrees C. Final dehydration was with methanol. REAP smears were compared with Papanicolaou smears for optimal cytoplasmic and nuclear staining, stain preservation, cost and turnaround time., Results: With the REAP method, cytoplasmic and nuclear staining was optimal in 181 and 192 cases, respectively. The staining time was considerably reduced, to 3 minutes, and the cost per smear was reduced to one fourth. The staining quality remained good in all the smears for > 2 years., Conclusion: REAP is a rapid, cost-effective alternative to Papanicolaou stain. Though low stain penetration in large cell clusters is a limitation, final interpretation was not compromised.

Background: Primary angiosarcomas of breast are rare tumors, with a fatal outcome., Material and Methods: We studied histological prognostic factors and c-kit expression by immunohistochemistry (IHC) in 12 angiosarcomas accessioned at a cancer referral center in India., Results: All patients had primary angiosarcoma; no case of secondary angiosarcoma was accessioned during the study period. Median age of patients was 24.5 years. Nine patients had intermediate grade tumors, one a well differentiated tumor and three patients had high-grade tumors. Interesting cases encountered included an epithelioid angiosarcoma and an angiosarcoma arising on the background of a biphasic tumor. Eight patients had lumpectomy, four mastectomy and two patients were given radiotherapy. Of the nine patients (seven type I/II and two high grade) with follow up, eight patients developed disseminated metastases within a year of presentation. The patient with well-differentiated angiosarcoma also died of metastasis albeit after a longer time. On IHC c-kit staining was weakly seen in two cases., Conclusion: Primary angiosarcoma was fatal in young Indian women even in lower grade tumors. The low expression of c-kit on IHC suggests that targeting this protein for therapy may not be successful in treating these tumors., (Copyright (c) 2006 Wiley-Liss, Inc.)

A 26-year-old female with a tibial lesion diagnosed as an adamantinoma was treated with intra-lesional curettage, bone grafting and intra-medullary nailing. Six years post-surgery, she presented with an asymptomatic primary site but with a metastatic lesion in the mid-shaft of the ipsilateral femur and lung metastases. The femoral lesion was treated with wide excision and reconstructed with an allograft and plate fixation. Pulmonary metastatectomy was carried out for the lung lesions. A follow-up CT scan of the chest at 1 year after the surgery for the metastatic lesions revealed fresh unresectable bilateral metastases. Although cases of local recurrences and pulmonary metastases in adamantinoma are reported, this case is unusual in presenting without a local recurrence but with simultaneous skeletal and pulmonary metastases.

We analysed 46 telecytology cases sent from two rural hospitals about 500 km from a tertiary cancer centre. The cases were submitted for second opinion over a period of two years and evaluated using a static store and forward telecytology approach. A total of 715 digital images were studied (average 15 per case). Forty-one of the 46 cases (89%) were reported within 3 days and 54% of cases were reported within one working day. The aspiration smears and images were found to be of diagnosable quality in 89 and 93% of the cases, respectively. The diagnostic concordance was assessed by comparing the telecytology diagnosis, glass slide diagnosis and final histopathology diagnosis (when available). A clinically useful diagnosis was rendered in 91% cases with 74% complete concordance. Five out of 46 cases (11%) were deferred for glass slide review. Store and forward telecytology using the Internet is a rapid and effective method of providing expert diagnosis in cytology.

The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy/biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p = 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments., ((c) 2005 Wiley-Liss, Inc.)