Ranjan Basak

Synovial sarcoma of the kidney

The renal parenchyma is a rare site of origin for primary synovial sarcoma (SS). The present study describes the clinicopathologic, immunohistochemical, and molecular analysis of 7 cases of SS occurring in the kidney. There were 5 female and 2 male patients, with an age range of 15 to 46 years. They presented with solitary renal masses ranging in size from 10.0 cm to 17.0 cm in greatest dimension. Radical nephrectomy was performed in all cases. On gross examination, tumors were large, partially necrotic, and were seen to contain smooth-walled cysts in 4 cases. Histologically, the tumors were characterized by monomorphic spindle cells with indistinct cell borders arranged in intersecting nodular foci with hypocellular myxoid areas, together with a prominent hemangiopericytomatous pattern. The cysts were lined by hobnailed cells with eosinophilic cytoplasm. Immunohistochemically, BCL-2 was positive in all 6 cases in which it was performed, followed by vimentin (4/5 cases), MIC2 (CD99; 2/5 cases), calponin (2/2 cases), and epithelial membrane antigen (1/4 cases). Stains for cytokeratin and CD34 were consistently negative. Reverse transcription-polymerase chain reaction (RT-PCR) using RNA extracted from formalin-fixed paraffin-embedded tissues was carried out in 4 cases and SYT-SSX fusion gene transcript, which is the diagnostic hallmark of SS, was detected. Two patients developed pulmonary metastasis and died 6 and 12 months after diagnosis, respectively. This series of cases is distinct in terms of its morphological spectrum and confirmation by molecular technique.

Ewing sarcoma/primitive neuroectodermal tumor of the kidney: clinicopathologic analysis of 34 cases.

The present study describes the clinicopathologic analysis of 34 cases of Ewing sarcoma/primitive neuroectodermal tumor occurring in the kidney. The patients were 21 males and 13 females with an age range of 6 to 44 years. Clinically, patients presented with multiple symptoms including hematuria, pain, and/or lump in the abdomen. Nephrectomy was performed in most of the cases. Grossly, whole of the renal parenchyma was involved by a variegated tumor. Histologically, the tumor was composed of monomorphic, small, and round cells arranged in a variety of patterns. Rosettes, geographical areas of necrosis, and arborizing vascular pattern were the prominent histologic features. The nucleus was monomorphic and round. Anisonucleosis was also noted in some cases. The nucleus was mostly hyperchromatic. A mixture of hyperchromatic and powdery chromatin was noted in few cases. Immunohistochemically, MIC2 (CD99) was positive in 32 of 34 cases followed by neuron-specific enolase (9/12 cases), vimentin (8/14 cases), synaptophysin (1/8 cases), and S-100 protein (1/4 cases). Molecular analysis by reverse transcriptase-polymerase chain reaction that was carried out in 26 cases revealed presence of EWS-FLI-1 type 1 translocation in 12 cases, EWS-FLI-1 type 2 translocation in 10 cases, and both type 1 and type 2 EWS-FLI-1 translocation in 2 cases. Two cases did not demonstrate any translocation. Follow-up data were available for 17 of 34 cases. Local recurrence of the tumor was seen in 4 patients, and 10 patients were recorded to have distant metastasis in various organs, such as lung, bone, and lymph node, during the course of the disease.

Primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old woman: a case report

IntroductionPrimary Ewings sarcoma or primitive neuroectodermal tumor of the genital tract of women is uncommon. Rarer still is its occurrence in the vagina, with only five cases described so far. Out of these, only one case was confirmed using molecular analysis.Case presentationWe present an extremely rare case of Ewings sarcoma or primitive neuroectodermal tumor in a 17-year-old Indian girl. She presented with a vaginal mass that was initially diagnosed as a malignant round cell tumor. Immunohistochemistry showed diffuse positivity for vimentin, membranous positivity for MIC2, and positivity for BCL2 and FLI-1. On the other hand, she was negative for cytokeratin, epithelial membrane antigen, desmin, Myo D-1, myogenin and smooth muscle actin. A diagnosis of primitive neuroectodermal tumor was thus offered. Furthermore, a molecular analysis of our patient using reverse transcription-polymerase chain reaction technique showed positivity for t(11; 22) (q24; q12) (EWSR1-FLI1), thus confirming the diagnosis of a Ewings sarcoma/primitive neuroectodermal tumor. Our patient was offered chemotherapy on Institutional protocol EFT 2001.ConclusionThis is a rare case of primary vaginal Ewings sarcoma or primitive neuroectodermal tumor, which was confirmed with molecular analysis, in the youngest patient known so far. This study reinforces the value of integrating morphological features with membranous MIC2 positivity, along with application of molecular techniques in objective identification of an Ewings sarcoma or primitive neuroectodermal tumor at uncommon sites.

Desmoplastic Small Round Cell Tumor-Clinicopathological Spectrum, Including Unusual Features and Immunohistochemical Analysis of 45 Tumors Diagnosed at a Tertiary Cancer Referral Centre, with Molecular Results t(11; 22) (p13; q12) (EWS-WT1) in Select Cases

Desmoplastic small round cell tumor (DSRCT) is a distinct soft tissue tumor of uncertain histogenesis, mostly composed of small round cells; is characterized by polyphenotypic differentiation and a translocation t(11; 22)(p13; q13), resulting in formation of a specificEWS-WT1 fusion gene transcript [1]. This tumor was initially described by Sesterhenn et al. [2] as an undifferentiated malignant epithelial tumor involving serosal surfaces of scrotum and abdomen in young males. In 1989, Gerald and Rosai [3] published the first case that they designated as a desmoplastic small round cell tumor (DSRCT) with divergent differentiation. In the following year, Gonzalez-Crussi et al. [4] documented three additional cases of an intra-abdominal DSRCT. Subsequently, Gerald et al. [5] published the first large series of IADSRCT stating its predilection for adolescent males; an almost intra-abdominal location with rare secondary organ involvement and its classical histopathological features. Sawyer et al. [6] identified t (11; 22) (p13; q13) translocation for the first time in an IADSRCT. Ordonez et al. [7] identified a single case of ‘IADSRCT’ in the scrotum in their series of 22 cases. Thereafter, this tumor has been documented in form of series and case reports in intra and extra-abdominal sites like ovary, paratesticular region, pleura, soft tissues, including head and neck and finally recognized as a DSRCT [1, 8–16]. It is a highly malignant tumor that displays variable epithelial, mesenchymal and neural differentiation, demonstrated by immunohistochemical stains; mostly involves abdominal sites of young male patients, spreads along serosal surfaces; has an aggressive clinical course with frequent recurrences, rarely metastasis and is refractory to conventional, individual treatment modalities like surgery, chemotherapy (CT) and radiotherapy (RT). Apart from its classical histopathological features, including small round cells embedded in a desmoplastic stroma, a spectrum of features has been described, including tumors B. Rekhi (*) : S. Ahmed : S. S. Desai :M. Ramadwar : S. B. Desai :N. A. Jambhekar Department of Pathology, Tata Memorial Hospital, Dr E.B. Road, Parel, Mumbai, India 400012 e-mail: rekhi.bharat@gmail.com

Primary primitive neuroectodermal tumor of the uterus: A case report with an unusual molecular pathology finding

1. Kumar S, Kumar D, Cowan DF. Transitional cell carcinoma with rhabdoid features. Am J Surg Pathol 1992;16:515-21. 2. Parwani AV, Herawi M, Volmar K, Tsay SH, Epstein JI. Urothelial carcinoma with rhabdoid features: Report of 6 cases. Hum Pathol 2006;37:168-72. 3. Weeks DA, Beckwith JB, Mierau GW, Zuppan CW. Renal neoplasms mimicking rhabdoid tumor of kidney. A report from the National Wilms’ tumor study Pathology Center. Am J Surg Pathol 1991;15: 1042-54. 4. Duvdevani M, Nass D, Neumann Y, Leibovitch I, Ramon J, Mor Y. Pure rhabdoid tumor of the bladder. J Urol 2001;166:2337. 5. Inagaki T, Nagata M, Kaneko M, Amegei T, Iwakawa M, Watanabe T. Carcinosarcoma with rhabdoid features of the urinary bladder in a 2yearold girl: Possible histogenesis of stem cell origin. Pathol Int 2000;50:973-8. 6. Parham DM, Weeks DA, Beckwith JB. The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy. Am J Surg Pathol 1994;18:1010-29. 7. Korkolopoulou P, Christodoulou P, Kapralos P, Exarchakos M, Bisbiroula A, Hadjiyannakis M, et al. The role of p53, MDM2 and c-erb B-2 oncoproteins, epidermal growth factor receptor and proliferation markers in the prognosis of urinary bladder cancer. Pathol Res Pract 1997;193:767-75. 8. Forte S, Kos S, Hoffmann A. Unusual location of a urinary bladder cancer metastasis. Case Report. Radiology 2009;4:316. 9. Weizer AZ, Shariat SF, Haddad JL, Escudier S, Lerner SP. Metastatic transitional cell carcinoma of the urinary bladder to the shoulder girdle. Rev Urol 2002;4:97-9.

Primitive neuroectodermal tumor of ovary in a young lady, confirmed with molecular and cytogenetic results--a rare case report with a diagnostic and therapeutic challenge.

Primitive neuroectodermal tumor (PNET) is a small round cell tumor of neuroectodermal origin. It is the most differentiated form of PNET/Ewing’s family of tumors (EFT) [1]. It is the second most common sarcoma among children and usually occurs in the bone and soft tissues [2]. Ewing’s sarcoma/ PNET is characterized by a t (11; 22) (q24; q12) chromosomal translocation that leads to formation of a chimeric transcript EWS-FLI1 in 85% cases, presence of which confirms its diagnosis, especially at non-conventional sites [3]. It has been uncommonly documented at sites other than musculoskeletal system, such as kidneys [4]. PNET has been rarely documented in the female genital system, including ovary, with only few cases confirmed by molecular and / or molecular cytogenetic analysis [5–12]. Herein, we present an uncommon case of PNET involving ovary in a young lady, who presented with a pelvic mass. The diagnostic and therapeutic implications are discussed herewith.

Protocol for qRT-PCR analysis from formalin fixed paraffin embedded tissue sections from diffuse large b-cell lymphoma: Validation of the six-gene predictor score

As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S. Korea, Thailand and Turkey). Using the Kaplan-Meier and log rank test on patients (n=162) and two mortality risk groups (with those above and below the mean representing high and low risk groups) confirmed that the 6-gene predictor score correlates significantly with overall survival (OS, p<0.01) but not with event free survival (EFS, p=0.18). Adding the International Prognostic Index (IPI) shows that the 6-gene predictor score correlates significantly with high IPI scores for OS (p<0.05), whereas those with low IPI scores show a trend not reaching significance (p=0.08). This study defined an effective and economical qRT-PCR strategy and validated the 6-gene score as a predictor of OS in an international setting.

The effect of biological heterogeneity on R-CHOP treatment outcome in diffuse large B-cell lymphoma across five international regions

Abstract Addressing the global burden of cancer, understanding its diverse biology, and promoting appropriate prevention and treatment strategies around the world has become a priority for the United Nations and International Atomic Energy Agency (IAEA), the WHO, and International Agency for Research on Cancer (IARC). The IAEA sponsored an international prospective cohort study to better understand biology, treatment response, and outcomes of diffuse large B-cell lymphoma (DLBCL) in low and middle-income countries across five UN-defined geographical regions. We report an analysis of biological variation in DLBCL across seven ethnic and environmentally diverse populations. In this cohort of 136 patients treated to a common protocol, we demonstrate significant biological differences between countries, characterized by a validated prognostic gene expression score (p < .0001), but International Prognostic Index (IPI)-adjusted survivals in all participating countries were similar. We conclude that DLBCL treatment outcomes in these populations can be benchmarked to international standards, despite biological heterogeneity.