Primary Leiomyosarcoma of the Mesentery: A Case Report.

Mesenteric masses are infrequent lesions ranging from benign cysts to aggressive malignancies and often present a diagnostic and therapeutic challenge. The mesentery is a frequent recipient of metastases from the gastrointestinal tract, pancreas, and biliary cancers. Primary mesenteric tumors are relatively rare, mostly mesenchymal in origin and benign in nature. Examples include gastrointestinal stromal tumors and smooth muscle tumors. We describe a 50-year-old woman, who presented with a lump in the left hypochondrium along with altered bowel habits of 2 years' duration. Imaging revealed a cystic lesion, raising the differentials of a benign lesion. Exploratory laparotomy revealed a large cystic mass in the mesentery closely abutting the jejunal loops. This was followed by mass resection along with a segment of the jejunum. Histopathological examination revealed features of a leiomyosarcoma. Postoperatively, the patient developed a colocutaneous fistula, which was re-excised. At 6 months' follow-up, the patient is doing well. Our case demonstrates the diagnostic challenge posed by the atypical clinical and imaging features of this tumor at an unusual site.

Expression and humoral response of A-kinase anchor protein 4 in cervical cancer.

BACKGROUND: Cervical cancer is one of the major gynecologic cancers. In developing countries, because of a lack of medical support and infrastructure, cervical cancer is the leading cause of cancer-related deaths. Therefore, there is a need to identify novel biomarkers for cervical cancers. In this context, cancer-testis (CT) antigens represent a unique class of tumor antigens that have been shown to be associated with various solid tumors. These antigens have restricted expression in testis and no expression in somatic tissues. Because of their restricted expression, CT antigens are novel candidate molecules for early detection and diagnosis and immunotherapy. In the present study, novel CT antigen A-kinase anchor protein 4 (AKAP4) expression and humoral response were investigated in patients with cervical cancer. METHODS: In this study, 74 cervical cancer tissue specimens, which included different tumor stages (stage I [n = 35], stage II [n = 39]) and histologic grades (grade 1 [n = 17], grade 2 [n = 46], and grade 3[n = 11]) and 62 adjacent noncancerous tissue specimens were investigated for AKAP4 gene expression by using reverse transcriptase polymerase chain reaction and in situ RNA hybridization. Furthermore, AKAP4 protein expression was determined by immunohistochemistry. In addition, humoral response against purified recombinant AKAP4 protein was determined in available sera of 70 patients with cervical cancer by enzyme-linked immuno assay (ELISA). FINDINGS: Our study revealed that AKAP4 gene and protein expression was detected in 86% of total patients with cervical cancer. Based on the AKAP4 immunoreactivity score, most of stage I (n = 22/29) and stage II (n = 30/35) specimens revealed high AKAP4 expression (≥50% AKAP4-positive cells). A-kinase anchor protein 4 expression was significantly associated with early grades tumor specimens (P = 0.023). In addition, humoral response was detected in 53% of patients irrespective of stages, lymph node positivity, and grades. CONCLUSIONS: Collectively, our data indicate the putative role of AKAP4 in early tumorigenesis and may be implicated as a biomarker and immunotherapeutic target for cervical cancer.

Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors.

BACKGROUND & OBJECTIVES: Breast cancer is the second most common malignancy in Indian women. Among the members of the steroid receptor superfamily the role of estrogen and progesterone receptors (ER and PR) is well established in breast cancer in predicting the prognosis and management of therapy, however, little is known about the clinical significance of androgen receptor (AR) in breast carcinogenesis. The present study was aimed to evaluate the expression of AR in breast cancer and to elucidate its clinical significance by correlating it with clinicopathological parameters, other steroid receptors (ER and PR) and growth factors receptors (EGFR and CD105). METHODS: Expression of AR, ER, PR, epidermal growth factor receptor (EGFR) and endoglin (CD105) was studied in 100 cases of breast cancer by immunohistochemistry (IHC). Risk ratio (RR) along with 95% confidence interval (CI) was estimated to assess the strength of association between the markers and clinicopathological characteristics. Categorical principal component analysis (CATPCA) was applied to obtain new sets of linearly combined expression, for their further evaluation with clinicopathological characteristics (n=100). RESULTS: In 31 cases presenting with locally advanced breast cancer (LABC), the expression of AR, ER, PR, EGFR and CD105 was associated with response to neoadjuvant chemotherapy (NACT). The results indicated the association of AR+ (P=0.001) and AR+/EGFR- (P=0.001) with the therapeutic response to NACT in LABC patients. The AR expression exhibited maximum sensitivity, specificity and likelihood ratio of positive and negative test. The present results showed the benefit of adding AR, EGFR and CD105 to the existing panel of markers to be able to predict response to therapy. INTERPRETATION & CONCLUSIONS: More studies on the expression profiles of AR+, AR+/CD105+ and AR+/EGFR- in larger set of breast cancer patients may possibly help in confirming their predictive role for therapeutic response in LABC patients.

Choroid, a unique site for metastasis in Marjolin's ulcer.

Marjolin is an aggressive malignancy, which shows initial local aggression, followed by the rapid regional and distant dissemination during the latter part of its growth. Metastasis to the uveal tract, although infrequent, is usually secondary to the malignancies of the breast and lung. Marjolin's ulcer metastasizing to choroid is quite rare and unheard of. We intend to report one such case here. Here, we present a case report of a 55-year-old male, who developed Marjolin's ulcer over a previously injured left lower limb. He developed recurrence and re-recurrences requiring multiple surgeries, radiation, and chemotherapy cycles. He eventually developed disseminated systemic metastases. Over the course of his disease, he reported eye symptoms of pain, blurring of vision, and field defect in the left eye. On further evaluation with imaging and fundoscopy, a metastatic deposit was identified in the choroid of the left eye. Metastasis to the uveal tract is an unusual unreported event in the disease progression of Marjolin's ulcer. The treatment is usually palliative. It heralds the terminal stage of the disease, with inevitable death.

Collision of Malignant Melanoma and Squamous Cell Carcinoma in Rectum: First Report of a Rare Tumor.

The term collision tumor is used to describe two neoplasms occurring in the same anatomic location with juxtaposition of different tumor elements. Such a coexistence of tumors anywhere in the body is relatively rare. We report a case of 32-year-old female with collision tumor of rectum. The tumor showed two distinct histological patterns with predominant component consisting of malignant melanoma and a minor component of squamous cell carcinoma. The morphological picture of collision was further confirmed by specific immunohistochemical profile of the two tumors. Collision tumors of rectum are uncommon with most of the reported cases comprising adenocarcinoma and neuroendocrine tumors. To the best of our knowledge this is the first case of collision tumor of malignant melanoma and squamous cell carcinoma in the rectum.

Cluster of Differentiation 10 Positive Stromal Sarcoma of Breast: A Diagnostic Challenge.

Stromal sarcomas of the breast are a group of rare and heterogeneous tumors which mimic malignant phylloides tumor and metaplastic carcinoma histologically. These tumors have been reported in the literature mostly in form of small retrospective case series and case reports, making it difficult to characterize their exact histopathological spectrum and management strategy. Our patient was a 65-year-old female who presented with a 3-month history of a lump in the left breast. Examination revealed an immobile mass in upper and outer quadrant of left breast, 5 x 4 cm in diameter. Trucut biopsy revealed sheets of atypical spindle cells. She underwent a modified radical mastectomy. On histopathology, we found malignant mesenchymal tumor positive for vimentin and cluster of differentiation 10 (CD10). Thus, a rare diagnosis of CD10 positive mammary stromal sarcoma was established. The case has been reported for its rarity and to highlight the importance of a meticulous histopathological examination for excluding close differentials.

Study of Gene Expression Profiles of Breast Cancers in Indian Women.

Breast cancer is the most common cancer among women globally. In India, the incidence of breast cancer has increased significantly during the last two decades with a higher proportion of the disease at a young age compared to the west. To understand the molecular processes underlying breast cancer in Indian women, we analysed gene expression profiles of 29 tumours and 9 controls using microarray. In the present study, we obtained 2413 differentially expressed genes, consisting of overexpressed genes such as COL10A1, COL11A1, MMP1, MMP13, MMP11, GJB2, and CST1 and underexpressed genes such as PLIN1, FABP4, LIPE, AQP7, LEP, ADH1A, ADH1B, and CIDEC. The deregulated pathways include cell cycle, focal adhesion and metastasis, DNA replication, PPAR signaling, and lipid metabolism. Using PAM50 classifier, we demonstrated the existence of molecular subtypes in Indian women. In addition, qPCR validation of expression of metalloproteinase genes, MMP1, MMP3, MMP11, MMP13, MMP14, ADAMTS1, and ADAMTS5 showed concordance with that of the microarray data; wherein we found a significant association of ADAMTS5 down-regulation with older age (≥55 years) of patients. Together, this study reports gene expression profiles of breast tumours from the Indian subcontinent, throwing light on the pathways and genes associated with the breast tumourigenesis in Indian women.

Sperm-associated antigen 9, a novel cancer testis antigen, is a potential target for immunotherapy in epithelial ovarian cancer.

PURPOSE: Cancer testis antigens are a group of tumor antigens with gene expression restricted to male germ cells in the testis and in various cancerous tissues. Recently, we reported a novel testis-specific sperm-associated antigen 9 (SPAG9) gene, a new member of the c-Jun NH(2)-terminal kinase-interacting protein family, having functional role in sperm-egg fusion and mitogen-activated protein kinase signaling pathway. National Center for Biotechnology Information Blast searches revealed SPAG9 nucleotide sequence similarities with expressed sequence tags of various cancerous tissues. In an effort to examine the clinical utility of SPAG9, we investigated the SPAG9 mRNA and protein expression in epithelial ovarian cancer (EOC). Humoral immune response to SPAG9 was also evaluated in EOC patients. EXPERIMENTAL DESIGN: We determined the expression profile of SPAG9 transcript by reverse transcription-PCR and RNA in situ hybridization and SPAG9 protein expression by immunohistochemistry in EOC specimens and human ovarian cancer cell lines. Using ELISA and Western blotting, we analyzed specific antibodies for SPAG9 in sera from patients with EOC. RESULTS: SPAG9 mRNA and protein expression was detected in 90% of EOC tissues and in all three human ovarian cancer cell lines. Specific SPAG9 antibodies were detected in 67% of EOC patients and not in sera from healthy individuals. CONCLUSIONS: Our findings indicate that SPAG9 is highly expressed in EOC and immunogenic in patients. Humoral immune response against SPAG9 in early stages of EOC suggests its important role in early diagnostics. These results collectively suggest that SPAG9, a novel member of cancer testis antigen family, could be a potential target for the development of diagnostic and therapeutic methods in EOC.

A Rare Case of Giant Solitary Neurofibroma of Abdominal Wall Masked by Pregnancy.

Various types of neurogenic tumours can involve the abdomen. Retroperitonial space is most commonly affected but other sites can also be involved. Mostly younger age group is affected and malignant transformation is rare. CT and MRI are helpful in making diagnosis and planning surgery. Complete surgical excision is treatment of choice. Final diagnosis is made by histopathology and immunohistochemistry report. We report a rare case of giant solitary benign neurofibroma of anterior abdominal wall in 25-year-old multiparous women reported on day 15 of vaginal delivery with large abdominal mass which was masked before because of pregnancy.

Isolated splenic metastasis from colorectal mucinous carcinoma.

Metastatic tumors of the spleen are rare and occur in the presence of disseminated visceral metastasis. Isolated splenic metastases from colorectal carcinoma are rare and only 19 cases have been reported in English literature. We report a case of isolated splenic metastasis in a 52-year-old man, occurring 9 years after the primary colorectal mucinous carcinoma was treated by anterior resection. The patient underwent splenectomy along with adjuvant chemotherapy and is alive and asymptomatic at 22 months follow-up.

Clear cell odontogenic carcinoma: a diagnostic and therapeutic dilemma.

BACKGROUND: Clear cell odontogenic carcinoma is a rare odontogenic tumor occurring in the anterior region of the mandible in 5th-7th decades and shows a female preponderance. It is potentially aggressive, capable of frequent recurrences and loco-regional and distant metastases. CASE PRESENTATION: A 45-year-old woman presented with a radiolucent left mandibular swelling associated with loss of teeth. Left cervical lymph nodes were enlarged on palpation. The patient underwent resection of the tumor but consequent to resected margins being positive for tumor cells underwent left hemimandibulectomy with ipsilateral functional neck dissection and was free of recurrence at 8 months follow-up. CONCLUSION: Clear cell odontogenic carcinoma should be considered in the differential diagnosis of jaw tumors with conspicuous clear cell component. Curettage or conservative resection inevitably results in recurrences and/or metastasis and more radical resection is warranted in these tumors, especially when they are large and show soft tissue invasion.

Pancreatic Tuberculosis with Markedly Elevated CA 19-9 Levels: A Diagnostic Pitfall.

Despite the high prevalence of tuberculosis (TB) in developing countries, isolated pancreatic TB is rare and is usually seen in immunocompromised patients. It presents with non-specific signs and symptoms and may mimic malignancy both clinically and radiologically. Cytologic and histologic confirmation is required to establish the definitive diagnosis. We present a case of a 25-year-old male with a pancreatic mass and markedly elevated serum cancer antigen (CA) 19-9 levels raising the suspicion of malignancy but with a histopathologic picture of TB. This case suggests that clinicians should have a heightened suspicion of pancreatic TB when faced with discrete pancreatic lesions even though elevated tumor markers may indicate malignancy. It is important to perform appropriate diagnostic testing and initiate antitubercular therapy early.

Emperipolesis in a common breast malignancy. A case report.

BACKGROUND: Emperipolesis is a phenomenon characterized by the presence of leukocytes/lymphocytes within the cytoplasm of other cells. The present report describes this unusual observation within epithelial cancer cells of the breast. CASE: A 52-year-old female presented with a hard, adherent lump over the right breast for one year. Fine needle aspiration and histopathologic examination of the tumor showed features of infiltrating duct carcinoma with emperipolesis as a striking feature of the tumor cells. The tumor showed a near-total response to neoadjuvant chemotherapy. CONCLUSION: The mechanism and biologic significance of emperipolesis in producing a near-total response to neoadjuvant chemotherapy in the present case suggest its role in inducing a tumoricidal effect, possibly involving a cascade of chemokines.

A novel cancer testis antigen, A-kinase anchor protein 4 (AKAP4) is a potential biomarker for breast cancer.

BACKGROUND: Breast cancer is the second leading cause of cancer related deaths in women worldwide. Reports about the early diagnosis of breast cancer are suggestive of an improved clinical outcome and overall survival rate in cancer patients. Therefore, cancer screening biomarker for early detection and diagnosis is urgently required for timely treatment and better cancer management. In this context, we investigated an association of cancer testis antigen, A-Kinase anchor protein 4 (AKAP4) with breast carcinoma. METHODOLOGY/FINDINGS: We first compared the AKAP4 gene and protein expression in four breast cancer cells (MCF7, MDA-MB-231, SK-BR3 and BT474) and normal human mammary epithelial cells. In addition, 91 clinical specimens of breast cancer patients of various histotypes including ductal carcinoma in situ, infiltrating ductal carcinoma and infiltrating lobular carcinoma and 83 available matched adjacent non-cancerous tissues were examined for AKAP4 gene and protein expression by employing in situ RNA hybridization and immunohistochemistry respectively. Humoral response against AKAP4 was also investigated in breast cancer patients employing ELISA. Our in vitro studies in all breast cancer cells revealed AKAP4 gene and protein expression whereas, normal human mammary epithelial cells failed to show any expression. Using in situ RNA hybridization and immunohistochemistry, 85% (77/91) tissue specimens irrespective of histotypes, stages and grades of breast cancer clinical specimens revealed AKAP4 gene and protein expression. However, matched adjacent non-cancerous tissues failed to display any AKAP4 gene and protein expression. Furthermore, humoral response was observed in 79% (72/91) of total breast cancer patients. Interestingly, we observed that 94% (72/77) of breast cancer patients found positive for AKAP4 protein expression generated humoral response against AKAP4 protein. CONCLUSIONS: Collectively, our data suggests that AKAP4 may be used as serum based diagnostic test for an early detection and diagnosis of breast cancer and may be a potential target for immunotherapeutic use.

Malignant melanoma and basal cell carcinoma of the face: a rare coexistence.

The simultaneous presence of two disparate neoplasms occurring in the same specimen has been well documented, albeit uncommonly. The juxtaposition of malignant melanoma (MM) and basal cell carcinoma (BCC) as collision tumors has been rarely reported, with most cases describing melanoma in situ and BCC. We report a case of a 20-year-old male presenting with three papillomatous growths on the face, localized over the left frontotemporal region, below the right eye and over the right eyebrow. On histopathology and immunohistochemistry the lesions were diagnosed as pigmented MM and BCC. MM and BCC presenting at different sites on the face in the same patient along with a focus of metastasis in the same anatomical region as the primary tumor is quite rare. To the best of our knowledge this is the first report of such a case.

Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells) was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042) and low grade tumors (P = 0.002) suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.

Metastasizing granular cell ameloblastoma.

Ameloblastoma is a slow growing odontogenic epithelial tumor of jaw. It accounts for 1% of all tumors and cysts arising in maxilla and mandible. Although it is locally invasive and has a marked tendency to recur, metastasis is rare. Of the various histological patterns of ameloblastoma, the granular cell type is extremely rare accounting for 4% of ameloblastomas. We report a case of granular cell ameloblastoma with metastasis to the cervical lymph node presenting in a 40-year-old Indian female.

Reconstruction of abdominal wall by whole thigh flap.

Closure of extensive abdominal wall defects can be a very challenging task as there are no known large local or free vascularized flaps available that could cover the entire abdomen. Tensor fascia latae (TFL) has been widely used for abdominal wall reconstruction [Hill HL, Nahai F, Vasocnez LO. The tensor fascia lata myocutaneous free flap. Plast Reconstr Surg 1978;61:517-22]. However, the dimensions of the standard TFL flap limit its use in cases of large full thickness abdominal wall defects. Therefore, we have used an ingenious technique of raising the entire thigh skin as a fasciocutaneous flap (whole thigh flap) based on the concept of fusion of angiosomal territories, to reconstruct such a defect following excision of a large abdominal wall tumour.