Bilateral adrenal cortical rests: An interesting innocuous intruder in the fallopian tubes.

ABSTRACT: Ectopic adrenal rests refer to the presence of adrenal tissue outside its normal anatomical location and are usually discovered incidentally on microscopic examination. Literature suggests its occurrence in diverse extrarenal sites, like the genitourinary system and pelvis. Our case describes the rare occurrence of ectopic adrenal rests in the walls of bilateral fallopian tubes of a 43-year-old female patient who presented with a complaint of heavy menstrual bleeding. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Gross examination revealed adenomyosis with multiple fibroids, and the same was confirmed on microscopy. Additionally, the finding of a well-encapsulated lesion on the walls of both tubes made us relook at the fallopian tubes, which showed a small bright yellow area measuring less than 0.3 cm in the walls, which was consistent with ectopic adrenal rests after ruling out the morphological differentials of Walthard cell nests, aggregates of foamy histiocytes, metastatic renal clear cell carcinoma, displaced ovarian luteinized theca cells, heterotopia of ovarian hilus cells. Immunohistochemistry showed positivity for Melan A and CK7 was negative. The present case helps in investigating the lesser-explored aspect of adrenal rest pathology. It also reiterates need for detailed observation of fallopian tubectomy specimens by pathologists during grossing to avoid overlooking of potentially intriguing entities.

Resveratrol, cancer and cancer stem cells: A review on past to future.

Cancer remains to be an unresolved medical challenge despite of tremendous advancement in basic science research and clinical medicine. One of the major limitations is due to the side effects of chemotherapy which remains to be palliative without offering any permanent cure for cancer. Cancer stem cells (CSCs) are the subpopulation of cells in tumors that remain viable even after surgery, chemo- and radio-therapy that eventually responsible for tumor relapse. Hence, by eliminating non-stem cancer cells and cancer stem cells from the patient, permanent cure is expected. Phytochemicals have been under the intensive study to target these CSCs effectively and permanently as they do not cause any side effects. Resveratrol (RSV) is one such compound attaining lot of interest in recent days to target CSCs either alone or in combination. RSV has been used by several researchers to target cancer cells in a variety of disease models, however its CSC targeting abilities are under intensive study at present. This review is to summarize the effects of RSV under in vitro and in vivo conditions along with advantages and disadvantages of its uses against cancer cells and cancer stem cells. From the first reports on phytochemical applications against cancer and cancer stem cells in 1997 and 2002 respectively followed by later reports, up to date observations and developments are enlisted from PubMed in this comprehensive review. RSV is shown to be a potential compound having impact on altering the signal transduction pathways in cancer cells. However, the effects are variable under in vitro and in vivo conditions, and also with its use alone or in combination with other small molecules. Past research on RSV is emphasizing the importance of in vivo experimental models and clinical trials with different prospective combinations, is a hope for future promising treatment regimen.

Aberrant signal transduction in Indian triple-negative breast cancer patients.

AIM OF STUDY: The aim of this study is to correlate the prominin-1 or CD133 association with functional pathway markers of cancer stemness in Indian triple-negative breast cancer (TNBC) patient samples. MATERIALS AND METHODS: TNBC samples were confirmed for the absence of hormone receptors (estrogen receptor-ER/progesterone receptor) and human epidermal growth factor receptor-2 or proto-oncogene neu or erbB2 or CD340 by immunohistochemical analysis. Formalin-fixed paraffin-embedded samples of patients were used to collect the total RNA. Then, one-step reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the cancer stemness-related transcript levels in the different samples. The RT-PCR products were analyzed semi-quantitatively on agarose gels. The band intensities of respective samples for different transcripts were analyzed by densitometry. RESULTS: TNBC-confirmed samples had shown increased levels of CD133 transcript than control tissues. Further, elevated CD133 transcripts are correlated with higher transcript levels of NOTCH1/FZD7/transforming growth factor-beta receptor Type III R/patched-1 pathway mediators. CONCLUSIONS: This work has clearly indicated that there is a correlation between CD133 and functional pathways that control cancer stem cells in TNBC. These observations may indicate the possible association between cancer stemness and TNBC malignancy.

46 XX, SRY Negative Ovotesticular DSD.

46 XX ovotesticular DSD is a rare disorder. It presents with cryptorchidism, hypospadias or ambiguous genitalia at birth, gynaecomastia in adolescent stage or infertility in adult age. We report here a 20 year old phenotypically male who presented with gynaecomastia and found to have testis on right side and left inguinoscrotal swelling consisting of ovary, uterus and fallopian tubes. Evaluation revealed SRY negative 46 XX karyotype. He underwent surgical removal of ovary and mullerian structures. The highlight of case is development of testicular tissue in absence of SRY gene.

Primary Amyloidosis - In a Case with Normal Plasma Cell Counts.

Amyloidosis is a group of disease that is characterized by the deposition of extracellular abnormal proteinaceous material (amyloid), in various organs. Amyloidosis involving the liver is common and the radiological findings are often nonspecific. We present the case of a 40-year-old female who presented with abdominal pain. Ultrasound abdomen was reported as massive hepatomegaly with diffuse liver parenchymal disease. Bone marrow aspiration showed normomegaloblastic erythroid hyperplasia and plasma cells were within normal limits (5%). Also, amorphous, eosinophilic fragmented to smudgy material within the interstitium of cell trails was seen. Bone marrow biopsy and liver biopsy also showed similar kind of homogenous eosinophilic material. Both liver biopsy and bone marrow biopsy were subjected to special stains which confirmed the presence of amyloid. The patient did not have clinical or laboratory findings suggestive of any other organ involvement. Thus, we conclude that clinical and imaging presentations of amyloidosis are often nonspecific, hence biopsy is always required to confirm the diagnosis. Amyloid deposits on bone marrow aspiration are a rare occurrence and are often missed. It is an unusual sighting with very few studies mentioning its occurrence.

Avascular Necrosis of Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic and Histopathological Characterization.

Avascular necrosis of the femur head (AVNFH) is a debilitating disease caused due to the use of alcohol, steroids, following trauma or unclear (idiopathic) etiology, affecting mostly the middle aged population. Clinically AVNFH is associated with impaired blood supply to the femoral head resulting in bone necrosis and collapse. Although Homocysteine (HC) has been implicated in AVNFH, levels of homocysteine and its associated pathway metabolites have not been characterized. We demonstrate elevated levels of homocysteine and concomitantly reduced levels of vitamins B6 and B12, in plasma of AVNFH patients. AVNFH patients also had elevated blood levels of sodium and creatinine, and reduced levels of random glucose and haemoglobin. Biophysical and ultrastructural analysis of AVNFH bone revealed increased remodelling and reduced bone mineral density portrayed by increased carbonate to phosphate ratio and decreased Phosphate to amide ratio together with disrupted trabeculae, loss of osteocytes, presence of calcified marrow, and elevated expression of osteocalcin in the osteoblasts localized in necrotic regions. Taken together, our studies for the first time characterize the metabolomic, pathophysiological and morphometric changes associated with AVNFH providing insights for development of new markers and therapeutic strategies for this debilitating disorder.

Ectopic Parathyroid Adenoma Presenting as a Mediastinal Mass.

A parathyroid adenoma present in an ectopic site, in the anterior mediastinum, is a rare cause of persistent hyperparathyroidism. Though its occurrence in the mediastinum is unusual, existence has been noted in literature for more than a century. We describe a case of a 35-year-old male presenting with complaints of pain abdomen, clinically diagnosed as acute necrotizing pancreatitis, with raised serum calcium. Patient received symptomatic treatment for the pancreatitis which subsided. However, high levels of serum calcium persisted. Suspecting hyperparathyroidism, ultrasound neck was done, revealing apical thoracic mass. CT scan of neck revealed a large heterogeneous enhancing mass in superior mediastinum. Fine Needle Aspiration (FNA) of the mass done endoscopically was confusing as it showed features suggestive of a cystic teratoma. However, persistently raised calcium levels along with raised parathormone warranted a Technetium - 99 (Tc-99m) sestamibi scan which revealed positive uptake involving right inferior parathyroid extending to superior mediastinum. The mass was surgically excised and it was diagnosed as a parathyroid adenoma. This case helps bring to light the necessity to consider ectopic parathyroid adenoma as an important differential diagnosis in mediastinal tumour with persistent hypercalcaemia, and as a cause of hyperparathyroidism.

Oral Spindle Cell Sarcoma: A Rare Case Report and Review of Literature.

Spindle cell lesions of the head and neck region are diverse in nature by means of clinical and biological heterogeneity. Though few lesions are found to be malignant, several others are benign or merely reactive in nature. Although these lesions are fairly common occurring in other parts of the body, they are very rare in the oral cavity, accounting for less than 1% of all tumours in the oral region. Herein, a case of 48-year-old man who presented with a polypoid lesion of the maxilla has been reported. Histopathological examination and immunohistochemistry revealed spindle cell sarcoma of the left maxillary sinus. We present this rare tumour to contribute to the better understanding and awareness of this rare malignancy where diagnosis can be very challenging.

Expression of Epstein-Barr virus among oral potentially malignant disorders and oral squamous cell carcinomas in the South Indian tobacco-chewing population.

BACKGROUND: Oral cancer is the sixth most common malignancy in the world. Viruses are the causative agents of approximately 10-15% of all cancers worldwide (Cancers, 6, 2014 and 2155). The tumorigenic roles of Epstein-Barr virus in oral cancer are unclear. Literature search results are conflicting and dependent on various factors such as geographical/regional variations, sociocultural lifestyles, dietary habits, chewing/smoking tobacco habit. This study is the first original observation about frequency of Epstein-Barr virus among South Indian tobacco-chewing patients to elucidate its involvement in oral carcinogenesis and to know whether this can be a valuable diagnostic and prognostic indicator. MATERIALS AND METHODS: A total number of 75 tobacco chewer subjects aged between 23 and 76 years with histopathologically confirmed oral potentially malignant disorders (25), oral squamous cell carcinoma (25), and age-matched healthy controls (25) formed the study group. Immunohistochemical expression of Epstein-Barr virus latent membrane protein 1 was assessed among cases and healthy controls. RESULTS: Out of the total 75 subjects, six subjects (8%) were positive for Epstein-Barr virus antigen and 69 subjects (92%) negative. The antigen positivity was observed among two cases of moderately differentiated oral squamous cell carcinoma, two cases of leukoplakia, and two healthy controls. CONCLUSION: No significant association between Epstein-Barr virus positivity was observed among oral potentially malignant disorders and oral squamous cell carcinoma among South Indian tobacco-chewing patients. This can be partially explained by the methodology employed, by the patient population analyzed and different habits in various geographical regions.

Clinical features and histological patterns of lupus nephritis in a single center of South India.

Renal involvement occurs in up to 60% of patients with systemic lupus erythematosus (SLE) and signifies a poor prognosis. The class of lupus nephritis (LN), determined on renal biopsy evaluation, guides the therapeutic management and has prognostic connotations. Our aim is to determine the clinicolaboratory features and histopathological patterns of LN at presentation in our local (South Indian) population. The study was conducted in a tertiary care hospital in South India between 2009 and 2014 on SLE patients with clinical evidence of LN. The renal biopsies were examined by light and immunofluorescence microscopy and were classified according to the International Society of Nephrology/Renal Pathology Society Classification of LN. A total of 46 patients were included, with age range of 12-60 years and a female to male ratio of 8.2:1. Arthritis, dermatological manifestations, and fever occurred, respectively, in 43.5%, 39.1%, and 30.4% of the cases. Class IV LN was present in 17 (37.1%), Class III LN in ten (21.7%), Class II LN in nine (19.5%), Class V LN in eight (17.4%), Class I LN in one (2.2%), and Class VI LN in one (2.2%) patients. Antinuclear antibody (ANA) and dsDNA positivity were present, respectively, in 82.6% and 65.2% of the patients. The most common pattern of LN was Class IV LN followed by Class III LN. Relatively higher proportions of ANA and anti-dsDNA positivity were present in proliferative LN, and there was a high frequency of arthritis at presentation in our LN patients.

Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study.

BACKGROUND: Recent studies have revealed the involvement of hedgehog (Hh) signaling component in proliferation and invasive behavior of many carcinomas. AIM: This study aims to identify the expression of sonic Hh (SHH) protein of SHH pathway in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) using SHH (H-160) (Santa Cruz, sc-9042) which could have therapeutic implication in future. MATERIALS AND METHODS: A total of 250 cases comprising 50 normal oral mucosa, 50 cases of oral epithelial dysplasia, 50 well, 50 moderate and 50 poorly differentiated OSCCs were included in the study. Immunohistochemical evaluation of SHH protein expression was conducted using monoclonal antibody. Interpretation of the expression was done by immunoreactive score of Remmele and Stegner (IRS) scoring method. STATISTICAL ANALYSIS: Chi-Square test was used to analyze the results. RESULTS: The study showed that SHH signaling molecules are highly expressed in OSCC, and their expression was mainly in the cytoplasm of epithelial cells. CONCLUSION: The SHH signaling component is associated with the pathological parameter in OSCC and oral epithelial dysplasia.

Correlation of p53 Overexpression with the Clinicopathological Prognostic Factors in Colorectal Adenocarcinoma.

INTRODUCTION: Mutation in p53 gene and accumulation of p53 protein is a common genetic event in colorectal carcinomas. p53 mutation can be detected by various techniques such as DNA sequencing, polymerase chain reaction and immunohistochemistry (IHC). However, IHC is simple and is consistent with other techniques. AIM: To establish a correlation between overexpression of p53 with the clinical features, tumour histopathology and stage of Colorectal Carcinoma (CRC). MATERIALS AND METHODS: This prospective and retrospective study of clinical, histopathological and IHC features of CRC was conducted on colectomy and abdomino-perineal resection specimens received from January 2008 to June 2013. For each case, the clinical features, tumour morphology and p53 status (by IHC) were evaluated. RESULTS: The most common histologic type of CRC was Non-Specific Type (NST) and grade II tumours were seen predominantly (60%). Overall, 67.5% of CRCs showed p53 positivity on IHC. Intense p53 positivity was observed in 37.5% of CRCs of NST type and 33.3% of mucinous adenocarcinomas showed moderate positivity. Grade III tumours showed variable p53 positivity and those with lymph node metastasis showed moderate (55.6%) or intense positivity (53.8%). But there was no statistically significant correlation of p53 status and various clinicopathological prognostic factors. CONCLUSION: As p53 protein overexpression is seen in a relatively high percentage of CRCs, it seems that p53 mutation plays an important role in development of CRC. However, no direct correlation could be established between p53 results and the patients' age, sex, tumour site, size, histological type, grade, lymph node status, or TNM stage. A prolonged follow up is necessary to conclude whether p53 status has any influence on the long, term prognosis and patient survival.

Variant Philadelphia translocations in chronic myeloid leukemia: A report of five cases.

The t (9;22)(q34;q11) translocation is found in about 90% of the chronic myeloid leukemia patients. About 5-10% of these patients have complex variant translocations involving a third chromosome in addition to chromosomes 9 and 22. We describe five male patients in the chronic myeloid leukemia-chronic phase, with rare variant Philadelphia translocations. All of them had the BCR-ABL fusion gene and responded well to treatment with imatinib mesylate. All the patients are on regular follow-up.

Inflammatory pseudotumor of kidney masquerading as renal carcinoma.

Inflammatory pseudotumor also known as inflammatory fibroblastic tumor is a rare benign tumor, which commonly affects the lung. It is very rarely seen in the genitourinary tract. As the preoperative diagnosis, clinically and radiologically is inconclusive, it is imperative to surgically remove and confirm it on histopathologic examination. We report a case of inflammatory pseudotumor in a 51-year-old male who presented with flank pain and was treated with nephrectomy.

Role of direct immunofluorescence in dermatological disorders.

BACKGROUND: Direct immunofluorescence (DIF) test for tissue-bound autoantibodies, has been found to be of value in the diagnosis of several dermatological disorders. The location and pattern of deposition of immunoreactants helps in classifying various immune-mediated diseases. AIMS AND OBJECTIVES: The aim of this study was to analyze the concordance between the clinical, histopathological and DIF diagnosis in bullous and nonbullous lesions of the skin, and thus determine the impact of immunofluorescence on diagnosis. MATERIALS AND METHODS: A total of 215 skin biopsies performed in suspected immune-mediated vesiculobullous disease, vasculitis or dermatosis, were studied. Histopathological examination was done along with DIF study for deposits of immunoglobulin G(IgG), IgA, IgM, and C3. RESULTS: Direct immunofluorescence was positive in 103/215 cases. There was very good concordance between the clinical, histological and DIF results (observed agreement = 93.4%, κ =0.90, with 95% confidence interval = 0.86-0.94). The overall sensitivity of DIF in immune-mediated skin disorders was 98.0%. DIF was positive in 52/53 cases (98.1%) in the pemphigus group and 24/25 (96.0%) bullous pemphigoid cases. None of the clinically suspected cases of dermatitis herpetiformis showed DIF positivity. A positive lupus band test was seen in 9/9 (100%) cases of lupus erythematosus. DIF was positive in 10/10 (100%) clinically suspected cases of Henoch-Schönlein purpura. In 110 cases, negative DIF results helped to rule out immune-mediated vesiculobullous disorders, lupus erythematosus and vasculitis, and the final diagnosis was made on the basis of the clinical features and/or histopathology. CONCLUSION: Direct immunofluorescence is a useful supplement for the accurate diagnosis of immune-mediated dermatological disorders, and helps to classify various autoimmune bullous disorders. When the clinical features/histopathology are inconclusive, the diagnosis often can be made on the basis of the DIF findings alone. A combination of the clinical features, histopathology and DIF usually gives the best results.

Maxillary osteosarcoma masquerading as chondromyxoid fibroma: report of a case.

Osteosarcomas are highly malignant bone tumours. Its appearance in craniofacial bones is a rare entity and accounts for only 1% of all head and neck malignancies. We present an uncommon case report of a 42 year old male patient with osteosarcoma of left maxilla, which was successfully excised under general anesthesia. The patient reported to us with a history of pain, swelling, pus discharge and tooth extraction, which led to the differential diagnosis of suppurative osteomyelitis, dentoalveolar abscess, benign odontogenic tumour, an infected cyst etc. Histopathological examination of incisional biopsy was reported as chondromyxoid fibroma which is a rare benign tumour. However the excisional biopsy specimen was reported as osteosarcoma of maxilla. The clinical presentation, diagnostic challenges and its therapeutic approach are addressed. This case serves to emphasize the need to recognize osteosarcoma when it presents in unexpected locations, especially because of its rarity.

Unusual fungal infections in renal transplant recipients.

Fungal infections are an important cause of morbidity and mortality in renal transplant recipients. The causative agent and the risk factors differ depending on the period after the kidney transplant. Also the incidence varies according to the geographical area. We are reporting three cases of fungal infections in renal transplant recipients. Two of them have etiological agents which are common among immunosuppressed patients, but with an atypical clinical presentation, while one of them is a subcutaneous infection caused by a less frequent dematiaceous fungus, Aureobasidium pullulans. These cases highlight how a high index of clinical suspicion and prompt diagnosis is very much essential for better outcome. The emerging fungal infections and paucity of data regarding their management pose a challenge to the transplant physicians.

Hepatic angiosarcoma developing in an infantile hemangioendothelioma: A rare case report.

Angiosarcomas are rare tumors that predominantly affect adults. Hepatic angiosarcoma in a child is extremely rare and associated with a poor prognosis. Herein, we report the pathologic features of a hepatic angiosarcoma developing in a 31/2-year-old child who had been earlier diagnosed and was being treated for hepatic hemangioendothelioma.

Primary Extranodal Lymphomas of Lip - A Rare Manifestation in Sjogren's Syndrome.

Sjogren's syndrome (SS) is a chronic autoimmune disorder which is characterized by lymphocyte-mediated destruction of exocrine glands, which produces the classical symptoms of dry eyes and dry mouth, which is referred to as primary SS or the Sicca complex. When it is associated with another autoimmune disease such as rheumatoid arthritis or lupus erythematosus, the condition is termed as secondary SS. One of the known major complications in patients with Sjogren's syndrome is the occurrence of Non-Hodgkin's lymphoma of B cell type. It is not uncommon for malignant lymphomas to occur in head and neck region at nodal and sometimes, extranodal sites. However, only rarely may they involve the oral cavity primarily. This case report describes a rare occurrence of isolated extranodal lymphomas in the upper and lower lips of a patient, which clinically resembled a mucocele, and eventually was diagnosed as lymphoma which was associated with Sjogren's syndrome, thereby stressing the importance which was played by an oral diagnostician.