S100P as a marker for poor survival and advanced stage in gallbladder carcinoma.

AIMS: Gallbladder carcinomas usually present in advanced stages and has a dismal prognosis despite modern imaging techniques and aggressive surgical intervention. Identification of biologic markers for early diagnosis and improved therapeutic strategies is thus of paramount importance. S100P has been identified in a variety of malignant neoplasms of the gastrointestinal and pancreaticobiliary systems, but it is not yet known if S100P expression is associated with clinically-relevant characteristics of gall bladder carcinoma. The aims of the present study were: 1) to investigate the relationship between S100P expression and histological type, grade, tumor-node-metastasis stage, presence of vascular invasion, perineural invasion and necrosis; and 2) to evaluate for any S100P-defined difference in the risk for tumor recurrence or death. METHOD: Immunostains for S100P were performed on 4 tissue microarray blocks containing 91 cases of gall bladder carcinoma. RESULT: The intensity of S100P staining was significantly associated with pathological T stage 4 (p = 0. 0238). Staining intensity ≥3 in ≥25% tumor cells was associated with pathological T stage 4 (p = 0.0005). A higher S100P immunoreactivity score (IRS) was significantly associated with higher TNM stage (p = 0.0341). Age (p = 0.0485), presence of vascular invasion (p = 0.0359), pathological T stage (p = 0.0291) and TNM stage (p = 0.0153) were significantly associated with tumor recurrence. Intense S100P reactivity was associated with decreased overall survival [hazard ratio = 9.614; 95% confidence interval (CI), 1.873-49.338; p = 0.0067]. CONCLUSION: Our findings indicate that S100P over-expression is a potential prognostic marker for gall bladder carcinoma and is significantly associated with advanced tumor stage and poorer survival.

Analysis of Malignant Thyroid Neoplasms with a Striking Rise of Papillary Microcarcinoma in an Endemic Goiter Region.

According to National Cancer Registry Program, Thiruvananthapuram district of Kerala, has the highest relative frequency of thyroid carcinomas; nevertheless, limited data exist regarding its socio-demographic and clinico-pathological characteristics. The aims of the study were to assess the: (1) demographic characteristics, (2) histopathological features and the relative frequency of various thyroid carcinoma cases and papillary thyroid carcinoma (PTC) subtypes, (3) rising trend of papillary microcarcinomas, and (4) associated lesions. A retrospective study wherein 170 cases of thyroid malignancies reported in our single institution over a period of 8 years period was reviewed. PTC accounted for 97% cases, followed by medullary (n = 4; 2.4%) and follicular carcinoma (n = 1; 0.6%). There was female preponderance (p = 0.0379) with a lower median age in females (p = 0.0275). Among the PTCs, conventional type constituted 53.4% cases (n = 87), followed by microcarcinomas (n = 34; 20.9%), follicular variant (n = 28; 17.2%), and others 14 cases (8.5%). Thirty-three cases (19.4%) showed multifocality, 5 cases (2.9%) extra-thyroid extension, and 19 cases (11.2%) lymph node metastasis. Two cases developed recurrences and three cases, metastasis. The associated lesions were significantly higher in females (p = 0.0059); most common being multinodular goiter (MNG; n = 67; 41.1%), followed by Hashimoto thyroiditis (n = 44; 27%) and lymphocytic thyroiditis (n = 28; 17.2%); MNG being associated with follicular (p = 0.0129), and Hashimoto thyroiditis with conventional variant (p = 0.0475). The frequency of microcarcinomas significantly increased in the past 4 years (p = 0.0291) and was associated with MNG (p = 0.0055), Hurthle cell nodule (p = 0.0315) and absent lymph node metastasis (p = 0.0147). The primary treatment modality was total thyroidectomy. Papillary microcarcinoma cases increased significantly in the past 4 years and were significantly associated with MNG and Hurthle cell nodule. It is challenging to distinguish the various PTC subtypes as recognition of these histological variants warrants better patient management.

Post-thyroidectomy suture granuloma: A diagnosis on fine needle aspiration cytology.

Suture granulomas result from the use of nonabsorbable suture and is an infrequent complication following thyroidectomy. When they occur, suture granulomas may mimic both benign and malignant diagnoses, posing a potential diagnostic challenge. Ultrasound-guided fine needle aspiration cytology is an accurate diagnostic modality for the workup of nodules within the thyroidectomy bed. We herein present 2 cases of post-thyroidectomy suture granulomas, presenting as a painless, palpable mass in the surgical bed and occurring as a late complication of thyroidectomy that were diagnosed on fine needle aspiration cytology.

Type II ground-glass hepatocytes as a marker of hepatocellular carcinoma in chronic hepatitis B.

Ground-glass hepatocytes are seen in chronic hepatitis B virus (HBV) infection and are known to harbor pre-S mutants, which are implicated in the pathogenesis of hepatocellular carcinoma (HCC). However, the association between ground-glass hepatocytes and HCC has yet to be clearly elucidated. The aim in the present study was to investigate the association of ground-glass hepatocytes with (1) the histologic characteristics of HBV-related HCC and (2) the grade of inflammation, stage of fibrosis, serologic markers of HBV infection, HBV viral load, and α-fetoprotein levels. We evaluated 45 hepatectomy specimens from chronic HBV-infected patients: 25 with HCC and 20 without. In comparison with those without HCC, cases with HCC had a significantly higher prevalence of type II ground-glass hepatocytes (84% versus 55%, P = .0488), demonstrating a geographically clustered pattern (84% versus 45%, P = .0102) and exceeding type I in the individual samples (84% versus 35%, P = .0005). Type II ground-glass hepatocytes also had a statistically significant association with higher stages of fibrosis, being present in 21 cases (66%) with Ishak fibrosis stages 3 to 6 as compared with only 4 cases (31%) without type II ground-glass hepatocytes (P = .0176). In conclusion, type II ground-glass hepatocytes are more likely to be present in cases of HCC, growing in a clustered pattern, and are also associated with advanced fibrosis in chronic HBV infection. Our data suggest that a growth advantage or clonal proliferation of hepatocytes with mutant hepatitis B surface antigen may play a role in the pathogenesis of HBV-related HCC with clinical relevance.

Role of Foxp3-positive tumor-infiltrating lymphocytes in the histologic features and clinical outcomes of hepatocellular carcinoma.

The role of Foxp3-positive regulatory T cells (Foxp3 Tregs) in suppression of antitumoral immune response is well documented in patients with cancer. However, it is not known whether Foxp3 Tregs are associated with specific clinicopathologic characteristics of hepatocellular carcinoma (HCC). The aims of the present study were: (1) to investigate the relationship between Foxp3 Tregs and histologic differentiation, Edmondson-Steiner (ES) nuclear grade, vascular invasion, and pathologic stage of HCC in patients undergoing surgery for their disease; and (2) to evaluate any Foxp3 Treg-defined difference in the risk for tumor recurrence or death. The study sample included 131 histologic sections of HCC. The number of tumor-infiltrating CD3, CD8, and Foxp3 lymphocytes was assessed by immunohistochemistry. An increased Foxp3:CD3 ratio was associated with more poorly differentiated HCC (P=0.0016) and higher ES nuclear grade (P=0.0407). An increased Foxp3:CD8 ratio was also associated with poorer differentiation (P=0.0044), higher ES nuclear grade (P=0.0179), recurrence (P=0.0183), decreased overall survival (hazard ratio=1.153; 95% confidence interval, 1.019-1.304; P=0.0235), and decreased disease-free survival (hazard ratio=1.138; 95% confidence interval, 1.016-1.273; P=0.0249). Tumor size and type of surgery (surgical resection) were associated with decreased disease-free survival on univariate analysis but not on multivariate analysis. In conclusion, a higher concentration of tumor-infiltrating Foxp3 Tregs in HCC is associated with higher grade and poorly differentiated tumors and signifies an unfavorable prognosis.

Postmortem diagnosis of acute haemorrhagic pancreatitis.

Forensic pathologists can help in the investigation of sudden unexpected deaths in co-operation with the officials responsible for the maintenance of law and order to administer justice. Sudden unexpected deaths form the subject of medicolegal investigation if they occur in apparently healthy individuals, wherein an autopsy would shed light regarding the cause of death. A 4 year retrospective review of autopsy files at the Department of Forensic Medicine, Kasturba Medical College, Mangalore, South India was undertaken for cases of sudden unexpected deaths due to acute haemorrhagic pancreatitis occurring between May 2004 and April 2008. A total of seven cases of acute haemorrhagic pancreatitis diagnosed at autopsy as the cause of sudden unexpected death during the study period are discussed herein.

Neuronal hypertrophy and mast cells in histologically negative, clinically diagnosed acute appendicitis: a quantitative immunophenotypical analysis.

INTRODUCTION AND AIM: In about 20-25% of appendicectomies performed for clinically suspected acute appendicitis, definite morphological changes are lacking on histopathological examination. The present study was done to investigate whether any changes in neurons and mast cells could be detected in patients presenting with clinical acute appendicitis but found to have normal appendix at histopathology. METHODS: A descriptive study was conducted on 50 appendix specimens which were categorized as histology-positive acute appendicitis (HPAA), clinically acute appendicitis but histologically negative (HNAA), appendices resected for other causes and appendices from forensic autopsy. A morphometric and quantitative evaluation of nerve fibers and ganglion plexus and its relation to mast cell density were studied. All sections were subjected to hematoxylin and eosin stain, toluidine blue stain, S 100 protein and neuron specific enolase (NSE) immunostaining and a quantitative image analysis system. RESULTS: Mucosal and submucosal neuronal components highlighted by NSE and S100 immunostaining observed in cases of HNAA were comparable to cases of HPAA. With S 100 immunostaining in HNAA cases, the increase in number and size of myentric neuronal plexus were mild in 40% (10/25) cases, moderate in 40% (10/25) and marked in 20% (5/25) cases as compared to 66.7% (10/15) cases of HPAA showing moderate and 33.3% (5/15) cases showing marked increase (p = 0.018). The mean mast cell count was highest in the HNAA cases (2.74) in all the four layers as compared to the HPAA (1.85) and control group (2.05). There was no difference in the relationship of the size of ganglion cells and the mast cell concentration. CONCLUSIONS: Neuronal hypertrophy and mast cells may play a role in the pathogenesis of appendicitis-like pain in patients with histologically normal appendices.

An autopsy case of sudden unexplained death caused by malaria.

Sudden unexplained deaths, especially those unwitnessed can lead to forensic issues and would necessitate the need for a meticulous and complete postmortem examination including ancillary investigations to discover the cause of death. We herein report a case of sudden unexplained death caused by malaria in an apparently healthy individual. This fatal case is presented to remind the forensic pathologist of the possibility of malaria as a cause of sudden unexplained death in malaria-endemic regions. In the present case, histopathological examination demonstrated the presence of parasitized red blood cells with malarial pigment in the blood capillaries in the brain, myocardium, pericardium, lungs, kidneys, liver, and the spleen. Cerebral malaria with acute renal insufficiency or pulmonary edema with an acute respiratory distress syndrome might have been the cause of death.

Congenital cystic adenomatoid malformation of lung type 1.

Congenital cystic adenomatoid malformation, a rare developmental, hamartomatous abnormality of the lung, usually is unilateral, is localized, and presents in early infancy. Delayed occurrence in older children and multilobar involvement are rare. We describe a case of congenital cystic adenomatoid malformation type 1 with multilobar involvement, associated emphysema, and coexistent tracheobronchopathia osteochondroplastica in an adolescent girl for whom the correct diagnosis was achieved only on histologic examination. The importance of an accurate diagnosis of this entity enables proper subtyping, management to minimize the risk of infections and malignancy, and exclusion of associated malformations.

Rare association of papillary carcinoma of thyroid with adult T-cell lymphoma/leukemia.

Papillary carcinoma is the most common malignant tumor of the thyroid, especially in countries with adequate or excess iodine in diet. Many studies indicate that a sizable number of papillary cancer cases occur in a setting of chronic thyroiditis. But the tumor that arises more frequently in thyroiditis is malignant lymphoma. We report a rare association of papillary carcinoma of thyroid in an elderly lady with adult T-cell lymphoma/leukemia. Fine needle aspiration of the thyroid, neck nodes and evaluation of the bone marrow and peripheral blood helped in the diagnosis of papillary cancer coexisting with adult T-cell lymphoma/leukemia.

A fetal autopsy case of body stalk anomaly.

Body stalk anomaly (BSA) is a sporadic polymalformative syndrome incompatible with extrauterine life. In utero detection of BSA by two-dimensional and three-dimensional ultrasonography and magnetic resonance imaging has been well documented. We herein describe a case of body stalk anomaly diagnosed at autopsy. The fetus had a large anterior midline abdominal wall defect with eventration of the visceral organs into the amnio-peritoneal sac and a completely absent umbilical cord. The associated anomalies included club foot, absent diaphragm, genitourinary, and gastrointestinal defects. The observed congenital anomalies supported the theory of embryonic dysgenesis as the etiologic factor. One of the major objectives in the performance of fetal autopsy is to be able to detect abnormalities that can have implications in future pregnancies. Despite the negligible familial recurrence rate of the broad spectrum of anomalies associated with this abdominal wall defect, the present case of fetal autopsy indeed delights to serve the living.

Imprint cytology of pancreatoblastoma: a case report and review of the literature.

Pancreatoblastoma is a rare tumor with approximately 60 cases described in the English literature and only five case reports illustrating the cytologic findings, four by fine-needle aspiration cytology and one by imprint cytology. We herein report the sixth case diagnosed by imprint cytology. Both the cytologic and histopathologic literatures are reviewed, and the pathologic variations observed in our case are also documented.

An autopsy case of renal candidiasis.

Systemic candidiasis is the most frequently encountered opportunistic fungal infection, the kidneys being primarily affected in 80% of the cases. Most of the cases are fatal, diagnosed either very late for effective therapeutic intervention or are documented only at postmortem examination. We, herein, report a case of renal candidiasis in an elderly male who died in the hospital while undergoing treatment for head injury and multiple fractures sustained following a road traffic incident. Renal candidiasis with fungal balls obstructing the pelvicalyceal system was diagnosed at autopsy, which may have contributed to death.

Orbital melanocytoma.

PURPOSE: To report a case of intermediate grade meningeal melanocytoma presenting as a recurrent orbital mass. INTRODUCTION: Melanocytomas are rare, primary, pigmented tumors of the central nervous system, usually presenting as well-circumscribed, encapsulated, solid masses in the posterior cranial fossa and at the spinal region, often attached to the underlying dura. Orbital manifestation is rarely encountered. METHODS: Case report with computed tomography scan, magnetic resonance imaging, histology, and immunohistochemistry. RESULTS: A 40-year-old man presented with a recurrent orbital mass manifesting as progressive proptosis of the right eye of 4 years duration. The computed tomography scan and magnetic resonance imaging revealed an intraconal mass in the superior quadrant of the orbit. Histological analysis of the excision biopsy of the mass showed a highly cellular, locally infiltrating melanocytic neoplasm suggestive of an intermediate grade meningeal melanocytoma. Immunohistochemical staining for S-100 protein and HMB-45 monoclonal antibody confirmed the diagnosis. CONCLUSIONS: Recurrent intermediate grade orbital melanocytomas are rarely encountered and have to be distinguished from other topographically similar primary melanotic tumors. They have to be managed more aggressively if intracranial extension is present due to its close relation to the visual pathways.

Morphometric evaluation of endometrial blood vessels.

Five hundred endometrial specimens were studied to document the changes in blood vessels in various phases of menstrual cycle, menstrual disturbances and in unexplained infertility. Sixty-three cases were taken as control and 437 cases as study group which included cases of dysfunctional uterine bleeding (DUB), endometrial polyps, fibroids, adenomyosis, infertility and atrophic endometrium. Using light microscopy, the vascular morphology was studied. The blood vessels were concentrated more in basal layer in the proliferative phase and in functional layer in the secretory phase. Cases of complex hyperplasia and pill endometrium had significantly higher vessel concentration. Congestion and dilatation of blood vessels were significantly higher in cases of DUB. The present study showed a positive correlation between endometrial angiogenesis and menstrual disorders. The alteration in blood vessel morphology has significant role in prognosis and in various anti-angiogenic therapies.

Microwave histoprocessing versus conventional histoprocessing.

The aim of the study is to compare the histologic quality of the microwave histoprocessing with that of conventional method and to determine its positive impact on turnaround times and reduction of costs of tissue processing. One hundred and eighty-five paired tissue sections from different organs were taken. Each tissue sections were of size of 15 mm x 10 mm x 3 mm and divided into two; one set as experimental group and the other as control group. The tissues in the experimental group were further divided into six groups and processed by vacuum-microwave method according to six protocols from I to VI. Other tissues in the control group were processed by the conventional method and compared. Overall, the quality of microscopic tissue from both the methods was identical. Microwave processing shortened the time of processing without compromising the overall quality of the histologic section and was cost-effective.

Solitary rectal ulcer syndrome in childhood.

Solitary rectal ulcer syndrome is a rare disorder of childhood and usually goes unrecognised or misdiagnosed because it can mimic various other rectal entities. Here a 9-year old boy presented with bleeding per rectum and altered bowel habits. Colonoscopy revealed multiple ulcers which on histopathological examination showed features of SRUS with severe reactive changes of regeneration mimicking malignancy.

Endobronchial metastasis from renal cell carcinoma: a case report.

A 46-year-old man had primary pulmonary symptoms of intermittent fever, cough and dyspnoea. Radiological investigations revealed a mass at right hilum with right upper lobe collapse. Bronchoscopy showed a luminal mass of which the biopsy showed a tumour with predominantly clear cell change. Subsequent investigations revealed primary renal adenocarcinoma. The differential diagnosis of clear cell lung tumour is discussed. This case of endobronchial metastasis from renal cell carcinoma is being presented because of its rarity.