Salivary duct carcinoma: clinicopathological and immunohistochemical studies

The SCID-II Personality Questionnaire, modified for DSM-IV and ICD-10 Diagnostic Criteria for Research (ICD-10-DCR), was administered to 58 consecutive patients with agoraphobia with panic disorder in order to screen for personality disorders (PDs) and assess diagnostic agreement between DSM-IV and ICD-10-DCR. The diagnostic agreement, as expressed by kappa values, was 0.78 for the presence of any personality disorder (PD), but it ranged from 0.51 for schizoid PD to 0.83 for dependent PD. There was a tendency for ICD-10-DCR to overdiagnose PDs, except for borderline and dependent PDs. The sources of disagreement can be traced to differences in the conceptualization of some PDs and differences in diagnostic criteria and diagnostic thresholds; these are further examined in an effort to improve diagnostic criteria and attain greater compatibility between the two diagnostic systems.     

Enteric differentiation in endometrial adenocarcinomas: a mucin histochemical study

A histochemical study revealed focal intracytoplasmic mucin within 50% of a series of adenocarcinomas arising within the endometrium. Seventeen percent of the adenocarcinomas studied contained intracytoplasmic O-acetylated sialomucins, as demonstrated by the PB/KOH/PAS technique. The presence of O-acetylated sialomucin, indicating enteric or intestinal differentiation, has not previously been demonstrated within endometrial adenocarcinomas, although it is well described in endocervical adenocarcinomas and in mucinous tumors of the ovary. In none of the cases in which enteric-type mucins were identified was there morphological evidence of intestinal differentiation in the form of goblet cells or Paneth cells. No correlation was found between the presence of enteric mucins and the grade of the adenocarcinoma. The results of the study provide further confirmation of the ability of the epithelial lining of the female genital tract to undergo various forms of metaplasia, along both Mullerian and non-Mullerian pathways. The demonstration of specific mucins is more sensitive than morphology in establishing enteric differentiation.     

Medullary carcinoma of the thyroid: histomorphological, histochemical and immunohistochemical analysis of twenty cases

Histomorphological patterns of twenty primary medullary carcinomas of the thyroid were studied by light and polarized microscopy in relation to the content of calcitonin and thyroglobulin determined by the immunoperoxidase method: Out of 20 tumors, 10 showed classical, 7 glandular and 3 insular histomorphological pattern. In 19/20 cases, the cytoplasm of tumor cells contained various amounts of calcitonin, and the intensity of Immunoreaction was strong in 2/19, moderate in 7/19 and weak in 10/19 cases. Tumor stroma contained calcitonin in 7/20 cases. In 1/20 case, which did not show calcitonin immunoreactivity in the cell cytoplasm, the stroma contained a considerable amount of calcitonin. Thyroglobulin immunoreactivity was found in 4/20 tumors, 2 of them with classic and 2 with glandular histomorphological picture only in the cytoplasm of tumor cells. These tumors are considered medullary carcinomas with thyroglobulin immunoreactivity, since they do not fulfil the WHO criteria for "mixed medullary-follicular carcinomas".     

Sacral chordoma in early childhood: clinicopathological and immunohistochemical study

Two cases of sacral chordoma in a 7-year, 9-month-old boy and a 3-year, 4-month-old boy are presented. In addition to the typical histology of conventional chordoma, both tumors showed the less differentiated sarcomatoid appearance of atypical chordoma in the major portion. Immunohistochemically, in both cases neoplastic cells in areas of conventional as well as atypical chordoma were positive for keratins (CAM 5.2, AE1 and AE3), epithelial membrane antigen, vimentin, S-100 protein, carcinoembryonic antigen, and glial fibrillary acidic protein. Both patients underwent resection of the tumor and chemotherapy. In comparison with conventional chordomas in adults, however, these two tumors showed more aggressive clinical course and were less amenable to therapeutic control. The older boy died of multiple metastasis 1 year after initial diagnosis. At the last follow-up, 15 months after initial diagnosis, the younger boy was alive, but with recurrent and metastatic disease of the left parasacral area and chest wall. Our studies of these two cases and the reported cases suggest that sacral chordoma in children has distinctive clinicopathologic features denoting a highly aggressive tumor and that it should be treated as such.     

Small advanced colorectal adenocarcinomas: report on three cases

Small advanced cancers (less than 10 mm in size) have rarely been described in the literature, mainly due to their difficult endoscopic diagnosis. A total of 5120 colonoscopic examinations were performed at the National Cancer Center Hospital East; three cases (0.05%) of small advanced cancer were found. The indigo carmine dye spraying technique with magnifying endoscopy was used for diagnosis. All cases were flat and depressed lesions (8, 9 and 9 mm in size respectively) with V type pit pattern at the magnifying observation. Histology showed three cancers with invasion to the proper muscle layer and two cases of lymph node metastasis. K-ras point mutation was negative in all cases, while p53 stained in two out of the three cases (one diffuse and one focal). It is concluded that small advanced colorectal adenocarcinomas are a reality. Our data on their macroscopic appearance and histology confirm their high malignant potential.     

bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: association with clinical outcome

The bcl-2 proto-oncogene and the p53 tumor suppressor gene are important determinants of tumor cell susceptibility to apoptosis. bcl-2 and mutant p53 proteins inhibit apoptosis in vitro and can provide prognostic information in certain tumor types. We analyzed bcl-2 and p53 expression in archival pancreatic (n = 35) and ampullary (n = 6) adenocarcinomas, resected for cure, and their relationship to overall survival. Patients were treated with 5-fluorouracil and irradiation either pre- (n = 21) or postoperatively (n = 15); 5 patients received surgery alone. Using specific monoclonal antibodies, cytoplasmic bcl-2 and nuclear p53 proteins were detected in 22 of 40 (55%) and 20 of 37 (54%) tumors, respectively. No relationship was found between bcl-2 and p53 expression. Neither bcl-2 nor p53 correlated with histological response to preoperative chemoradiation. Lymph node involvement predicted poor overall survival (P = 0.02). A trend toward improved survival was seen in well-differentiated (P = 0.08) tumors and in those with increased bcl-2 expression (P = 0.06). p53 expression was not related to clinical outcome. In a multivariate analysis, nodal status was the single most important predictor of overall survival. Of note, the combined variable of bcl-2 expression and histological grade was a stronger prognostic variable than nodal status alone. Unlike nodal status, these features can potentially be evaluated in preoperative biopsy specimens.     

Extrahepatic peribiliary glands express alpha-amylase isozymes, trypsin and pancreatic lipase: an immunohistochemical analysis

We examined expression of alpha-amylase isozymes (pancreatic and salivary), trypsin and pancreatic lipase on the epithelium of extrahepatic peribiliary glands immunohistochemically using 53 autopsied normal extrahepatic bile ducts. Three parts of the extrahepatic bile duct (common bile duct, intrapancreatic bile duct and bile duct at the ampulla of Vater) were examined in each case. Histologically, the extrahepatic bile duct harbored branched tubular glands (extrahepatic peribiliary glands). Extrahepatic peribiliary glands were few in the common bile duct and intrapancreatic bile duct and numerous in the bile duct at the ampulla of Vater. Immunohistochemically, pancreatic alpha-amylase was expressed in the epithelium of extrahepatic peribiliary glands in 42 cases (79%). Salivary alpha-amylase was expressed in the epithelium of the glands in 38 cases (72%). Trypsin was expressed in the epithelium of the glands in 32 cases (60%). Pancreatic lipase was expressed in the epithelium of the glands in 45 cases (85%). The immunoreactivity of these enzymes was granular and located in the supranuclear cytoplasm (corresponding to the Golgi apparatus) of the epithelium of the glands. We confirmed the specificity of the immunoreactivity of these enzymes with various methods. These results suggest that extrahepatic peribiliary glands produce alpha-amylase isozymes, trypsin and pancreatic lipase and secrete these enzymes into lumens of the extrahepatic bile duct. The secreted enzymes may play an important role in the physiology of the extrahepatic bile duct and bile.     

Intradermal and subcutaneous leiomyosarcoma: a clinicopathological and immunohistochemical study of 41 cases

Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis. A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty-four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow-up information was available. Mean follow-up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases. Our study confirms that "pure" intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size > or = 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent prognostic factor.     

Localization of glycosaminoglycans (GAGs) in pleomorphic adenoma (PA) of salivary glands: an immunohistochemical and histochemical evaluation

The tumor matrix of salivary pleomorphic adenoma (PA) is characteristically rich in glycosaminoglycans (GAGs), which contribute to its complex histoarchitecture. This study evaluated the microscopic localization of various GAGs in 17 PAs, using a panel of anti-GAG monoclonal antibodies and biotinylated hyaluronic acid (HA)-binding protein. Both epithelial and mesenchymal-like tissues were confirmed to contain GAGs. Luminal epithelial cells mostly lacked GAGs, whereas GAGs were seen both in the cytoplasm and cell membrane of non-luminal epithelial cells. In addition, small intercellular accumulations of GAGs were often present in solid epithelial areas, implying the epithelial origin of GAGs. GAGs did not appear to be a main component of the hyaline matrix. The myxoid region was consistently stained for both chondroitin 6-sulfate (CS-6) and HA but variably for chondroitin 4-sulfate (CS-4), dermatan sulfate (DS) and keratan sulfate (KS); heparan sulfate (HS) was not detected. The chondroid region showed increased staining for CS-6 but reduced staining for HA when compared with the myxoid region. In addition, CS-4, DS and KS were seen both in chondroid cells and the territorial matrix, whereas HS was present only in the cells. It is suggested that GAGs in PA are mainly produced by non-luminal cells and influence the proliferation, differentiation, secretory activity and shape of tumor cells, thus contributing to the morphological diversity of this tumor.     

Small cell carcinoma of the uterine cervix: a clinicopathological review

Small cell carcinoma of the cervix is rare, with an aggressive natural history. We report on a series of 11 patients treated at the Christie Hospital, Manchester and examine their treatment and survival. Eleven patients with small cell carcinoma of the cervix were identified retrospectively from patient case notes. Treatment was individualised and included a variety of combinations of surgery radiotherapy and chemotherapy. Four patients were disease-free between 21 and 108 months (crude disease-free survival 36%). They presented with earlier disease and were older than the average for the group. They were all initially treated with radical radiotherapy. 7 patients died between 7 and 25 months. Despite combination chemotherapy, survival with advanced disease was poor. Published studies are small and fail to provide definitive answers on the best management of small cell carcinoma of the cervix. Drawing on the experience of small cell carcinoma of the lung however, combination therapy with radiotherapy, chemotherapy and possibly surgery requires careful assessment by an oncologist.     

Apoptosis in human gastric polyps and adenocarcinomas: a stereological analysis

BACKGROUND/AIM: The occurrence of apoptotic cells was analyzed in human normal gastric mucosa, polyps and adenocarcinomas. METHODOLOGY: Histological classification was carried out on hematoxylin and eosin stained slides. The tissue was classified as follows: Normal gastric mucosa or adenomatous polyps. Gastric carcinoma specimens were histologically classified according to Lauren's classification into: A: Diffuse adenocarcinoma without metastasis, B: Diffuse adenocarcinoma with metastasis, C: Intestinal adenocarcinoma without metastasis, D: Intestinal adenocarcinoma with metastasis, E: Mixed adenocarcinoma without metastasis and mixed adenocarcinoma with metastasis. The counting of apoptotic cells was performed using the 40X objective with a calibrated eyepiece Weibel's multi-purpose M 42 stereological test system. Each group was evaluated stereologically, determining numeric density of apoptotic cells. RESULTS: The results show the progressive and statistically significant increase of apoptotic numeric densities from normal gastric epithelium to adenomatous polyp and finally to cancer, which contained the highest number of apoptotic cells. Comparing gastric carcinoma with and without metastasis in intestinal and diffuse adenocarcinoma there was statistically significant difference. In these two groups, carcinomas with metastasis contained higher number of apoptotic cells than without metastasis. Gastric cancer according to numeric densities of apoptotic cells can be separated in tree statistically different groups: A: Intestinal type gastric cancer with metastasis (the highest number of apoptotic cells), B: Intestinal type gastric cancer without metastasis and diffuse gastric cancer with metastasis (medium number), C: Diffuse type gastric cancer without metastasis, mixed gastric cancer with and without metastasis (the lowest number of apoptotic cells). CONCLUSION: These results suggest that numeric densities of apoptotic cells are associated with tumor progression in human gastric carcinogenesis and can be used as prognostic mark.     

Ocular sebaceous carcinoma. Two unusual cases, and their histochemical and immunohistochemical findings

BACKGROUND: Since sebaceous carcinomas with a poor prognosis arising from the cutaneous adnexae of the eyelid are sometimes difficult to differentiate from squamous cell carcinoma or basal cell carcinoma on clinical and histopathological findings, definite differentiation between these tumors by additional methods is necessary. OBJECTIVE AND METHODS: To clarify the usefulness of histochemical and immunohistochemical examinations in diagnosing ocular sebaceous carcinoma, histochemical and immunohistochemical studies were carried out on the 2 patients with unusual ocular sebaceous carcinoma. RESULTS: The findings of ocular sebaceous carcinoma, at least in our 2 cases, were almost identical to those of extraocular sebaceous carcinoma. CONCLUSION: Immunohistochemical detection of human milk fat globules subclass 1, human milk fat globules subclass 2, and breast carcinoma-associated antigen 225 was useful for diagnosing ocular sebaceous carcinomas as well as extraocular ones.     

Frequent loss of p16 expression and its correlation with clinicopathological parameters in pancreatic carcinoma

Expression of the p16 gene product in human primary pancreatic carcinoma (PC) was investigated in paraffin-embedded tissue using a monoclonal antibody against p16 protein, clone G175-405, by means of immunohistochemistry, and the correlation of results with various clinicopathological parameters was evaluated. All six cases of normal pancreas and all but 1 of 20 cases of chronic pancreatitis expressed p16 protein, whereas 37.5% (3 of 8) of cystadenomas and 41. 9% (26 of 62) of PCs lost p16 expression. There was a significant difference between chronic pancreatitis and PC for frequency of the loss of p16 expression (P < 0.01). Moreover, loss of p16 expression in pancreatic malignancy was significantly associated with histological grade (G1 versus G2 and G3, P < 0.01) but not with sex, age, clinical stage, tumor location, or resectability. The survival period was shorter and metastasis is more likely in those cases that did not show p16 expression than those that did.     

Histologic and biologic patterns of microscopic pancreatic ductal adenocarcinomas detected incidentally at autopsy

BACKGROUND: The major clinical problems with pancreatic carcinoma are its silent course and late, fatal clinical manifestation. The results of treatments of small pancreatic carcinomas (<2 cm in greatest dimension) have led to the assumption that the detection of these cancers at earlier stages would lead to better survival and possible cure. Currently, there is no information about the histologic and biologic patterns of early stage pancreatic carcinoma, and the available data on incidentally detected tumors are fragmentary. The authors observed two incidental microscopic pancreatic ductal adenocarcinomas in female patients who died of advanced gastric carcinoma (Case 1) and renal carcinoma (Case 2). METHODS: The pancreatic lesions were examined histologically in serial sections and immunocytochemically for islet cells. Microdissection was performed so that the lesions could be examined for c-Ki-ras mutation. RESULTS: In Case 1, the pancreatic lesion was composed of cystic and solid components. The cystic component consisted of four small cysts compatible with a mucinous cystic tumor and showed no invasion. The solid component was a well-differentiated adenocarcinoma that occupied a 4 x 2 mm area. In Case 2, the pancreatic lesion contained two small, separate cysts, one of which was surrounded by two apparently separate, invasive adenocarcinomas 2.6 x 0.7 mm and 1.2 x 0.5 mm in greatest dimension. There was invasion of pancreatic islets and perineural spaces in both cases; and in Case 2, there was invasion of peripancreatic fatty tissue. In both cases, the epithelia of the cystic components and tumors showed mutation of the c-Ki-ras oncogene at codon 12, with GGT-to-GAT transition. CONCLUSIONS. Pancreatic carcinoma seems to occur under occult circumstances and maintain a silent course. Even in its early developmental stage, the cancer is invasive, primarily affects islets and nerves, and exhibits mutation of the c-Ki-ras oncogene. These findings call for urgency in the development of preventive modalities.     

Small bowel obstruction: sonographic evaluation

Results of 54 sonographic examinations of patients referred for suspected or known small intestinal obstruction were retrospectively correlated with surgical findings, and the diagnostic value of sonography regarding presence, level, and cause of obstruction was compared with that of plain abdominal radiography. The diagnosis of obstruction was correct in 89% of cases with sonography and in 71% with plain radiography. The level of obstruction was correctly predicted in 76% of cases with sonography and in 51% with plain radiography. The cause of obstruction was correctly predicted in 20% of cases with sonography and in 2% with plain radiography. The authors conclude that use of sonography in evaluating patients with bowel obstruction may be helpful in confirmation of the presence of obstruction, in determination of the level of obstruction, and in identification of the cause of obstruction.     

Adenosquamous carcinoma of the tongue: report of a case with histochemical, immunohistochemical, and ultrastructural study and review of the literature

The histologic examination of dental implants retrieved from humans is important to establish the causal determinants of implant failure, and to compare and validate the results obtained from animal studies. This study presents a retrospective review of the histologic features of 230 implants retrieved in an 8-year period (1989-1996). All the implants were treated to obtain thin (20 to 30 microm) ground sections. The majority of implants were retrieved because of mobility (n=56), peri-implantitis (n=54), or fractures (n=90). Peri-implantitis occurred more frequently before (n=44) than after (n=10) abutment connection. A dense fibrous connective tissue with no inflammatory cells was present at the interface in the implants retrieved for mobility; bone was found only in the most apical part. In many of these implants epithelial cells were present. The main histologic features of peri-implantitis consisted of the presence of a bone sequestrum near the implant, many bacteria present on the implant surface, and an inflammatory infiltrate (macrophages, lymphocytes, and plasma-cells) nearby. Histology showed that in the implants removed for fracture, there was a very high percentage (80 to 100%) of peri-implant bone.     

Cytochrome oxidase in Alzheimer's disease: biochemical, histochemical, and immunohistochemical analyses of the visual and other systems

Defects in oxidative metabolism have been implicated in Alzheimer's disease (AD). The present study evaluated the level of cytochrome oxidase (C.O.), an indicator of neuronal oxidative capacity, in various brain regions of post-mortem AD and control patients. We found a statistically significant reduction in C.O. levels in all cortical areas examined, including the primary and secondary visual cortices. In addition, all layers of the dorsal lateral geniculate nucleus and sublaminae of the primary visual cortex in AD cases examined suffered a reduction in their relative C.O. activity and protein amount. Our results suggest a generalized suppression of oxidative metabolism throughout the cortex, as well as in a major subcortical visual center in AD. Such hypometabolism may form the basis for not only deficits in higher cortical functions, but also a variety of visual dysfunctions known to occur in AD.     

Rickets in adult cystic fibrosis with myopathy, pancreatic insufficiency and proximal renal tubular dysfunction

Rickets is reported in a 19 year old white man with cystic fibrosis in whom pancreatic and hepatic involvement was advanced. There was evidence of secondary hyperparathyroidism with proximal renal tubular acidosis, aminoaciduria, phosphaturia and hypophosphatemia. Treatment with oral pancreatic and parenteral vitamin D supplements led to full recovery of the rachitic syndrome and the proximal renal tubular dysfunction.     

Mutation in the prion protein gene at codon 232 in Japanese patients with Creutzfeldt-Jakob disease: a clinicopathological, immunohistochemical and transmission study

The societal and economic forces driving change in medical education are affecting communities as well as universities. Each of the four authors of this paper is deeply involved in one of the components of their locale's well-developed community-based medical educational system, and each describes how change is influencing his role in that system, whether the role be managing a community hospital, directing a local Area Health Education Center, participating as a family medicine faculty member, or being a community preceptor. They agree on some common themes: (1) that it is good that medical students' education is moving into the community (e.g., this validates the importance of the community hospital to medical education, is an acknowledgment of the importance of generalism, and provides students invaluable learning experiences); (2) that educating medical students in the community is expensive, and more funding and resources are needed so that the area's hospitals, community faculty, preceptors, and support services can be fairly compensated for their commitment; and (3) that their community-based education system can no longer absorb the costs of training more medical students. This is not a criticism of academic medical centers, which are under tremendous financial pressures themselves, but is simply to state the community perspective and to urge fairness in the distribution of resources for medical education. Community institutions and academic medical centers will work individually to create their own integrated health care systems but must work together to create a better, more cost-effective system for educating medical students.     

A histochemical and immunohistochemical study of certain defense mechanisms in the human lacrimal sac epithelium

The mucosal surface of the human lacrimal sac represents an area exposed to exogenous agents including potentially harmful microorganisms. The human lacrimal sac was examined histochemically to identify glycoproteins, and immunohistochemically to identify secretory IgA. Neutral and acid glycoconjugates were detected mainly in the cytoplasm of the surface cells of the columnar stratified epithelial lining. The same reactions were recognized in occasional clusters of secretory cells forming intraepithelial glands in the lining of the lacrimal sac. The presence of secretory IgA in the cytoplasm of the apical epithelial cells was demonstrated. The results indicate that the lacrimal sac mucosa possesses certain active defense mechanisms against ascending infections.