Detection of messenger RNA from O6-methylguanine-DNA methyltransferase gene MGMT in human normal and tumor tissues.

BACKGROUND: The level of the DNA repair protein O6-methylguanine-DNA methyltransferase is an important determinant of the response of tumor cells in culture to alkylating nitrosoureas. In these cells, the abundance of messenger RNA (mRNA) is directly correlated with repair activity. PURPOSE: Our purpose was to compare transferase mRNA levels with the repair activity in primary human tumors. METHODS: Human transferase mRNA was measured in tissue samples from brain tumors, normal lung, lung tumors, ovarian tumors, and normal human liver by use of an RNA protection assay with an antisense probe prepared from the cloned gene. RESULTS: Normal and tumor tissue samples from the same patient had similar transferase activity levels, but transferase expression varied widely among tissue samples from different patients. Brain and lung samples, on average, had transferase mRNA levels closer to those in liver samples than their transferase activity levels. In two cases, tissue samples which were transferase deficient by the activity assays were found to lack transferase mRNA. CONCLUSIONS: Deficiencies in transferase activity are due to reduced or absent mRNA transcription or processing. In brain and lung, there may be post-transcriptional control of mRNA expression. The wide interindividual variation in transferase expression is also seen at the transcription level. IMPLICATIONS: These are among the first measures of transferase mRNA expression in primary human tissue. More samples should be examined to extend these observations.

O6-methylguanine-DNA methyltransferase in human normal and tumor tissue from brain, lung, and ovary.

The resistance of human tumor strains in culture to cell killing by alkylating nitrosoureas is correlated with their levels of the DNA repair activity O6-methylguanine-DNA methyltransferase. Strains with the Mer- phenotype have no activity and are extremely sensitive. However, the relationship between the sensitivity of human tumors in vivo and transferase levels is not known, and even the existence of Mer- human tumors in vivo has been questioned. In this study 73 human tumor and normal tissue samples from brain, lung, and ovary were assayed for transferase levels and methylpurine glycosylase activity. For each organ, transferase levels varied over 100-fold, and Mer- tumors were detected in each group. There was no correlation between transferase and glycosylase levels, indicating that the absence of transferase in some tumor samples was not an artifact due to necrosis or inactivation of enzymes in the extract.

Accuracy of reported family history of diabetes mellitus. Results from San Luis Valley Diabetes Study.

There are two possible sources of bias in the assessment of family history of diabetes: 1) a person with diabetes may be more likely to report a diabetic relative than a nondiabetic person would be, and 2) relatives of individuals with diabetes may be more likely to be tested for diabetes than relatives of nondiabetic individuals. We conducted a study on a subsample of families of subjects in the San Luis Valley Diabetes Study to examine these issues. A sample of 5 White and 5 Hispanic subjects (probands) with diabetic glucose tolerance tests and the same number with normal glucose tolerance were selected. The 20 probands all provided contact information on their 227 primary family members. Ninety-two percent of the family members had interviews completed by themselves or, if deceased, by surrogates other than the proband. Family members were asked by telephone if they had ever been tested for diabetes, when they had been most recently tested, why they had been tested, and if they had ever been told they had diabetes. The results showed that study subjects accurately reported family history of diabetes, because there were no discrepancies between proband and family reports. A positive family history of diabetes was associated with increased reported screening in Hispanics, but a similar effect in White families was not seen. Women were also more likely to report being screened than men regardless of whether there was a positive family history of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Microvascular complications of NIDDM in Hispanics and non-Hispanic whites. San Luis Valley Diabetes Study.

The goal of this article was to examine the differences in the rates of microvascular complications of non-insulin-dependent diabetes mellitus (NIDDM) in Hispanic and non-Hispanic white subjects. This was a geographically based case-control study where prevalent cases of NIDDM were identified in medical records. Subjects attended a 4-h clinic to confirm NIDDM diagnosis and assess complication end points. Retinopathy was defined by stereofundus photographs. Distal symmetric neuropathy was determined by standardized clinical examination. Nephropathy was indicated by serum creatinine level, urine protein-creatinine ratio, and urine albumin concentration. This study consisted of 279 NIDDM subjects confirmed by oral glucose tolerance test and World Health Organization criteria aged 20-74 yr (187 Hispanic and 92 non-Hispanic white subjects). Duration-adjusted prevalence of retinopathy was significantly higher in non-Hispanic white subjects (54.1 per 100, 95% confidence interval [CI] 44.4-63.7) than in Hispanics (41.8 per 100, 95% CI 34.8-48.8). This excess occurred only in non-Hispanic white subjects with background retinopathy but not in those with more severe retinopathy. Hispanics and non-Hispanic white subjects did not differ significantly for the prevalence of neuropathy (31.6 per 100 in non-Hispanic white subjects and 26.3 per 100 in Hispanics) or nephropathy by any measure. There were no significant differences in duration of diabetes or mean glycohemoglobin levels between ethnic groups. Microvascular complications of NIDDM are not in excess among Colorado Hispanics, and retinopathy may be somewhat more common in non-Hispanic white people.

Amyloid tumor. A clinicopathologic study of four cases.

Four examples of amyloid tumors were studied to determine whether there was an association with myelomatosis. Three patients had follow-up examinations of 12 years, 9 years, and 2 1/2 years, respectively. A local recurrence developed in one patient and a second lesion developed in this patient and in one other who also had a transient monoclonal 7S globulin peak. In spite of these findings, none of our patients developed myelomatosis. A study of the scanty literature on amyloid tumors reveals that only patients with lesions of the lung and urinary bladder have had long-term follow-up. They have invariably remained free of disease. Several reports of bone lesions have inferred that amyloid tumors occurring here signify solitary myeloma despite a lack of follow-up confirmation. Our longest surviving patient developed two bone lesions over a 12-year period without developing myelomatosis. Our findings lead us to conclude that there is little evidence to regard the presence of an amyloid tumor at any site as a manifestation of solitary myeloma or myelomatosis.

Chondroid chordoma. Electron-microscopic study of two cases.

Chondroid chordoma is an unusual tumor composed of an admixture of chondromatous and chordomatous tissue usually located in the spheno-occipital region. This tumor shares many of the clinical and histologic features of classic chordoma and chondrosarcoma and has been shown to have a better prognosis than either of these lesions. To the best of our knowledge, no ultrastructural studies have been performed in the 26 cases of chondroid chordoma published previously. We document the ultrastructural features of two examples of chondroid chordoma. Certain features such as prominent and dilated rough endoplasmic reticulum, intracytoplasmic glycogen aggregates, and abundant fibrillogranular matrix are common to chordoma, chondrosarcoma, and chondroid chordoma. The presence of well-formed tonofilament desmosome complexes as well as complexes composed of alternating profiles of rough endoplasmic reticulum and mitochondria were seen only in chordoma and chondroid chordoma, but not in cartilaginous tumors. Of particular interest was the finding of crystalline, tubular structures within the rough endoplasmic reticulum of both cases of chondroid chordoma, a finding not described previously. The distinction of chondroid chordoma from classical chordoma is said to be a difficult one at the light-microscopic level, and we suggest that these intraergastoplasmic tubular structures might constitute an extremely helpful differential marker.

Chronic granulomatous disease of childhood presenting as gastric outlet obstruction.

A case of chronic granulomatous disease of childhood was first diagnosed when a 20-month-old infant developed gastric outlet obstruction. Because of the unusual clinical presentation and negative gastric mucosal biopsies, the diagnosis was delayed. A subsequent full thickness biopsy of the stomach wall which led to a correct diagnosis showed a granulomatous infiltrate in the muscularis propria. Characteristic yellow pigment-laden macrophages were seen in the gastric mucosa and pyloric lymph node. Early recognition of this chronic disorder is important not only for proper management but genetic counseling as well.

Benign lymphoepithelial lesion (Mikulicz's disease) of the salivary gland: an ultrastructural study.

An ultrastructural study of a benign lymphoepithelial lesion of the parotid gland demonstrated that the so-called epimyoepithelial cell islands were sharply demarcated from the surrounding parenchyma by a thick basement membrane containing collagen fibers. The hyaline material seen by light microscopy within the islands was ultrastructurally similar in appearance to this delimiting basement membrane. The epithelial cells within the islands were united by well formed desmosomes and many had prominent tonofilament bundles, but myogenic differentiation was not observed. Hydropic degeneration was not seen in these epithelial cells; cells with a perinuclear clear space seen by light microscopy corresponded to large lymphoid cells ultrastructurally.

Myofibroblasts and related cells in malignant fibrous and fibrohistiocytic tumors.

Myofibroblasts were detected by electron microscopy in five of five cases of fibrosarcoma and in five of six cases of malignant fibrous histiocytoma. In some areas myofibroblasts constituted up to 75 per cent of the tumor cells. Most myofibroblasts contained only sheaves of myofilaments along the margins of the cells, but some cells contained larger bundles of myofilaments and very closely resembled smooth muscle cells. An additional related type of cell was seen in several cases; it was large and possessed abundant eosinophilic cytoplasm, resembling a rhabdomyoblast at the light microscopic level. By electron microscopy this type of cell was seen to contain plentiful rough endoplasmic reticulum and large aggregates of fine filaments with rare dense bodies. These findings suggest that fibrosarcomas and malignant fibrous histiocytomas contain cells showing a spectrum of differentiation from fibrocytic to myogenic and that at the ultrastructural level the distinction between fibroblast and smooth muscle tumors may be blurred.

Multiple juvenile polyposis. A study of the pathogenesis of juvenile polyps and their relationship to colonic adenomas.

Solitary juvenile polyps are common lesions whose pathogenesis is poorly understood. Multiple juvenile polyposis is characterized by large numbers of these lesions either confined to the colon or throughout the gastrointestinal tract. A study of two cases of multiple juvenile polyposis provided fresh insight into the pathogenesis of juvenile polyps and their relationship to colonic adenomas. Mucosal ulceration in very early lesions, together with glandular epithelial calcification, suggested that impaired cell renewal resulting from disturbed regenerative kinetics may predispose to surface epithelial erosion, setting in motion a cycle of ulceration, inflammation, and granulation tissue formation. We postulate that a dyskinetic continuum may link juvenile, "metaplastic," and adenomatous polyps. The finding in our second case of multiple adenomatous lesions, including a villoglandular polyp, emphasizes the neoplastic potential of juvenile polyposis.

Simultaneous renal cell carcinoma and squamous cell carcinoma of kidney.

A unique case of a collision tumor of the kidney composed of a renal cell carcinoma and a squamous cell carcinoma is reported. Although a few cases of combined tumors of the kidney have been reported previously, we were unable to find any similar case in the literature. Squamous cell carcinoma of the kidney usually behaves aggressively. Early diagnosis and surgical treatment before the tumor has extended beyond the capsule offer the best hope of cure.

Dermatofibrosarcoma protuberans with lymph node and pulmonary metastases.

Dermatofibrosarcoma protuberans is a locally aggressive histiocytic tumor that, on rare occasions, may metastasize to regional lymph nodes or even to distant sites. We report a dermatofibrosarcoma protuberans with lymph node involvement in a 27-year-old woman. This tumor recurred repeatedly after local excisions, and ten years after the first resection, widespread pulmonary metastases developed in the patient and she died four years later. More than 400 patients with dermatofibrosarcoma protuberans have been reported in the literature; including the present case, five of these patients had lymph node metastases, 17 patients had hematogenous spread, and three had both lymphatic and blood-borne metastases.

Vocal cord polyps: biochemical and histologic evaluation.

The stratified squamous epithelium covering vocal cord polyps can vary from normal to hyperplastic and keratinized. We have analyzed the histology and cytokeratins of 11 of these polyps. Cytokeratins were separated on one-dimensional SDS-acrylamide gels to determine molecular weights. There was significant heterogeneity in the cytokeratins present in the different polyps. Comparison of histologic findings and cytokeratin content showed a correlation between extent of keratinization and presence of high molecular weight cytokeratins. We conclude that the epithelium of vocal cord polyps exhibit patterns of cytokeratins characteristic of both hyperproliferation and abnormal states of differentiation, which are mirrored by histologic variations, and that vocal cord polyps are a heterogeneous group of benign lesions.

So-called pseudosarcoma of the esophagus: nodal metastases of the spindle cell element.

A polypoid lesion of the esophagus with all the morphological features of a so-called pseudosarcoma produced nodal metastases of the spindle cell element. Ultrastructurally, these spindle cells showed only fibroblastic features. The findings in this case and a review of cases reported as pseudosarcoma of the esophagus lend little support for the contention that they differ from cases categorized as carcinosarcoma of the esophagus.

Superficial cystic gastritis with alopecia. A forme fruste of the Cronkhite-Canada syndrome.

The Cronkhite-Canada syndrome is a rare and often fatal condition. A case of superficial cystic gastritis was suspected on peroral gastric biopsy and was later confirmed at autopsy. The selective involvement of the stomach together with the presence of alopecia leads us to conclude that this case is unique and represents a forme fruste of the Cronkhite-Canada syndrome. A complicating feature was the presence of an opportunistic cytomegalovirus infection of the gastrointestinal tract and lungs.

Periosteal chondrosarcoma: a case report and review of the literature.

Periosteal chondrosarcoma occurs predominantly in the long tubular bones. The long-term survival rate is better and there are fewer local recurrences than with central chondrosarcoma. A case of periosteal chondrosarcoma is reported with a review of the literature. A 13-year-old girl presented with swelling of the distal right thigh of 3 weeks' duration. Radiographs and computed tomographic scan of the lesion showed a soft tissue mass, measuring 6 x 6 cm, with matrix calcification arising from the surface of the bone. An open biopsy followed by en bloc resection of the tumor was performed. The histologic features were those of a chondrosarcoma. An 8-year follow-up period has shown no local recurrence or distant metastases. The differential diagnosis of periosteal chondrosarcoma includes periosteal (chondroblastic) osteosarcoma and periosteal chondroma. Controversy exists as to whether periosteal chondrosarcoma is an entity distinct from periosteal osteosarcoma. The clinicopathologic features in this case and in the cases reported in the literature support the contention that periosteal chondrosarcoma is indeed distinct.

Sinus histiocytosis with massive lymphadenopathy and unusual extranodal manifestations.

We describe a predominant extranodal involvement of unusual sites by sinus histiocytosis with massive lymphadenopathy (SHML). The patient first presented at 13 years of age with bilateral parotid gland enlargement and was discovered to have a large asymptomatic left renal mass and adjacent hilar adenopathy, histologically diagnostic of SHML. Following a left nephrectomy, he remained well with persistent parotid and lacrimal gland disease and, 20 years later, plaquelike meningeal involvement mimicking meningioma en plaque developed that was associated with reactive meningeal nests within the body of the lesion. At no time during the last 20 years has there been a recurrence of significant external nodal enlargement, and biopsy specimens of neck and intrathoracic lymph nodes have been nondiagnostic of SHML.

Calcospherites in pituitary prolactinomas. A hypothesis for their formation.

Calcospherites are being reported with increasing frequency in pituitary prolactinomas. Ultrastructural study of such a case, along with the recent characterization of the molecular composition of prolactin granules, has led us to hypothesize that a unique intracellular milieu exists in which calcification can be initiated and can proceed to calcospherite formation.

Primary meningeal mesenchymal chondrosarcoma.

A primary meningeal mesenchymal chondrosarcoma initially resembled an angioblastic meningioma because the typical chondroid islands were not demonstrable. Cartilage was seen only in an intracerebral recurrence and in subsequent extracranial metastases. Ultrastructural examination of noncartilaginous regions of the tumor demonstrated mesenchymal cells with features suggestive of cartilaginous differentiation, viz, scalloped cell membranes, sac-like distension of abundant rough endoplasmic reticulum, and a matrix containing fibrillary and finely granular material. Features of meningeal or pericytic cells were not seen.

Crystal-storing histiocytosis associated with a lymphoplasmacytic neoplasm mimicking adult rhabdomyoma: a case report and review of the literature.

Massive accumulation of crystals within histiocytes in association with a lymphoplasmacytic neoplasm causing histologic features closely mimicking adult rhabdomyoma is a rare occurrence. We report the case of a 49-year-old man who presented with a left posterior cervical mass. Histologic examination demonstrated sheets of large, elongated, and polygonal cells with prominent eosinophilic cytoplasm surrounding scattered dense lymphoplasmacytic collections. Evidence of the reactive histiocytic nature of the eosinophilic cells was provided by an immunohistochemical reaction that was positive with KP-1 (CD68), but negative with common muscle actin, desmin, and myoglobin. The ultrastructural finding of elongated and rhomboid, membrane-bound, cytoplasmic crystals further supported the reactive histiocytic nature of these cells. B-cell kappa monoclonality of the lymphoplasmacytic component was proven by gene rearrangement studies. A recurrence involving the right parotid gland, 18 months after removal of the cervical mass, confirmed the aggressive nature of this B-cell lymphoma. Misdiagnosis of crystal-storing histiocytosis as adult rhabdomyoma can be avoided if the following features are recognized: lack of cytoplasmic cross striations, frequent multinucleation of the histiocytes, and prominence of the atypical lymphoplasmacytic component.