Early-onset diabetes mellitus as a presenting feature of Werner's syndrome in an Indian family.

Background: Diabetes mellitus (DM) in children and adolescents is typically caused by type 1 DM, followed by type 2 DM and maturity-onset diabetes of the young (MODY). We report an unusual Asian Indian family in which three members presented with DM at ages 15, 20, and 30, but not fitting the typical clinical picture of type 1 DM, type 2 DM, or MODY. The primary objective was to elucidate the molecular genetic basis of DM in this family.

Multisystem Progeroid Syndrome With Lipodystrophy, Cardiomyopathy, and Nephropathy Due to an p.R349W Variant.

Background: Pathogenic variants in lamin A/C () cause a variety of progeroid disorders including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and atypical progeroid syndrome. Six families with 11 patients harboring a pathogenic heterozygous c.1045C>T; p.

Postmortem Findings in a Young Man With Congenital Generalized Lipodystrophy, Type 4 Due to CAVIN1 Mutations.

Context: Congenital generalized lipodystrophy, type 4 (CGL4) is a rare autosomal recessive disorder caused by mutations in caveolae-associated protein 1. Patients with CGL4 also have myopathy and cardiomyopathy with a predisposition for sudden death due to ventricular arrhythmias. However, the underlying pathology for these morbidities remains unknown.

Congenital dermoid cyst of the middle ear.

Dermoid cysts of the head and neck are rare lesions comprised of epidermal and mesodermal elements. We report a dermoid cyst presenting in the middle ear of the youngest patient reported to date. Structures of endodermal descent were also identified, but, given that the entire middle ear mucosa is of endodermal origin, specific classification as a teratoma would be imprecise.

Post-mortem findings in familial partial lipodystrophy, Dunnigan variety.

Aims: Familial partial lipodystrophy, Dunnigan variety (FPLD), is an autosomal dominant disorder due to missense mutations in the lamin A/C gene and is characterized by gradual loss of subcutaneous fat from the extremities and trunk, fat accumulation in the head, neck and intra-abdominal areas, insulin resistance and its metabolic complications. We studied autopsy findings in two patients with FPLD to determine fat distribution and organ involvement.

Results: Patient 1, a 66-year-old woman with the R482Q mutation, had diabetes mellitus, dyslipidaemia, and coronary artery disease and died suddenly.

Hyalinizing clear-cell carcinoma of salivary glands in fine-needle aspiration.

Hyalinizing clear-cell carcinoma (HCCC) is a recently described distinctive salivary gland neoplasm. Because of its cytoplasmic clearing and the bland nuclear features, HCCC resembles other tumors. The authors describe the cytomorphologic features of four cases of HCCC in fine-needle aspirates (FNA) and discuss the differential diagnosis.

Fine-needle aspiration findings in Castleman's disease.

Castleman's disease of the hyaline vascular subtype is an uncommon lesion; experience with fine-needle aspiration (FNA) of this tumor is limited to rare case reports. We describe the cytologic, flow cytometric, and immunohistochemical findings in two cases initially sampled by FNA. Two females, aged 40 and 26 yr, were found incidentally to have an oropharyngeal and a mediastinal mass, respectively.

Fine-needle aspiration findings in patients with polymorphous low grade adenocarcinoma of the salivary glands.

Background: Polymorphous low grade adenocarcinoma of the salivary glands (PLAC) is a low grade neoplasm that predominantly occurs in the minor salivary glands. In this site it is amenable to biopsy and histologic diagnosis. However, experience with fine-needle aspiration (FNA) biopsy findings in these tumors is limited.

Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: a histopathologic and immunohistochemical comparison.

Because of histological similarities between nephrogenic adenomas and clear cell adenocarcinomas of the urinary tract, there is the potential for diagnostic confusion between these two entities. The histopathologic features of 13 nephrogenic adenomas and five clear cell adenocarcinomas of the urethra and urinary bladder are compared in this report, and detailed immunohistochemical staining profiles are provided for these tumors. Only 2 of the 13 nephrogenic adenomas contained clear cells, and these constituted less than 10% of the lesions.

Deoxyribonucleic acid flow cytometry and traditional pathologic variables in invasive penile carcinoma: assessment of prognostic significance.

Objectives: The identification of reliable prognostic factors to guide the selection of patients at high risk of harboring subclinical metastases in penile cancer is important. We evaluated traditional pathologic variables and deoxyribonucleic acid (DNA) flow cytometry to determine the prognostic significance of these variables for the subsequent development of lymph node metastases.

Methods: Clinical data and pathologic specimens were retrospectively reviewed from patients treated surgically at university-affiliated hospitals from 1958 to 1987.

DNA analysis at p53 locus in adenoid cystic carcinoma: comparison of molecular study and p53 immunostaining.

Abnormalities of the p53 tumor suppressor gene were investigated in 22 foci from 14 adenoid cystic carcinomas (ACC) by polymerase chain reaction (PCR)-based assays for dinucleotide (CA)n and pentanucleotide (AAAAT)n repeat polymorphisms and by immunohistochemical staining for oncoprotein expression. Adenoid cystic carcinomas were divided into lower grade (tubular and cribriform) subtypes and higher grade (trabecular and solid) subtypes. Histologically identified tumor cells were precisely microdissected from archival microslides and were used for molecular analysis.

DNA analysis at p53 locus in carcinomas arising from pleomorphic adenomas of salivary glands: comparison of molecular study and p53 immunostaining.

Where and how frequently p53 abnormalities are involved in the development of pleomorphic adenoma (PA) and its malignant progression to carcinoma was investigated. The presence of p53 gene abnormalities was analyzed in eight patients with carcinoma in pleomorphic adenoma (CPA) by polymerase chain reaction (PCR)-based assays and immunohistochemistry. Normal salivary gland tissue, adenomatous, transitional and carcinomatous areas were microdissected from archival microslides and analyzed for allelic deletions of the p53 gene using two microsatellite markers at the p53 locus; dinucleotide (CA)n repeat and pentanucleotide (AAAAT)n repeat.

Seven-week continuous-infusion paclitaxel with concurrent radiotherapy for locally advanced head and neck squamous cell cancer: a phase I study.

The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7-week total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with standard curative radiotherapy (RT) for previously untreated, locally advanced head and neck squamous cell cancers. Eligible patients have squamous cell cancers of the head and neck with expected 5-year survival rates of < or =25%; a good performance status; adequate hematologic, hepatic, and renal functions; and no distant metastases. All patients receive 70 Gy megavoltage RT in 7 weeks (2 Gy/d x 5 d/wk).

Telomerase activity in benign and malignant thyroid diseases.

Background: Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant cells and is inactive in most normal somatic cells, with the excitation of proliferative stem cells, male germ cells, and activated lymphocytes. The measurement of telomerase activity in clinically obtained tissue samples may provide useful information as both a diagnostic and prognostic marker. In this study, we sought to determine whether telomerase activity might prove helpful in the assessment of benign and malignant thyroid tumors.

Macrofollicular variant of papillary thyroid carcinoma with minor insular component.

Background: The macrofollicular variant of papillary thyroid carcinoma that is the subject of this study has only recently been characterized. Information about its morphologic spectrum and biologic behavior is limited.

Methods: The authors reviewed 29 examples, including 17 previously reported cases.

Seven-week continuous-infusion paclitaxel plus concurrent radiation therapy for locally advanced non-small cell lung cancer: a phase I study.

The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when combined with standard, curative-intent radiation therapy (RT) for previously untreated, locally advanced non-small cell lung cancers. Eligible patients have locally advanced (T4NXM0 or TXN2-3M0) non-small cell cancer ineligible for potentially curative surgical resection, a good performance status, adequate hematologic, hepatic, and renal functions, and no distant metastases. All patients receive a total tumor dose of 64.

Intensive radiation therapy concurrent with up to 7-week continuous-infusion paclitaxel for locally advanced solid tumors: phase I studies.

Patients with locally advanced solid tumors of the lung, head and neck, and malignant astrocytomas usually succumb to their disease despite aggressive standard therapy. Laboratory data suggest that the addition of 1.0 to 10 nmol/L paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a microtubule stabilizing drug, to radiation therapy may result in significant radiation sensitization, perhaps due to accumulation of cells at G2/M.

Computed tomography and magnetic resonance diagnosis of allergic fungal sinusitis.

The objective of this study was to describe CT and MR findings in patients with allergic fungal sinusitis (AFS). CT and MR images were examined from 10 patients with histologically proven AFS. All patients demonstrated CT evidence of central sinus high attenuation and T2-weighted MR signal void corresponding to surgically proven areas of thick inspissated allergic mucin.

Neuroendocrine tumors of the lung. Pathology and molecular biology.

Our understanding of the molecular genetic changes in lung cancer pathogenesis is advancing rapidly with several specific genes and chromosomal regions having been identified. As the biochemical functions of the proteins encoded by these genes are discovered, they appear to fall into several growth regulatory pathways. The large number of genetic lesions in clinically evident lung cancer has prompted searching for mutations in preneoplastic lung tissue before the pathologic evidence of cancer as a tool for early molecular diagnosis.

Middle ear mucocele: an unusual complication of the tranlabyrinthine approach to acoustic neuroma.

The complications of posterior fossa surgery continue to decrease in incidence as our collective experience broadens. Most complications are seen in the immediate postoperative period and the minimized by careful attentiveness to subtle changes in mental status, vital signs, and cranial nerve examination. Long-term follow-up is necessary to identify tumor recurrence, but strict imaging protocols as yet do not exist to facilitate the early identification of recurrent disease, as recurrence is very rare.

Loss of heterozygosity and microsatellite alterations in p53 and RB genes in adenoid cystic carcinoma of the salivary glands.

Adenoid cystic carcinomas (ACC) constitute approximately 20% of malignant salivary gland tumors. Several histological types of ACC are recognized and may coexist in a single tumor. The authors divided ACC into lower grade (tubular and cribriform subtypes) and higher grade (trabecular and solid) subtypes.

Mutations associated with carcinomas arising from pleomorphic adenomas of the salivary glands.

Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands. Carcinomas in pleomorphic adenomas (CPAs) may arise by malignant transformation of the epithelial components of PAs. Occasionally, transitional zones containing cells with histological features intermediate between those of the benign PA and carcinomatous components of CPA are identified.

Severe islet amyloidosis in congenital generalized lipodystrophy.

Objective: Islet amyloidosis may be one mechanism for pancreatic islet beta-cell loss that is associated with the development of NIDDM. However, the question remains whether chronic overstimulation of insulin and islet amyloid polypeptide (IAPP) secretion in states of insulin resistance could lead to formation of islet amyloidosis and hence NIDDM in some patients. We studied pancreatic islet pathology in congenital generalized lipodystrophy, a genetic syndrome of extreme insulin resistance that may provide some clues.

Extensive areas of aneuploidy are present in the respiratory epithelium of lung cancer patients.

According to the field cancerisation theory the entire upper aerodigestive tract has been mutagenised, thereby placing the affected individual at risk for the development of one or more cancers. To investigate this concept we studied the respiratory epithelium in lungs bearing cancer, including bronchi, bronchioles and alveoli. After identifying preneoplastic and preinvasive lesions by light microscopy, we determined the DNA content of their nuclei in Feulgen-stained sections using a high-performance digitised image analyser.