A newly recognized entity: intraductal "oncocytic" papillary neoplasm of the pancreas

Intraductal papillary-mucinous tumors of the pancreas are increasingly recognized, and their characteristic endoscopic and radiological features are well reported in the literature in recent years. Oncocytic features in these tumors are uncommon and unrecognized. Intraductal oncocytic papillary neoplasm is a distinct pancreatic tumor and is a recently recognized entity. We report a case of a 69-yr-old patient who presented with symptoms mimicking pancreatitis, resulting in delay in the diagnosis of her pancreatic tumor. She underwent a successful Whipple's procedure and subsequently has remained well. The resected specimen showed an intraductal oncocytic papillary-mucinous neoplasm. The entity is new and the literature information is inadequate at present to judge the biological behavior of this tumor. We discuss this recently recognized entity.     

Intraductal papillary tumors and mucinous cystic tumors of the pancreas: clinicopathologic study of 38 cases

Clinicopathological features of 28 patients with intraductal papillary tumor (IDPT) and 10 patients with mucinous cystic tumor (MCT) of the pancreas were studied. Both IDPT and MCT showed papillary projections of the epithelium with abundant mucus secretion in the ectatic ducts or cystic spaces. The patients with IDPT comprised 19 men and 9 women with a mean age of 64.9 years. Three fourths of the IDPTs were located in the pancreatic head, and the mean tumor size was 3.5 cm. Local recurrence was observed in one patient, but none died of IDPT. In contrast, all patients with MCT were women, with a mean age of 49.4 years. None of the MCTs arose in the head, and the mean tumor size was 7.1 cm. One patient died of MCT, but all of the others survived without recurrence. Eight IDPTs and three MCTs showed invasion into the surrounding pancreatic tissue. Muconodular infiltration was mainly observed in five IDPTs and one MCTs and tubular infiltration in three IDPTs and two MCTs. A characteristic histological finding associated with the muconodular infiltration in IDPT was subepithelial "mucin droplets" that appeared to represent a change in polarity of mucus secretion. The formation of such subepithelial "mucin droplets" may be the initial step of muconodular infiltration in IDPT. Muconodular infiltration in IDPT appears different morphologically and biologically from the mucinous carcinoma subtype of conventional invasive ductal carcinoma.     

Localized malignant mesothelioma. A clinicopathologic and flow cytometric study

Six examples of malignant mesothelioma appearing as a localized pleural mass are described. There were four women and two men, ranging in age from 42 to 76 years. A history of asbestos exposure was obtained from three patients. The tumors ranged in size from 2.8 to 10 cm. Two were pedunculated and four were sessile with broad-based pleural attachments. Histologically, three tumors were purely epithelioid and three were biphasic. Immunohistochemical stains in all six cases were positive for cytokeratin and negative for carcinoembryonic antigen. Five were also positive for epithelial membrane antigen. Five were negative for Leu-M1, while one showed focal staining in a peripheral membrane pattern. Electron microscopy in two purely epithelioid tumors showed long, thin microvilli, well-developed desmosomes, and numerous tonofilaments. Flow cytometry showed an aneuploid DNA content in four tumors and a diploid content in one. Flow cytometry in five cases identified a DNA aneuploid cell population in four tumors and a diploid population in one. Three patients showed signs of local recurrences 4, 7, and 18 months after excision and died of their disease 12, 10, and 24 months after diagnosis, respectively. Three patients are well with no evidence of disease 8, 24, and 96 months after diagnosis. These findings indicate that malignant mesotheliomas of the pleura may rarely appear as a localized mass. The biologic behavior of such tumors is difficult to predict, but some patients survive disease-free for a long time after surgical excision.     

A practical approach to breast ductal carcinoma in situ and tumors with an extensive intraductal component

Seventy-two patients were admitted in a multicentre trial with the purpose of assessing the clinical efficacy and safety of the hormonal control and tolerance of leuprolide acetate in a once-a-month depot injection formulation for the treatment of disseminated prostate cancer. During a 1-year follow-up, there were ten withdrawals for different reasons. At baseline and at 6 months of treatment the following parameters were evaluated: clinical examination, routine blood analysis, PAP, PSA, LH and testosterone, as well as bone scan. LH and testosterone determinations were repeated at 2, 4, 8, 12, 16, 20 and 24 weeks. Testosterone reached castration levels within the second week and was maintained until the end of the study. In agreement with the NPCP criteria, 65 patients were assessed as: complete response 3%, partial response 40%, disease stabilization 36%, and progression 21%. In summary, a once-a-month injection of leuprolide acetate offers a safe and effective alternative to surgical castration.     

Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome

Between July, 1984, and October, 1988, 263 patients (163 male, 100 female), aged from 4 to 83 years (mean 52 years), with malignant brain gliomas underwent surgical procedures: stereotactic biopsy in 160 and resection in 103 patients. There were 170 grade IV astrocytomas, 17 grade IV mixed oligoastrocytomas, 44 grade III astrocytomas, 22 grade III mixed oligoastrocytomas, and 10 malignant oligodendrogliomas. Overall median survival time was 30.1 weeks for grade IV gliomas, 87.7 weeks for grade III gliomas, and 171.3 weeks for malignant oligodendrogliomas. Multivariate analysis in 218 newly diagnosed cases revealed that the variables most strongly correlated with survival time were: tumor grade, patient age, seizures as a first symptom, a Karnofsky Performance Scale score of less than 70%, tumor resection, and a radiation therapy dose greater than 50 Gy. The proportions of patients receiving tumor resection versus biopsy in each of these prognosis factor groups were similar. Since most of the 22 patients with midline and brain-stem tumors were treated with biopsy alone, these were excluded. Considering 196 newly diagnosed patients with cortical and subcortical tumors, grade IV glioma patients undergoing resection of the contrast-enhancing mass (as evidenced on computerized tomography and magnetic resonance imaging) and postoperative external beam radiation therapy lived longer than those undergoing biopsy only and radiation therapy (median survival time 50.6 weeks and 33.0 weeks, respectively; Smirnov test, p = 0.0380). However, survival in patients with resected grade III gliomas was no better than in those with biopsied grade III lesions (p = 0.746). The authors conclude that, in selected grade IV gliomas, resection of the contrast-enhancing mass followed by radiation therapy is associated with longer survival times than radiation therapy after biopsy alone.     

Pulmonary alveolar microlithiasis. A clinicopathologic and chemical analysis of seven cases

OBJECTIVE: To examine the association of the molecular variants of the angiotensinogen (AGT) gene with essential hypertension in Taiwanese. METHODS: We conducted a case-control study concerning 151 subjects, 102 hypertensives and 49 normotensives. We created a rapid mini-sequencing method based on dye-terminator cycle sequencing to simultaneously detect the M235T and T174M variants of the AGT gene for each subject. RESULTS: The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (chi 2 = 11.106, P = 0.004 and chi 2 = 6.453, P = 0.011, respectively), whereas those of the T174M variant did not differ (chi 2 = 0.004, P = 0.998 and chi 2 = 0.032, P = 0.858, respectively). The odds ratio for hypertension was 3.64 (95% confidence interval 1.56-8.49) for subjects with the C/C genotype of the M235T variant compared with other genotypes of 2.87 (95% confidence interval 1.76-4.68) for those carrying allele C versus those carrying allele T. CONCLUSION: The molecular variant M235T, but not T174M, of the AGT gene is associated significantly with essential hypertension in this Taiwanese population. The genotype C/C or allele C is a risk factor for hypertension. The underlying mechanism of this association needs to be elucidated further.     

Chordoma in childhood and adolescence. A clinicopathologic analysis of 12 cases

Chordoma is a distinctly uncommon neoplasm in the first two decades of life. To characterize further its clinicopathologic features in this age group, we studied 12 chordomas from six males and six females (age range, 1 month to 20 years at diagnosis), with a mean age of 6 years. Six tumors arose in the clivus, four in the cervical or thoracic vertebrae, and two in the lumbar and sacrococcygeal areas. The clinical presentations reflected the location. Histologically, six cases were classic chordomas; the remaining six had atypical or nonclassic features of a round cell or spindle cell tumor. Immunohistochemical stains for vimentin and cytokeratin were positive in all cases tested, whereas epithelial membrane antigen was detected in 11 examples, and S100 protein reactivity was noted in nine lesions. The tumors were uniformly nonreactive for glial fibrillary acidic protein and carcinoembryonic antigen. Electron microscopy in six cases demonstrated large primitive cells with attenuated cell junctions, whorls of cytoplasmic filaments, vacuoles, and glycogen aggregates. Ten children had died of tumor at intervals of 3 weeks to 4.5 years after diagnosis and treatment. Lung, lymph nodes, and other organs were the distant metastatic sites in seven cases. These findings imply that chordomas in children are more variable histologically and may pursue a more aggressive clinical course than their adult counterpart. Immunohistochemical studies are particularly helpful in the differentiation of atypical chordomas from other round and spindle cell neoplasms.     

A model for the valuation of mass attendance and attendance duration of patients with malignant neoplasms (author''s transpl)

By means of a combination of two methods known in demography - life table and estimates for intercensal years - probabilities of prevalence of cancer patients and duration of disease from onset to death are calculated. Starting-points are the incidence know by cancerregistration and death certificates. The results of the model are compared with the results of a special point prevalence counting. Both methods gave about the same results.     

Neurological signs and frontal white matter lesions in vascular parkinsonism. A clinicopathologic study

BACKGROUND AND PURPOSE: The clinical characteristics and the pathological lesions of so-called vascular parkinsonism (VP) are still debatable. The purpose of this study was to define the core signs and symptoms and assess the cerebrovascular lesions in pathologically confirmed VP. METHODS: In the present study, VP was defined as the presence of parkinsonism and pathological evidence of cerebrovascular lesions but no depigmentation or Lewy bodies at the substantia nigra. We compared the clinical signs and symptoms of 24 VP patients with those of 30 age-matched patients with pathologically confirmed Parkinson's disease. We compared the brain pathology in VP patients with that in 22 age-matched patients with Binswanger's disease (BD) who had no parkinsonism according to clinical records. RESULTS: VP was characterized clinically by a short-stepped or frozen gait, lead-pipe rigidity, absence of resting tremor, and negative response to levodopa. Half or more of VP patients demonstrated pyramidal tract signs and pseudobulbar palsies. There was no significant difference in the extent of vascular lesions at the basal ganglia between patients with VP and with BD without parkinsonism. The extent of frontal white matter pallor tended to be less broad in VP than in BD without parkinsonism. In VP patients, the number of oligodendrocytes in the frontal white matter was significantly less than that in age-matched normal control subjects and significantly more than in those with BD. CONCLUSIONS: The core signs and symptoms of autopsy-proved VP differ from those of typical Parkinson's disease, and most VP patients had diffuse cerebral white matter lesions as well as basal ganglia lesions. VP might be related to frontal white matter lesions.     

AIDS pathology: infections and neoplasms in 55 fatal AIDS cases. A postmortem study

The study evaluated the incidence of infections and neoplasms in 55 out of 104 patients with AIDS who died in Poland from January 1986 to April 1994 (the estimated autopsy rate-52.8%). Histopathological examination revealed 103 infections and 11 neoplasms. In 40 persons (73%) either multiple infections or a neoplasm and an infection were diagnosed. Cytomegalovirus infection was most common. (65.5% of cases) followed by Pneumocystis carinii (24% of cases). These infections were the leading cause of death in 20% and 16% of cases, respectively. The results of this study showed a significantly lower incidence of Pneumocystis carinii, Kaposi's sarcoma and non-Hodgkin's lymphoma in comparison with the results of similar studies in countries with a large number of AIDS cases.     

Hamartoma of the breast, an underrecognized breast lesion. A clinicopathologic and radiographic study of 25 cases

This study investigated the clinical, radiographic, and pathologic features of breast hamartoma. The patients ranged in age from 18 to 89 years, with a mean age of 45 years, and a median age of 43 years. Seventy-five percent of the patients were asymptomatic, other than reporting a breast lump. In two patients, the lesions recurred at 7 and 18 months after the initial resection. The clinical diagnoses were fibroadenoma in 10 cases, carcinoma in 5 cases, hamartoma in 4 cases, and phyllodes tumor and lipoma in 2 other cases. Mammograms were available in 12 cases, the majority of which showed a well-defined mass of homogeneous density. Grossly, these lesions were oval to round, well-circumscribed masses, ranging in size from 1 to 7 cm in maximum dimension (mean, 3.9 cm). The microscopic appearance of these tumors corresponded to their gross appearance. Lesions that were grossly firm, rubbery, and white consisted largely of dense fibroconnective tissue with variable amounts of glandular elements with little adipose tissue. Softer, pale, yellow lesions contained more adipose tissue. A consistent and important diagnostic feature was the presence of both lobules and ducts, in contrast to fibroadenoma in which lobules are often absent or rare. The current trend of mammographic breast screening has made us aware that mammary hamartomas are not uncommon. These lesions may go unrecognized by the pathologists because they show all the constituents of normal breast tissue and may be reported as "no pathological diagnosis" or "normal breast tissue," which are inappropriate diagnoses for a lesion that presents as a palpable and a well-circumscribed mass.     

OraTest. A new method for differentiating between benign and malignant oral tumors

Recent cloning and expression studies have revealed that the opioid mu-, delta-, kappa- and orphan receptors are seven-transmembrane domain receptors whose actions are mediated through activation of guanine nucleotide binding protein (G-protein). The activation of G-proteins by the opioid receptor can be measured by assessing agonist stimulation of membrane binding of the non-hydrolyzable analog of guanosine triphosphate (GTP), guanosine-5'-O-(3-[35S] thio) triphosphate ([35S] GTP gamma S). Our recent data suggest that 1) the level of spinal mu-, delta-, kappa- and orphan-receptor agonist-stimulated [35S] GTP gamma S binding closely parallels that of receptor binding densities, 2) the neuroanatomical distribution of opioid agonist-stimulated [35S] GTP gamma S binding relates to receptor binding distribution, 3) newly isolated opioid peptides, endomorphin-1 and -2, can activate G-proteins by specific stimulation of mu-receptors and act as partial agonists with moderate catalytic efficacies, 4) mu-receptor densities could be rate-limiting steps in the G-protein activation by mu-agonists in the spinal cord region. In conclusion, opioid agonist-stimulated [35S] GTP gamma S binding can provide a functional method to localize receptors not only by their ability to bind ligands, but also according to their ability to activate an intracellular signal transducer.     

In-vitro high-resolution ultrasonography of benign and malignant lymph nodes. A sonographic-pathologic correlation

RATIONALE AND OBJECTIVES: The authors assess the value of combining high-resolution ultrasonography (HRUS) findings in a scoring scale for distinguishing malignant from reactive lymphadenopathy and explain the pathologic causes of altered nodal sonographic architecture. MATERIALS AND METHODS: Sixty-one nodes obtained from 32 consecutive patients were prospectively scanned with 7.5-MHz ultrasound probes in a waterbath. Three sonographic features--long-to-short axis ratio (L/S), hilar width, and cortical width--were graded on a 5-level scoring scale (0-4). Nodes scored > or = 3 were considered malignant and < or = 2 benign. Subsequently, all nodes were microsectioned in a plane matching the sonograms, allowing direct sonographic-pathologic correlation. RESULTS: Eighty-two percent of nodes were correctly characterized using the above cut-off point (sensitivity: 87%, specificity: 74%). Eighty-three percent of nodes scored 4 were malignant and 95% scored 0 were benign. Eighty-two percent of nodes with L/S < 2, 81% with no hilus, and 70% with eccentric cortical widening were malignant, whereas 72% with L/S > or = 2, 86% with a wide hilus, and 91% with a narrow cortex were benign. Sonographic-pathologic correlation showed that tumor infiltration results in rounded nodal shape, loss of hilar echogenicity and cortical widening, whereas reactive disease tends to preserve nodal architecture. CONCLUSION: Morphologic changes detectable using HRUS help distinguish benign from malignant lymph nodes.     

Psychopathological assessment and diagnosis. A study of specificity of single symptoms

The importance of single symptoms in the diagnostic process has not been adequately studied, mainly because of the complexity of the information involved. The aim of the present study is to investigate the interconnection between psychopathological assessment and diagnostic classification, with the aid of a nonparametric, inductive pattern recognition method. Using the concept of inductive logic and a theory of inductive knowledge acquisition, a model has been developed to describe psychopathological assessment and diagnostic classification. Based on a comprehensive psychopathological assessment in 837 patients with 14 different diagnoses, classification values were calculated for specific symptoms in different diagnostic groups. Furthermore, nonparametric statistical procedures have advantages over discriminant analytic approaches: more information is utilized in differentiating the groups and differentiations can be made between more groups, whereby the rate of correctly classified cases is comparable with discriminant analytic approaches. The pattern recognition method appears to illustrate the multidimensional, medical decision-making in a comprehensible way.     

Levodopa and malignant melanoma--case report and review of the literature. A contribution to causal relationship between levodopa and the development of malignant melanoma

We have found that azide-resistant mutants of Salmonella typhimurium and of other bacteria studied produce a substance which inactivates the azide. The production of this substance was proved by the demonstration of a satellite growth of azide-sensitive cells around colonies of azide-resistant mutants and by testing azide inactivating properties of culture filtrates of the azide-resistant strains. The same substance was found to be present in lower concentrations in culture filtrates of wild-type sensitive strains. In both cultures of sensitive strains, it was apparently produced by the resistant mutants and not by the sensitive cells. The substance does not pass across a dialysis membrane and is heat stable. It has a high molecular weight but is not a protein.     

Congenital retardation and central motor defect with later evolution of seizure disorder, orofacial dysplasia, and amyotrophy. A clinicopathologic report

Retarded mental and motor development was observed during the first year of life of a full-term female who had been delivered with difficulty. Generalized psychomotor seizures and dysplastic "acromegalic" facial changes began to develop when she was 8 years old, and generalized amyotrophy developed over the next several years. The course was generally progressive, and she died at age 31. A variety of clinical laboratory studies were nondiagnostic. Autopsy findings showed normal brain weight and normal-appearing cerebral hemispheres, a peculiar atrophy of the inferior portion of the cerebellar hemispheres, a demyelinating process in the dorsal columns of the cervical and thoracic spinal cord, and lateral column and motor neuron degeneration. The pathogenesis of the syndrome is undetermined.     

Acute renal failure--etiologic and therapeutic considerations. A five-year experience at a single institution

In the present study we highlight the epidemiology, etiologic spectrum, and evaluation of ARF in adults. We then expand on the pathophysiologic mechanisms of renal failure and discuss the rationale for current therapeutic strategies in ARF patients. A total of 79 patients (45 male, female 34), aged 18-75 years (median age 51.2 +/- 17.7 years) with acute renal failure were studied in 5 years (January 1990 through October 1995). Emergency hemodialysis sessions following an acute anuric episode were instituted in 39 cases (49.3% of all patients). The median number of hemodialysis procedures per patient treated at our institution was 3.2 +/- 1.9. The total number of acute interstitial nephritis-associated ARF was 40. In 30 of them (75%) the acute renal insult included a combination of several therapeutic antimicrobial agents, in 2 cases (5%) ARF followed the administration of nonsteroidal anti-inflammatory drugs, in 1 (2.5%) it resulted from a combined therapeutic regimen and in the remaining 5 (12.5%) from the application of a single drug. Acute interstitial nephritis developed in 2 patients following a viral infection. In the hemodialysis-treated ARF group 12 patients (29.77%) had interstitial nephritis and 2 patients (5.13%) presented with renal impairment for an unspecified period of time preceding the development of overt ARF. In a subset of this group of patients, ARF occurred in 7 patients (17.95%) following an urologic intervention, in 8 patients (20.51%) as a consequence of thermal or mechanical trauma or intoxication and in 3 cases (7.69%) it resulted from fever of unknown origin. Three patients with postoperative peritonitis and 4 other (10.26%) with postoperative complications were encountered in our series. No cases of septic abortion-related or obstetric-related ARF were recorded. 92.3% of all hemodialysis-treated patients seen at our Institution had received a combination of antibiotics and only 2 patients had been pre-treated with a single antimicrobial agent. Our results underscore the strong tendency towards diversity in the etiologic spectrum of clinical entities causing ARF and the increase in the number of acute interstitial nephritis. These factors highlight the importance of precise dosing and administration of drugs, especially antibiotics, as well as the duration of antibiotic treatment.