The ACTN3 R577X polymorphism is associated with inflammatory myopathies in a Mexican population.

BACKGROUND: The ACTN3 gene encodes the fast muscle protein α-actinin-3. The ACTN3 R577X polymorphism is a premature stop codon and results in absence of α-actinin-3 in 577XX homozygotes. The aim of this study was to determine the ACTN3 genotype in idiopathic inflammatory myopathies (IIMs). METHODS: We performed ACTN3 genotyping on 27 patients with dermatomyositis (DM), 10 with polymyositis (PM), and 85 healthy subjects. Muscle enzyme levels of creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were recorded at the time of diagnosis and recruitment. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the allele frequency was analysed. RESULTS: A total of 36% of healthy subjects had the ACTN3 577XX polymorphism (α-actinin-3 deficiency), 18% had the 577RR (homozygous wild type) genotype, and 46% 577RX (heterozygous). In DM/PM, 70% had the ACTN3 577XX polymorphism, 6% RR, and 24% RX [odds ratio (OR) 4.12, 95% confidence interval (CI) 1.67-10.33, p < 0.001]. In healthy subjects, the R allele was present in 41% and the X allele in 59% compared to 18% and 82%, respectively, in the IIM group (OR 3.21, 95% CI 1.57-6.66, p < 0.001). Thus, the ACTN3 577X allele seemed to increase the risk of developing IIM, and DM in particular, although this was not related to severity of expression of the phenotype. CONCLUSIONS: The ACTN3 577X allele appeared to increase the risk of developing IIM; 70% of IIM patients were deficient in α-actinin-3. By contrast, ACTN3 577XX patients seemed to have less severe disease as reflected in lower muscle enzyme levels.

Paecilomyces peritonitis: case report and review of the literature.

While filamentous fungi are a rare cause of peritonitis in peritoneal dialysis patients, there is increasing recognition of Paecilomyces species as pathogens in such patients. We herein report a case of fungal peritonitis secondary to the filamentous Paecilomyces variotii species. The patient had a long and ultimately fatal course of illness despite catheter removal, discontinuation of peritoneal dialysis, recurrent intraabdominal abscess drainage, and prolonged courses of antifungal therapy. Our experience with this case and a review of the literature suggests that infection with this fungus can cause substantial morbidity and is probably best treated with prompt catheter removal, aggressive antifungal therapy and vigilant observation for complications.

Immunohistochemical detection of betaine-homocysteine S-methyltransferase in human, pig, and rat liver and kidney.

Betaine-homocysteine S-methyltransferase (BHMT) has been shown to be expressed at high levels in the livers of all vertebrate species tested. It has also been shown to be abundant in primate and pig kidney but notably very low in rat kidney and essentially absent from the other major organs of monogastric animals. We recently showed by enzyme activity and Western analysis that pig kidney BHMT was only expressed in the cortex and was absent from the medulla. Using immunohistochemical detection, we report here that in human, pig, and rat kidney, BHMT is expressed in the proximal tubules of the cortex. Immunohistochemical staining for BHMT in human, pig, and rat liver indicate high expression in hepatocytes. The staining patterns are consistent with cytosolic expression in both organs.

Hepatoid carcinoma of the pancreas.

BACKGROUND: The majority of primary extrahepatic neoplasms exhibiting features of hepatocellular carcinoma in terms of morphology, immunohistochemistry, and behavior have been described in the stomach. To the authors' knowledge only a few cases have involved other organ sites. They frequently are associated with other histologic type tumors such as adenocarcinoma, and portend an aggressive behavior. METHODS: Two examples of hepatoid carcinoma arising from the pancreas are reported in the current study. RESULTS: One case was a malignant islet cell tumor with a full-blown clinical syndrome of glucagon overproduction, histologic evidence of hepatocytic differentiation, bile production, and alpha-fetoprotein (AFP) positivity. The second tumor was a ductal carcinoma showing periodic acid-Schiff positive and diastase-resistant hyaline globules, AFP production, and ultrastructural resemblance to hepatocytic cells. CONCLUSIONS: The rare observation of cellular phenotypic transformation that corresponds with the process of hepatocytic transdifferentiation of pancreatic cells demonstrated in animal models and the common embryologic foregut derivation of the pancreas and liver also may explain the phenomenon of pancreatic hepatoid carcinoma.

Fine needle aspiration biopsy of mastitis secondary to empyema necessitatis. A report of two cases.

BACKGROUND: Empyema necessitatis is a relatively rare entity. Two instances of mastitis secondary to empyema necessitatis, diagnosed by fine needle aspiration biopsy are reported. CASES: One case was tuberculous in etiology and was initially recognized by cytologic findings of epithelioid and granulomatous cellular reactions and the presence of acid-fast bacilli, which were subsequently cultured and speciated as Mycobacterium tuberculosis. The other case was due to coexisting Actinomyces and Actinobacillus. These organisms were cytologically suggested by "sulfur" granules of filamentous, gram-positive bacilli, admixed gram-negative coccobacilli and Splendore-Hoeppli phenomenon in an exudative cell background and were confirmed by microbiologic culture as Actinomyces israelii and Astinomyces actinomycetemcomitans, respectively. CONCLUSION: The usefulness of fine needle aspiration cytology in the diagnosis of empyema necessitatis, supported by ancillary microbial culture, histochemistry, and radiographic imaging, is well illustrated by these two cases.

Cytopathologic evaluation of lung carcinomas presenting as brain metastasis.

Brain metastasis is an uncommon initial presentation of lung carcinoma. One arm of this analysis is a retrospective review of 137 cases of surgically diagnosed solitary brain metastasis, which were eventually found to be of lung origin, encountered at Hines VA Hospital during the period 1958 to 1996. The second arm is composed of fine-needle aspiration biopsy specimens of primary lung tumor in 23 patients with an initial clinical diagnosis of brain metastasis and without the benefit of surgery, seen from 1981 through 1996. Our results in both analyses indicate that pulmonary adenocarcinoma is the predominant primary tumor that initially manifests as a brain metastasis, approaching 76% (107 and 17 cases, respectively), followed by small-cell carcinoma at 20% (24 and five cases, respectively) and large-cell undifferentiated carcinoma and squamous-cell carcinoma at 2% each. The predominance of adenocarcinoma as a source of brain metastasis in lung cancer patients probably reflects its rising incidence overall of late. Collateral findings also suggest that surgical resection of a solitary and small brain metastasis as well as of a discrete lung primary, whenever feasible, as the most effective procedure to improve survival and quality of life of patients.

Adenocarcinoma of the lung: electron microscopy of fine-needle aspiration biopsy specimens--a review of 73 cases.

During a 10-yr period, 128 consecutive cases of pulmonary adenocarcinoma of varying differentiation were diagnosed with percutaneous fine-needle aspiration biopsy. Sediments from the needle and syringe washings with 3% glutaraldehyde were obtained and processed for electron microscopic evaluation in 73 cases. Our results showed three types of adenocarcinoma: 62 cases of nonciliated bronchiolar cell origin, 6 cases of bronchioloalveolar cell origin, and 3 cases of mucous cell origin. In addition, there was an example of combined adenosquamous carcinoma and an instance of amphicrine carcinoma. Our study provided a more precise definition of the cytologic diagnosis and insight into the heterogeneity of lung adenocarcinoma. However, prognostic differences between cell types of lung adenocarcinoma were not observed.

Production of a rabbit anti-cockatiel immunoglobulin G and characterization of its cross-reactivities with immunoglobulin G of other psittacine species.

The purpose of this work was to produce rabbit anti-cockatiel immunoglobulin G (IgG) and compare its cross-reactivity with sera from eight other psittacine birds: Quaker parakeet, budgerigar, green-wing macaw, blue-fronted Amazon parrot, eclectus parrot, African grey parrot, Patagonian conure, Moluccan cockatoo. Cockatiel IgG did not bind to protein A or G; therefore, these proteins could not be used in column chromatography to isolate the IgG. A combination of serum IgG precipitation by ammonium sulfate and yolk IgG extraction from egg was loaded in sodium dodecyl sulfate-polyacrylamide gel upon which the IgG was resolved by electrophoresis. The resolved IgG in sodium dodecyl sulfate-polyacrylamide gel was stained with Coomassie blue, cut, crushed in phosphate-buffered saline, and injected into rabbits. The rabbit anti-cockatiel IgG produced in this way reacted with a single protein in gel immunodiffusion assay with all nine psittacine bird sera but not with those of chicken and ostrich. Immunoelectrophoresis confirmed the cross-reactivity of different psittacine sera with the anti-cockatiel IgG serum but not with ostrich and chicken sera. This antiserum detected antibody responses in sera from cockatiels vaccinated against chlamydial major outer membrane protein in an immunoblot assay.

Fine-needle aspiration cytology of epithelioid leiomyoblastoma.

Purpose. Epithelioid leiomyoblastomas comprise the majority of gastric sarcomas and are uncommon in other parts of the gastrointestinal tract. Diagnosis of this lesion by fine-needle aspiration cytology has been occasionally described in the literature. Two additional cases are herein reported.Subjects . A 66-year old male with an omental mass and a 47-year old male with a perihepatic tumor.Results and Discussion. Cytologic materials in both cases showed predominantly round or epithelioid cells, along with polygonal to spindle cells, occuring singly and in clusters, with oval to spindle-shaped nuclei.The nuclei were monotonous, usually banal, and centrally-located with only focal suggestion of pleomorphism and rare mitosis. Eosinophilic cytoplasm was noted in most of the cells, some demonstrating vacuolation. Electron microscopy supported a primitive smooth cell derivation of the neoplastic cells.Conclusions. The cytomorphology of the tumors of the two cases reported here is not adequately known. More cases need to be collected and studied.

Primary chondroblastic osteosarcoma of the lung.

Purpose. Primary extra-osseous osteosarcomas are uncommon lesions, and those originating within the lung are especially rare, with few case reports existing in the literature.Patient. We report the case of a 48-year-old male smoker with a primary osteosarcoma of the right lower lung lobe.Results. Diagnosis was based on histopathological findings of a poorly differentiated sarcoma with malignant cellular components of osteoid and chondroid matrix, along with immunohistochemical and electron microscopy confirmation. Extensive clinical and radiographic evaluation failed to reveal any tumor at other anatomical sites.

Utilization of fine-needle aspiration cytology in the diagnosis of neoplastic superior vena caval syndrome.

Superior vena caval syndrome often presents as an acute or subacute oncologic emergency that requires immediate action, usually with high-dose radiotherapy. With improved chemotherapeutic regimens for various malignancies, prompt and appropriate treatment of the syndrome is possible. Tissue diagnosis, therefore, is pursued, but invasive procedures are commonly associated with technical difficulties and complications. We find fine-needle aspiration biopsy a rapid, highly reliable, and well-tolerated procedure in selected situations and herein report 17 patients with initial presentation of superior vena caval syndrome efficaciously diagnosed with fine-needle aspiration cytology. The cell types were eight lung small-cell carcinomas, four poorly differentiated adenocarcinomas, two undifferentiated large-cell carcinomas, and one each of malignant large-cell lymphoma, myxoid liposarcoma, and thymic large-cell neuroendocrine carcinoma. Further experience, however, is warranted with this widely available procedure.

Multivesiculated macrophages: their implication in fine-needle aspiration cytology of lung mass lesions.

Alveolar macrophages are almost invariably present in percutaneous fine-needle aspiration cytology of the lung. They may predominate, appear foamy and finely vesiculated, or may reflect the cellular composition of the lung mass lesion. In a review of 172 cases of "negative for malignant cells" from the percutaneous lung fine-needle aspiration cytology file in an 8-year period at Hines VA Hospital, the vacuolated macrophages were evaluated qualitatively and quantitatively. Among the 53 cases (34%) showing vacuolated macrophages, only 5-25% of the cells were multivesiculated, the cytoplasmic vacuoles were few, focal, and occasionally global, and the majority of the vacuolated macrophages contained anthracotic or hemosiderin pigments. One case exhibited striking multivesiculation in at least 95% of macrophages and also in bronchial and alveolar cells, fibroblasts, and endothelial and inflammatory cells, a finding consistent with amiodarone toxicity (index case 1). The diagnosis was confirmed on subsequent transbronchial lung biopsy. In another patient with clinical HIV infection, the multivesiculation was also seen in 95% of the macrophages with associated acute inflammatory exudate, coccobacilli, and a positive culture for Rhodococcus equi (index case 2). In most cases, the vacuolated macrophages are reactive and inflammatory. Occasionally, as in our index cases they may actually indicate a specific diagnosis.

Metastasis of unknown origin: the role of fine-needle aspiration cytology.

Metastasis of unknown origin (MUO) manifests either as a tumor deposit in an organ, often cervical lymphadenopathy, or as a multiorgan carcinomatosis. As a diagnostic and therapeutic challenge, the definition of its cell type and possibly its origin is imperative, although a limited diagnostic investigation is usually recommended. At Hines VA Hospital from 1986 to 1994, there were 116 cases with admitting clinical diagnosis of MUO, evaluated by fine-needle aspiration cytology (FNAC). The ages of patients ranged from 29 to 82 years (mean 56 years). All were male; Caucasians predominated. The FNAC examination with Diff-Quik and Papanicolaou smears were complemented with special and immunostains in 48 cases (41%) and electron microscopy in 93 cases (80%). The FNAC involved lymph nodes in 57 cases (49%), liver in 27 cases (23%), skin in 22 cases (19%), bone in six cases (5%), lung in three cases (3%), and pleura in one case (1%). The neoplasm was generally cell typed, and there were 60 adenocarcinomas/poorly differentiated carcinomas, 26 small-cell carcinomas (SCC), 23 squamous-cell carcinomas (SQCC), and six undifferentiated large-cell carcinomas. The primary source was defined in 30 cases (26%), consisting of lung in 11 cases, prostate in nine, kidney in four, colon in four, pleura in one, and peritoneum in one. Clinical correlation also supported a lung origin for the SCC, while the majority of the SQCC in upper and middle cervical lymph nodes were considered head-and-neck tumors. Our results affirm that FNAC is a viable and simple procedure in MUO investigations.

Fine-needle aspiration cytology of extraskeletal Ewing's sarcoma.

Extraskeletal Ewing's sarcoma (EES) is a round-cell malignancy that manifests most commonly in the paravertebral and intercostal regions. It occurs predominantly in adolescents and young adults, between the ages of 10 and 30 yr, and follows an aggressive course with a high recurrence rate. Distant metastasis is also common. The tumor is often confused with other round, small-cell neoplasms, including primitive neuroectodermal tumor, neuroblastoma, embryonal rhabdomyosarcoma, and lymphoma. This report pertains to a fine-needle aspiration cytologic diagnosis of EES, supported by clinicopathologic and fine structural correlations in a 56-yr-old man who presented with a rapidly growing, massive, right groin mass. The smears showed a diffuse cellular population of malignant round cells composed of two types: one group of larger cell exhibiting a thin-rim, pale cytoplasm, less hyperchromatic nuclei, nucleoli, and diffusely dispersed chromatinic nuclear details; and the second group of smaller and darker cells with highly hyperchromatic and almost smudged nuclei. These are chief cells and dark cells, respectively. Special studies revealed significant intracytoplasmic glycogen and positive vimentin and HBA-71 immunostaining. Cytogenetic findings of chromosomal 11;22 translocation is also supportive of the diagnosis of EES.

Breast and cutaneous mycobacteriosis: diagnosis by fine-needle aspiration biopsy.

The breast and skin are considered to be rare sites of extrapulmonary mycobacterial infection, comprising 0.1% to 0.5% of all tuberculosis cases, respectively. Fine-needle aspiration biopsy (FNAB) is a rapid and minimally invasive approach to diagnose extrapulmonary tuberculosis, and has been used successfully in identifying tuberculous lesions in the lymph nodes, thyroid, kidney, pancreas, vertebrae, and testis. Two cases of extrapulmonary mycobacteriosis diagnosed by FNAB are described: a 59-year-old Hispanic male with cutaneous mycobacterial infection of the head and neck region, and a 58-year-old white male with a unilateral tuberculous mastitis. In both instances, the FNAB material demonstrated acute neutrophilic exudate, few isolated aggregates of epithelioid histiocytes and lymphocytes, and on Fite-Farraco stain mycobacteria. Reported cases of tuberculosis diagnosed by FNAB have been few; this is the first case of cutaneous tuberculosis diagnosed by FNAB.

Pleural effusion cytology of embryonal rhabdomyosarcoma.

This case report concerns an embryonal rhabdomyosarcoma of the testis in a 31-yr-old white male patient who underwent radical left orchiectomy, followed by combined irradiation and chemotherapy, and who 2 yr later presented with dyspnea at rest, nonproductive cough, and lower back pain for 1 wk. Chest radiographs demonstrated a bilateral pleural effusion and diffuse infiltrating lesion of the pleurae, mimicking a mesothelioma. The pleural fluid displayed noncohesive, malignant, small, round cells about 2-5 times larger than mature lymphocytes. They had large, darkly stained, pleomorphic nuclei and bubbly cytoplasm with poorly defined borders. The diagnosis of embryonal rhabdomyosarcoma was supported by a positive myosin immunostaining and ultrastructural findings of intracytoplasmic actin and myosin-type microfilaments. Our case is also notable in that the tumor was a pure rhabdomyosarcoma involving a testicular origin, and the patient is the oldest reported in the literature.

Anaplastic carcinoma of the colon: clinicopathologic study of eight cases of a poorly recognized lesion.

Eight cases of a distinctive histological variant of bowel cancer characterized by an anaplastic morphology were identified from 2,650 colonic malignancies (0.3%). The tumors were histologically composed of sheets of anaplastic tumor cells with frequent atypical mitoses, absence of gland formation, and mucicarmine and periodic acid-Schiff (PAS) negativity. Positive immunostaining for cytokeratin and vimentin was observed in eight cases and for epithelial membrane antigen in three; whereas carcinoembryonic antigen, alpha-fetoprotein, S-100 protein, HMB-45 antimelanoma antigen, leukocyte common antigen, and neuroendocrine markers were uniformly negative. Ultrastructural examination demonstrated intercellular tight junctions, focal surface microvilli, and apical terminal webs or long rootlets of microfilaments supporting a colonic derivation. At the time of diagnosis, metastases to regional lymph nodes were found in seven cases and to the liver in six. All patients in this study died of tumor within 9 months. This report emphasizes a poorly recognized variant of colonic carcinoma, characterized by a high degree of anaplasia and malignant behavior. The differential diagnosis for these lesions is discussed.