A uterine leiomyosarcoma that became positive for HMB45 in the metastasis

Uterine smooth muscle tumors are usually spindle cell lesions, but a minority is composed of epithelioid cells. Foci of clear cells can be found in these latter tumors. Recently, it has been shown that some of these tumors can be positive for HMB45, and some authors have advocated calling these lesions perivascular epithelioid cell (PEC) tumors or PEComas. The case we describe here clearly shows that the so called PEC is just a smooth muscle cell capable of changing its immunophenotype. The patient involved is a 29-year-old black woman who was found to have an epithelioid leiomyosarcoma of the uterus in November 1995. She was treated with a simple hysterectomy and bilateral salpingo-oophorectomy. A metastatic lesion was found in her liver. She, therefore, also received chemotherapy and was free of disease until October 2002, when a recurrent tumor was detected in her spine. After undergoing resection of the lesion at 2 different times, in 2002 and 2003, the patient was treated with radiotherapy and is currently receiving chemotherapy. On microscopic examination, the tumor in the uterus and liver both proved to be an epithelioid leiomyosarcomas that was diffusely positive for smooth muscle actin. Approximately 15% of the cells had clear cytoplasm, but sections from 2 different blocks were completely negative for HMB45. However, although the tumors resected from the spine in 2002 and 2003 showed features similar to those of the uterine neoplasm, but with a lower percentage of cells positive for smooth muscle actin and more clear cells, several of the clear cells were positive for HMB45. To the best of our knowledge, this is the first case of a uterine smooth muscle cell tumor that became positive for HMB45 when it metastasized.     

Soft-tissue angiomatosis in adulthood: a case in the forearm showing a prominent myxoid adipose tissue component mimicking liposarcoma

Soft-tissue angiomatosis is a rare condition characterized by diffuse proliferation of benign vascular structures, accompanied by mature adipose tissue, which affect a large segment of the body in a contiguous fashion. Most patients present in childhood or adolescence. We report a case of large soft-tissue angiomatosis, located in the left forearm of a 65-year-old man, which showed extensive intramuscular and intermuscular infiltration, and embracement of the radius and the main vascular and neural bundles of the forearm. Due to the deep location, large size, ill-defined limits and non-homogeneous composition with areas suggestive of an adipose component in the radiological examination, the lesion raised the possibility clinically of a liposarcoma. The myxoid adipose tissue component of the lesion, a feature previously undescribed, and the predominance of small, capillary-sized vessels were considered concordant with the clinical diagnosis. This presentation is rare. The features of the lesion made complete surgical excision impossible and amputation of the extremity was considered the best treatment. The main differential diagnoses include infiltrating lipoma, myxolipoma, angiomyxolipoma, angiolipoma, intramuscular angioma, liposarcoma and low-grade myxofibrosarcoma. In conclusion, angiomatosis might simulate liposarcoma, particularly if the mass is large, heterogeneous, myxoid and appears later in life.     

An ELISA serum assay for autoantibodies to HSP70 in immune-mediated hearing loss

A Western blot to detect anti-HSP70 autoantibodies has been reported to be of diagnostic value for immune-mediated hearing loss patients. While setting up this Western blot in our lab, we detected two main problems. First, some patients were positive for antibodies to a 70-kDa protein when tested against a whole cell lysate, but negative if the antigen used was purified HSP70. Second, if high amounts of purified HSP70 were loaded on the gel, both patients and healthy controls were positive. We have developed and optimized an ELISA as an alternative to the Western blot. This assay is more appropriate to identify positive and negative individuals because it is semi-quantitative. The ELISA is also more sensitive, requiring very low concentrations of the antigen and thus minimizing false positives. Finally, we demonstrated that immune-mediated hearing loss patients recognize mainly the native form of HSP70, a fact that potentially leads to false negatives when a denaturing Western blot assay is used for diagnosis. To test the diagnostic value of the ELISA, we performed a blind test with 70 hearing loss patients, as well as 30 healthy controls. A sensitivity of 84% and a specificity of 93% were obtained, superior to what has been reported so far for the Western blot.     

Breast carcinoma with choriocarcinomatous features

Although breast carcinomas have been shown to produce various ectopic substances, including human chorionic gonadotropin, it is rare to identify morphologic differentiation compatible with the hormone produced by a tumor. Presently, only eight cases of breast carcinoma with focal choriocarcinomatous differentiation have been reported in the literature. This article describes the pathologic findings, immunohistochemical profile, and clinical course in two additional cases of this unusual variant of breast carcinoma. In the first case, the tumor had morphologic features suggestive of medullary carcinoma, and the patient is doing well 12 months after presentation. In the second case, the tumor was locally advanced at presentation with histologic features consistent with metaplastic carcinoma having squamous, sarcomatoid, and choriocarcinomatous elements. The patient presented with extensive multifocal metastases 6 months after the initial presentation and is not responding well to standard or experimental treatment regimen. Immunostaining for the beta subunit of human chorionic gonadotropin was localized mostly, but not entirely, to multinucleated syncytiotrophoblast-like giant cells within both tumors.     

Evidence-based medicine, medical decision analysis, and pathology

Recent advances in molecular pathology and other technologies such as proteomics present pathologists with the challenge of integrating the new information generated with high-throughput methods with current diagnostic models based mostly on histopathology and clinicopathologic correlations. Parallel developments in the field of medical informatics and bioinformatics provide the technical and mathematical methods to approach these problems in a rational manner. However, it remains unclear whether pathologists or other medical specialists will become primarily responsible for the development and maintenance of these multivariate and multidisciplinary diagnostic and prognostic models that are hoped to provide more accurate, individualized patient-based information. Evidence-based medicine (EBM) and medical decision analysis (MDA) are relatively new disciplines that use quantitative methods to assess the value of information, differentiate fact from myth, and integrate so-called best evidence into multivariate models for the assessment of prognosis, response to therapy, selection of laboratory tests, and other complex problems that influence individual patient care. We review from an epistemological viewpoint the current approach to information in pathology and describe some of the concepts developed by the practitioners of EBM and MDA.     

Chromophobe renal cell carcinoma with sarcomatoid transformation

We present a rare case of a chromophobe renal cell carcinoma that progressed to a high-grade spindle cell sarcoma. The tumor affected a 50-year-old man who had presented with right upper quadrant discomfort and hematuria and subsequently underwent a right radical nephrectomy. Microscopically, the tumor was composed of two distinct components, a chromophobe renal cell carcinoma and a sarcomatoid component. The sarcomatoid component had exhibited aggressive behavior by spreading to a regional lymph node. This case report shows that chromophobe carcinoma can develop a sarcomatoid transformation with a high propensity for invasive growth and metastasis.     

Cloning,isolation, and IgE-binding properties of Helix aspersa (brown garden snail) tropomyosin

BACKGROUND: Gastropod consumption is quite frequent in the Mediterranean countries and cross-reactivities with crustaceans have been described, but the mechanism of this allergenic cross-reactivity has not been studied in detail. This study aimed to produce recombinant Helix aspersa (brown garden snail) tropomyosin and investigate its implication for cross-reactivity among invertebrates. METHODS: A tropomyosin-specific cDNA encoding H. aspersa tropomyosin was synthetized, and recombinant allergen was overexpressed in Escherichia coli as nonfusion protein. IgE-binding reactivity was studied by immunoblotting and immunoblot inhibition experiments with sera from snail-allergic patients. RESULTS: Cloned brown garden snail tropomyosin shares high homology with other edible mollusk tropomyosins (84-69% identity) as well as with those from arthropods (65-62%), and less homology with vertebrate ones (56% identity). Tropomyosin reacted with 18% of the sera from patients with snail allergy. Inhibition experiments, using natural and recombinant tropomyosins, showed different degrees of cross-reactivity between invertebrate tropomyosins. Sera from snail-allergic subjects recognized tropomyosins in both mollusks and crustacean extracts. CONCLUSIONS: Tropomyosin represents a minor allergen in snail extracts, but it is clearly involved in invertebrate cross-reactivity.     

The pathogenesis of inflammatory muscle diseases: on the cutting edge among the environment,the genetic background,the immune response and the dysregulation of apoptosis

Inflammatory muscle diseases (IMD), including dermatomyositis (DM) and polymyositis (PM), affect skeletal muscle, leading to profound tissue modification. The etiology of IMD is unknown, but multiple steps of the disease pathogenesis have been identified. The main alterations involve the immune response. Cellular infiltrates found in the muscle provide strong evidence for the involvement of a preferential immune mechanism of muscle damage. The pathologic differences found between PM and DM indicate a different role played by cell-mediated and humoral immune alterations. It is well accepted that in the pathogenetic pathway both host genes and environmental factors are involved. Apoptosis, or programmed cell death, is a complex process that plays a key role in many physiological events. It regulates the turnover of immune cells and is one of the mechanisms involved in ensuring a competent, non-autoreactive repertoire of lymphocytes. Apoptosis as a mechanism of muscle fibre death has been described in several neuromuscular disorders and muscular dystrophies, and evidence of a lack of apoptosis in IMD suggests a failure of apoptotic clearance of inflammatory cells playing a role in the maintenance of chronic cytotoxic muscle fibre damage. Most likely, the failure of apoptosis seems to be the main hallmark of the pathogenesis of IMD.     

Virilizing mature ovarian cystic teratomas

 Three further cases of mature benign cystic teratomas of the ovary associated with virilization are added to the three previously reported in the literature. They were found in postmenopausal, obese, diabetic women aged 52, 61, and 67 years. The patients presented with hirsutism and voice changes and clitoromegaly was present in one. Testosterone and androstenedione levels were elevated but promptly regressed after removal of the tumours. Histologically, sheets of stromal luteinized cells were found peripherally at the interface between the neoplasm and ovarian tissue. Luteinization of ovarian stroma induced by an unknown factor related to diabetes mellitus is the origin of the virilization. Received: 8 January 1997 / Accepted: 28 February 1997     

TT virus infection in human immunodeficiency virus type 1 infected mothers and their infants

Serum TT virus (TTV) DNA was determined in 83 human immunodeficiency virus type 1 (HIV 1) infected mothers [46 intravenous drug user and 37 non-intravenous drug user women] and their infants. Twenty-nine (34.9%) mothers were TTV infected. Infection was more frequent among intravenous drug user than non-intravenous drug user mothers [21/46 (45.6%) vs. 8/37 (21.6%); relative risk (RR): 2.1; 95% confidence limits (95% CL): 1.1-4.2; P = 0.023] and among intravenous drug users who carried on injecting than in those who had given it up [10/14 (71.4%) vs. 11/32 (34.3%); RR: 2.1 (95%CL: 1.2-3.7); P = 0. 021]. Infection was not related to age, CD4-positive T-lymphocyte counts, HIV 1 load, hepatitis B (HBV), G/GB-C (GBV-C/HGV), C (HCV) virus exposure. Eight (27.5%) infants born to TTV infected (but none of those born to TTV uninfected) mothers were TTV infected at a median age of 1.5 (range: 0.6-2.8) months. Infants born by vaginal/emergency caesarean delivery were more frequently infected than those born by elective caesarean delivery [7/16 (43.7%) vs. 1/13 (7.6%); RR: 2.1; 95%CL: 1.2-3.5; P = 0.033]. Infection in infants was not related to maternal CD4-positive T-lymphocyte counts, HIV 1 load, and HIV 1, HBV, GBV-C/HGV, or HCV transmission. No infant became TTV infected thereafter. No TTV infected child [follow-up: 31 (median; range: 6-60) months] showed signs of liver disease; five infants cleared TTV DNA after 22 (median; range: 6-60) months. TTV infection in HIV 1 infected women is prevalently related to intravenous drug user. The findings suggest that infants may acquire TTV at birth. Infection may persist without evident liver disease.