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Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE).

Overexpression of p185erbB2/neu has been detected in many adenocarcinomas, including prostatic cancer. In this study, a nontumorigenic cell line isolated from the rat prostatic epithelium (NbE) transfected with the activated oncogene p185neu-T was used to investigate the role of this oncogene in tumor progression. When clones overexpressing p185neu-T were injected orthotopically (1.5 to 2 x 10(6) cells) into the dorsal-lateral prostates of nude mice, prostatic tumors were detected in all mice injected and metastasis to the skeletal muscle in the rib area in 60-80% of the mice injected. Tumor and metastasis origin was confirmed by reselection with G418 and reverse transcriptase-polymerase chain reaction. Control cell lines produced no prostatic tumors or metastases. Incubation at low density (12500 cells/2 cm2) in serum-free medium revealed that clones overexpressing p185neu-T had a higher rate of [3H]thymidine incorporation than did control clones on 3, 5, and 7 d after plating (P < or = 0.0001) and constitutively overexpressed the 2.6-kb ornithine decarboxylase transcript. Additionally, clones overexpressing p185neu-T demonstrated an increased expression of epidermal growth factor receptor and p180erbB4, as judged by RNA blot analysis. Together these data support the hypothesis that overexpression of p185neu-T fosters tumor progression by several pathways, including induction of the metastatic cascade, increased proliferative capabilities, and increased expression of other members of the erbB2 gene family.

Adenocarcinoma↗

[Muscle metastasis as initial manifestation of adenocarcinoma of the stomach].

BACKGROUND: The presentation of gastric carcinoma with a metastasis in skeletal muscle is a distinct rarity. CASE REPORT: In a 72-year-old male patient a soft tissue mass behind the knee was biopsied rather late. Histology showed a metastasis of adenocarcinoma. The patient mentioned a slight feeling of strangulation, which led to endoscopy and the diagnosis of gastric carcinoma. Palliative chemotherapy was initially successful but the patient died after 21 months. DISCUSSION: Based on this case history, three points are discussed: how to biopsy a peripheral soft tissue mass, how to proceed when a metastasis of an unknown primary tumor is diagnosed, and the epidemiology of metastases to skeletal muscle.

Adenocarcinoma↗

Adrenal gland leiomyoma in a child with acquired immunodeficiency syndrome.

An adrenal gland leiomyoma was incidentally found at autopsy in a 2-year-old boy with acquired immunodeficiency syndrome (AIDS). Smooth muscle neoplasms have been described in pediatric AIDS and affect mainly the tracheobronchopulmonary, gastrointestinal, and hepatobiliary systems. An association between Epstein-Barr virus (EBV) and smooth muscle tumors in patients with AIDS has been described. This case is the first leiomyoma to be reported in the adrenal gland of a child with AIDS. EBV genome was demonstrated in the tumor by polymerase chain reaction.

Acquired Immunodeficiency Syndrome↗

Leiomyoma of the oral cavity: a light microscopic and immunohistochemical study with review of the literature from 1884 to 1992.

Leiomyoma is the most common benign neoplasm in the uterus and stomach but is rare in the oral cavity. There were only 5 oral cases in a series of 7748 leiomyomas of all sites. Benign smooth muscle neoplasms are classified into leiomyoma (solid leiomyoma), angiomyoma (vascular leiomyoma) and epithelioid leiomyoma (leiomyoblastoma). 6 cases diagnosed as leiomyoma were retrieved from the files of two oral biopsy services over the past 25 years. A light microscopic study including trichrome and phosphotungstic acid haematoxylin (PTAH) stains, and an immunohistochemical study with the following markers: desmin, muscle specific actin, myoglobin, vimentin, S-100 protein, neuron-specific enolase, factor VIII and Ulex europeus were done with suitable controls. The haematoxylin and eosin and Masson's trichrome stains supported a diagnosis of leiomyoma in all 6 cases but PTAH was positive in only 3 of them. The immunohistochemical study confirmed the diagnosis of leiomyoma in 3 cases. The other 3 were identified as granular cell tumour, myofibroma and neurofibroma, respectively. The review of the literature contributed the following data: mean age was 41 and median age 39 in 134/142 patients. A male sex prevalence 72/137 patients (54.0%) was noted. The lips were the most common site with 39 cases (27.46%) followed by the tongue 26 (18.30%), cheeks and palate 22 (15.49%), gingiva 12 (8.45%), and mandible 8 (5.63%). Prognosis of oral leiomyomas is excellent. Immunohistochemistry is a precise and reliable method for definitive diagnosis of oral leiomyoma.

Adolescent↗

Neck metastasis of a myxoid liposarcoma of the lower extremity.

We report the clinical features of two cases presenting metastatic neck tumors (in the anterior neck and submandibular regions) secondary to myxoid liposarcoma of the lower extremity. Both cases underwent repeated resection of primary legions of the lower extremities because of recurrences. Such repeated surgical procedures are thought to be a risk factor for distant metastasis resulting from hematogeneous dissemination of tumor cells, although there is considerable debate about multicentricity versus metastasis in liposarcomas. Where possible, therapy for liposarcomas should initially comprise complete and wide resection of the lesions. Combined therapy consisting of surgery and postoperative radiation and chemotherapy should be investigated in the future.

Adult↗

Intramuscular myxoma: a clinicopathologic study of 51 cases with emphasis on hypercellular and hypervascular variants.

Intramuscular myxoma (IM) is a benign soft-tissue tumor that presents as a deeply seated mass confined to skeletal muscle. Surgical excision is virtually always curative. Recurrence, even after incomplete resection, is exceptional. Intramuscular myxoma is classically described as hypocellular and hypovascular, and is composed of cytologically bland stellate and bipolar fibroblasts separated by abundant extracellular myxoid matrix. What is underemphasized, however, is that IMs often show areas of increased cellularity and vascularity that can lead to a mistaken diagnosis of sarcoma, especially myxofibrosarcoma, low-grade fibromyxoid sarcoma, and myxoid liposarcoma. In this report, we describe the clinicopathologic features of 51 IMs with special emphasis on those that exhibit these "hypercellular regions." The patients included 35 women and 16 men who ranged in age from 27 to 89 (mean 52) years. The tumors measured from 2 to 15 (average 5.6) cm and all had a gelatinous, lobulated cut surface. Histologically, they all demonstrated classic hypocellular, hypovascular regions. Thirty-eight tumors contained areas of relative increased cellularity that occupied from 10 to 80% of the tumor. These foci had increased numbers of cells, more prominent vascularity, and often increased collagen content. The hypercellular regions were not associated with cytologic atypia of the constituent cells, mitotic activity, or necrosis. Follow-up information was available for 32 patients and ranged from 3 to 108 (average 30) months. No tumor recurred or metastasized. Areas of hypercellularity are common in IMs. Their recognition is important to avoid an erroneous diagnosis of sarcoma.

Actins↗

A distinctive myointimal proliferation ('myointimoma') involving the corpus spongiosum of the glans penis: a clinicopathologic and immunohistochemical analysis of 10 cases.

This study details the clinicopathologic and immunohistochemical features associated with 10 cases of a distinctive myointimal proliferation involving the corpus spongiosum of the glans penis. Patients ranged in age from 2 to 61 years old (mean age, 29 yrs) and presented with a mass that varied in size from 0.5 to 1.9 cm in greatest dimension. The process was said to be present from 4 days to more than 6 months before surgical intervention. In each case, microscopic examination revealed almost identical histology. There was a prominent, often occlusive, fibrointimal proliferation with plexiform architecture involving the vasculature of the corpus spongiosum. The proliferation consisted of stellate-shaped and spindled cells embedded in abundant fibromyxoid matrix. Occasional lesional cells had well-developed myoid characteristics with moderately abundant eosinophilic cytoplasm, blunt-ended nuclei, and juxtanuclear vacuoles. Foci with degenerative changes, including "ghost cell" morphology, were also present. The myointimal process was extensively immunoreactive for alpha-smooth muscle actin, muscle-specific actin (HHF-35), and calponin, but it was minimally reactive for the D33 and D-ER-11 desmin clones. In contrast, native vascular smooth muscle encompassing the proliferation was strongly immunoreactive for all five markers. The myointimal cells were nonreactive for CD34, S-100 protein, and keratin. Factor VIIIrAg, CD31, and CD34 highlighted intact endothelial cells lining suboccluded vessels, scattered capillaries that penetrated the proliferation, and the normal uninvolved vasculature. The examined specimens were punch, incisional, or excisional biopsies, and in each instance, the process microscopically extended to the tissue margin. Follow-up data are available for 8 cases (median follow-up interval, 5 yrs 8 mos): one incompletely excised lesion with 6 months follow-up is stable but persistent, one lesion with 10 years follow-up regressed spontaneously after a punch biopsy, and the remaining six lesions have not recurred. A differential diagnosis of myofibroma, late-stage intravascular (nodular) fasciitis, vascular leiomyoma, and plexiform fibrohistiocytic tumor is discussed.

Adult↗

Hypertrophied palmaris longus muscle, a pseudomass of the forearm: MR appearance--case report and review of the literature.

Magnetic resonance (MR) imaging of the forearm was performed to evaluate a presumed forearm soft-tissue tumor in a 26-year-old man. Sagittal and axial images revealed a mass isointense to muscle just medial to the flexor carpi radialis tendon (in the expected location of the palmaris longus muscle). A diagnosis of hypertrophied palmaris longus muscle was made. The radiologist must be familiar with the MR imaging appearance of normal variants of the palmaris longus muscle, as this can obviate surgery.

Adult↗

Is anti-h-caldesmon useful for distinguishing smooth muscle and myofibroblastic tumors? An immunohistochemical study.

Misinterpretation of positive staining of antibodies to desmin, smooth muscle actin, and muscle actin as representing smooth muscle differentiation in the context of a spindle cell tumor is not uncommon. Anti-h-caldesmon is a promising novel immunohistochemical reagent for more specific smooth muscle differentiation. We studied 72 tumors (11 leiomyosarcomas, 26 malignant fibrous histiocytomas [MFHs], 11 fibromatoses, 11 cellular cutaneous fibrous histiocytomas [CCFHs], 5 malignant peripheral nerve sheath tumors, 4 synovial sarcomas, and 4 cases of nodular fasciitis), the reactive myofibroblastic response in 5 cases of acute cholecystitis, and the desmoplastic response surrounding 5 invasive breast carcinomas. Tissues were examined for expression of h-caldesmon, desmin, smooth muscle actin, and muscle actin. Diffuse staining for h-caldesmon was present only within the leiomyosarcomas. Focal staining for h-caldesmon involving less than 1% of lesional cells was present in 3 of 26 MFHs and 1 of 11 CCFHs. There was overlap in staining for the other "myoid" markers in all of the lesions that contained myofibroblasts. Anti-h-caldesmon seems to be a reliable marker of smooth muscle differentiation, and its inclusion in a panel of myoid immunohistochemical reagents should allow distinction of smooth muscle and myofibroblastic tumors.

Actins↗

Localized retroperitoneal lymphangioleiomyomatosis mimicking malignancy. A case report and review of the literature.

Lymphangioleiomyomatosis (lymphangiomyomatosis [LAM]), a rare disease of unknown etiology that is seen only in women usually in the reproductive period, generally presents with features of pulmonary involvement. Extrapulmonary involvement, such as angiomyolipomas and retroperitoneal adenopathy, can occur in up to 75% of cases. It is very rare, however, for patients to present with features of extrapulmonary LAM. We present an unusual, localized case of LAM presenting with neurologic symptoms related to a retroperitoneal mass in a 51-year-old woman. Magnetic resonance imaging showed that the mass involved retroperitoneal lymph nodes, and a clinical diagnosis of atypical sarcoma (possibly from a uterine primary) was made. The mass was resected, and a total abdominal hysterectomy was performed. On pathologic examination, the mass showed classic histologic features of LAM with spread along lymphatic channels in the lymph nodes. Intralymphatic projections simulated lymphatic metastasis; however, the cytologic features were benign. Immunostains revealed the tumor to be positive for smooth muscle actin and desmin, but negative for HMB-45. The uterus was unremarkable, except for a subserosal leiomyoma. Although intratumoral variability for HMB-45 has recently been described, to the best of our knowledge, this is the first documented case of HMB-45-negative, histologically classic LAM. Because of the presence of several atypical features in this case, such as age, location, compressive neurologic presentation, radiologic impression of atypical sarcoma, and HMB-45 negativity, we feel that this case may represent a distinct, as yet uncharacterized variant of LAM.

Diagnosis, Differential↗

p16 expression in the female genital tract and its value in diagnosis.

p16 is a cyclin-dependent kinase-4 inhibitor that is expressed in a limited range of normal tissues and tumors. In recent years, immunohistochemistry with p16 antibodies has been used as a diagnostic aid in various scenarios in gynecologic pathology. Diffuse (as opposed to focal) positivity with p16 in the cervix can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV). In cervical squamous lesions, p16 is positive in most high-grade cervical intraepithelial neoplasia (CIN) and in some cases of low-grade CIN, usually those associated with high-risk HPV. p16 may be useful to identify small focal high-grade CIN lesions, to distinguish some cases of CIN involving immature metaplastic squamous epithelium from immature metaplastic squamous epithelium not involved by CIN and to distinguish high-grade CIN from benign mimics. Most cervical carcinomas of squamous, glandular, and small cell type are p16-positive. In cervical glandular lesions, p16 is useful, as part of a panel, in the distinction between adenocarcinoma in situ (diffusely positive) and benign mimics, including tuboendometrial metaplasia and endometriosis, which are usually p16-negative or focally positive. p16 may be used, in combination with other markers, to distinguish between a cervical adenocarcinoma (diffuse positivity) and an endometrioid-type endometrial adenocarcinoma (negative or focally positive). Some uterine serous carcinomas are diffusely positive. In the vulva, p16 is positive in HPV-associated vulval intraepithelial neoplasia (VIN) but negative in VIN not associated with HPV. Similarly, HPV-associated invasive squamous carcinomas are p16-positive, whereas the more common non-HPV-associated neoplasms are largely negative or focally positive. In the uterus, p16 positivity is more common and widespread in leiomyosarcomas than leiomyomas, and this may be a useful aid to diagnosis, although problematic uterine smooth muscle neoplasms have not been extensively studied. Metastatic cervical adenocarcinomas in the ovary are usually diffusely p16-positive, and because these may closely mimic a primary ovarian endometrioid or mucinous adenocarcinoma, this may be a valuable diagnostic aid, although p16 expression in primary ovarian adenocarcinomas of these morphologic subtypes has not been widely investigated. Some ovarian serous carcinomas, similar to their uterine counterparts, are p16-positive.

Adenocarcinoma↗

Leiomyosarcoma of somatic soft tissues in childhood: an immunohistochemical analysis of six cases with ultrastructural correlation.

Leiomyosarcoma (LMS) of soft tissue is a rare tumor in children. Although LMS may exhibit clinical and histologic features that are typical of smooth muscle neoplasms in adults, they may often be confused with or resemble tumors of presumed fibroblastic, myofibroblastic, or rhabdomyoblastic differentiation. As a result, the diagnosis of LMS in children is often difficult to establish with confidence. To address this problem, we analyzed the immunohistochemical features of six LMS in children (one of deep soft tissue of an extremity, one of paravertebral tissue, one of the retroperitoneum, two of oropharyngeal soft tissue, and one of subcutis); the ultrastructural features of four of these tumors were also studied. Histologically, each of the three tumors of deep soft tissue and one of the retromolar trigone were composed of pleomorphic spindle cells arranged in interweaving fascicles. In contrast, the subcutaneous tumor and the lesion of the hard palate had an epithelioid appearance. Ultrastructural features were typical of adult type LMS. Immunohistochemically, these neoplasms were diffusely reactive for vimentin, while each was negative for cytokeratin, epithelial membrane antigen, and S-100 protein. Desmin was present in all cases, but was expressed only focally in three; a similar pattern of staining was noted for muscle-specific actin, although staining was generally noted in a larger population of cells. alpha-1-Antichymotrypsin was found in five tumors, and cathepsin B reactivity was encountered in four cases. Leu-7 antigen and myelin basic protein were coexpressed by one tumor, but neither was found in the remaining cases. These results indicate that immunohistochemical detection of desmin and muscle-specific actin may be useful in the differential diagnosis of spindle or epithelioid cell proliferations in childhood when ultrastructural analysis in unavailable.

Adolescent↗

Glomus coccygeum: report of a case and review of the literature.

The glomus coccygeum is a vestigial structure related to the canals of Sucquet-Hoyer, an arteriovenous anastomosis surrounded by glomus cells derived from modified smooth muscle and involved in thermoregulation. It is an incidental finding in specimens from the sacral area and may represent a diagnostic challenge to the unaware observer. We present a case of a glomus coccygeum, presenting as a 1.5-mm structure adjacent to a typical pilonidal cyst excised from a 7-month-old boy, which was the subject of a second opinion consultation. The lesion showed small to medium sized clusters of predominantly epithelioid cells with moderate amounts of clear to eosinophilic cytoplasm, intercellular borders, and plump, round nuclei with fine chromatin. These cells were closely associated with small vascular channels and nerves. Immunohistochemistry revealed that the epithelioid cells expressed vimentin, muscle-specific actin, neuron-specific enolase, and S-100 protein, were weakly positive for smooth muscle actin, and negative for desmin, synaptophysin, and chromogranin. The endothelial cells of the vascular channels were antibody CD31 positive. Recognition of the histologic features of glomus coccygeum is important to avoid confusion with glomus tumor and neural or smooth muscle neoplasms in the sacral area.

Arteriovenous Anastomosis↗