Pulmonary vein stenosis: expression of receptor tyrosine kinases by lesional cells.

BACKGROUND: Primary pulmonary vein stenosis (PVS) is a progressive disorder of infants. Although catheter based intervention and chemotherapy are used to manage the disorder, the benefit of these approaches is reduced considerably by restenosis. The nature of the intimal cells causing the occlusive lesions in PVS is poorly understood. METHODS: Seven PVS cases were studied with antibodies for smooth muscle actin (SMA), muscle-specific actin (MSA), monoclonal desmin, S100 protein, CD31, CD34, CD45RO, CD68, CD99, Ki-67 (MIB-I), and with antibodies directed against several receptor tyrosine kinases (RTK), including platelet-derived growth factor alpha and beta receptor (PDGFR-alpha and -beta), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor 1 and 2 receptor (VEGFR), and stem cell factor receptor (c-kit). RESULTS: Lesional cells stained strongly and diffusely with SMA and MSA, but not for macrophage, lymphocyte, endothelial markers, or for Ki-67. RTK expression was strong and diffuse for PDGFR-alpha and -beta, FGFR, and VEGFR-2. Lesional cells stained for VEGF and PDGF beta receptor was phosphorylated. CONCLUSIONS: The histologic appearance, and the strong diffuse immunoreactivity for smooth muscle markers, indicates that the intimal lesional cells are myofibroblast-like. Expression of various receptor tyrosine kinases and some ligands suggests an autocrine or paracrine role of these proteins in the pathogenesis of the intimal occlusive lesion in PVS.

Primary thyroid teratomas in children: a report of 11 cases with a proposal of criteria for their diagnosis.

Cervical teratomas are uncommon neoplasms, although the commonest neck tumors in newborns and infants. Presence of associated thyroid tissue often causes speculation as to the site of origin, ie, arising from within thyroid, adjacent soft tissue with secondary involvement of thyroid, or as innate part of a cervical teratoma. Twenty-eight cases of cervical teratomas were identified over 75 years, including 11 cases containing associated thyroid tissue. Clinical history, treatment, and follow-up were reviewed and the neoplasms analyzed regarding location, size, degree of maturity, and relative arrangement of thyroid and other tissues. All thyroid teratomas were congenital, measured 3.5 to 13.5 cm in diameter (median size, 6.9 cm), and were resected. Follow-up ranged from 1 to 45 years (median, 17 years) without recurrent disease in any patient. Neuroglial tissue predominated in 10 of 11 tumors. Intimate admixture of thyroid and other tissues with or without surrounding fibrous pseudocapsule was present in 8 cases, suggesting thyroid as origin. Histologic immaturity in congenital thyroid teratomas is not the harbinger of adverse behavior as seen in adolescents and adults. Intimate intermingling of thyroid tissue with teratoma and presence of a pseudocapsule seem to be the most significant criteria for establishing thyroid as origin.

Mucoepidermoid carcinoma of the skin: a distinct entity from adenosquamous carcinoma: a case study with a review of the literature.

Mucoepidermoid carcinoma (MEC) of the skin is an exceedingly rare but distinctive neoplasm with respect to its histopathologic features. It is similar if not identical in most respects to MEC of the salivary gland, a neoplasm whose prognosis is correlated with the pathologic grade. We report a case of MEC of the skin in a 79-year-old white woman who presented with an axillary mass. Beneath an unremarkable epidermis, a circumscribed, cystic neoplasm, unattached to the surface, was characterized by the presence of vague lobules of low-grade-appearing squamous cells accompanied by mucigenic and clear cells. A mucin stain highlighted the mucigenic cells and immunohistochemistry revealed pan-cytokeratin, cytokeratin 7, polyclonal carcinoembryonic antigen, and epithelial membrane antigen positivity. The cytokeratin 20 and gross cystic disease fluid protein were nonreactive. Inconsistency was encountered in the literature where some confusion existed as to whether MEC is synonymous with adenosquamous carcinoma of the skin. Elsewhere in the body, the latter tumor type is a squamous and gland-forming neoplasm with intermediate- to high-grade features rather than a tumor with mucigenic cells intermingled among intermediate and squamous cells. As in the case of MEC and adenosquamous carcinoma elsewhere in extracutaneous sites, we would propose that a pathologic distinction should be made in the skin for the sake of consistency and for prognostic purposes. Additionally, the immunophenotype of our case is similar to at least two other cases of cutaneous MEC, as well as MEC of the salivary gland, to support the hypothesis that this neoplasm is adnexal rather than epidermal in origin.

Tumefactive necrobiotic granulomas (nodulosis) of the pancreas in an adult with long-standing rheumatoid arthritis.

Rheumatoid nodules are well-documented clinical and pathologic lesions in patients with seropositive rheumatoid arthritis (RA). The current report documents the occurrence of rheumatoid nodulosis of the pancreas in an adult woman with a 7-year history of seropositive RA who presented with upper abdominal pain and was found to have multiple masses in the body and tail of the pancreas by imaging studies. An elevated serum pancreatic polypeptide (PP) and the development of new lesions in the pancreas prompted a subsequent distal pancreatectomy. The lesions in the pancreas proved to be necrobiotic palisading and hyalinizing granulomas upon pathologic examination. Also, of interest, elevation of serum PP has been observed in patients with RA and other systemic noninfectious and infectious inflammatory disorders in the absence of a pancreatic or intestinal neuroendocrine neoplasm.

Uncommon synchronous association between ovarian carcinoma and gastrointestinal stromal tumor: a case study and literature review.

BACKGROUND: The association of gastrointestinal stromal tumors (GIST) and other cancers is well known, but its synchronous occurrence with gynecological malignancies is very uncommon. Usually, the diagnosis is accidentally established. We describe a patient with GIST and concurrent ovarian cancer and discuss the clinical implications of this finding. CASE REPORT: A 64-year-old woman with a prior diagnosis of ovarian cancer developed a second recurrence after having undergone two operations and adjuvant chemotherapy. While tumor debulking was performed, a small, nonsuspicious lesion was removed from the greater curvature of the stomach. Histology revealed a GIST. CONCLUSION: The association of GIST and ovarian cancer is a rarity and its synchronicity may alter the oncological prognosis and therapy of the patient.

Immunohistochemical evaluation of endometriotic lesions and disseminated endometriosis-like cells in incidental lymph nodes of patients with endometriosis.

OBJECTIVE: To investigate the frequency of endometriotic lesions and disseminated endometriotic-like cells in a series of incidentally removed lymph nodes (LNs) in patients with endometriosis. DESIGN: Retrospective study. SETTING: University hospital endometriosis center. PATIENT(S): Premenopausal patients underwent surgery because of endometriosis-associated symptoms. INTERVENTION(S): Retrospective analysis of 108 coincidentally resected LNs of 24 patients with endometriosis. To identify endometriotic cells, immunohistochemical analysis of estrogen and progestogen receptor (ER-PR), CD10, and cytokeratin was performed. MEAN OUTCOME MEASURE(S): The occurrence of endometriotic lesions (ER-PR, CD10, and cytokeratin positive) and disseminated endometriotic-like ER-PR-positive cells in LNs. RESULT(S): Deep infiltrating endometriosis was diagnosed in 23 of the 24 patients with incidentally removed LNs. In 8 of 24 (33.3%) patients with incidentally removed LNs, typical endometriotic lesions were detected. Disseminated ER-PR-positive cells were found in 17 of 24 patients (70.8%). Lymph node involvement correlated directly with the deep infiltrating endometriosis lesional size. CONCLUSION(S): Estrogen receptor-progestogen receptor-positive endometriotic lesions and disseminated endometriotic-like cells frequently are detected in LNs of patients with deep infiltrating endometriosis and, therefore, might reflect "nonlocalized" disease. If clinical significance of such lesions were provided, adjuvant hormonal treatment could be considered as a possible additional mode of therapy.

Solid extratesticular masses in children: radiographic and pathologic correlation.

OBJECTIVE: The purpose of this pictorial essay is to review the sonographic and pathologic appearances of the most common solid and complex extratesticular masses in children. CONCLUSION: Solid or complex extratesticular masses, especially those that are rapidly growing and are painless, raise concerns regarding malignant rhabdomyosarcoma. Mimickers of rhabdomyosarcoma include inflammatory processes such as pseudotumor, chronic epididymitis, or meconium periorchitis. Because sonography cannot distinguish benign from malignant, worrisome extratesticular masses should be biopsied or removed.

Bronchial atresia is common to extralobar sequestration, intralobar sequestration, congenital cystic adenomatoid malformation, and lobar emphysema.

Congenital cystic adenomatoid malformation (CCAM), intralobar sequestration (ILS), extralobar sequestration (ELS), and lobar emphysema (LE) are well-accepted entities; however, certain findings are common to all, particularly the parenchymal maldevelopment characterizing CCAM. Isolated reports have described bronchial atresia (BA) in some specimens in all 4 entities, but this finding has not been evaluated in a prospective manner. With the aid of a dissecting microscope, we prospectively examined 47 lung specimens resected during the past 4 years and submitted with the clinical impression of ELS (n=11), ILS (n=11), CCAM (n=20), LE (n=4), and airway-esophageal communication (n=1). Most lesions were detected by prenatal ultrasound and were resected during infancy. The clinical impression and pathologic findings were compared. Pathologic examination revealed atresia of a lobar, segmental, or subsegmental bronchus in 100% of ELS, 82% of ILS, 70% of CCAM, and 50% of LE (those clinically recognized to have BA or minor CCAM) cases. Parenchymal maldevelopment that characterizes CCAM was present in 100% of CCAM cases (as expected by definition) as well as in 91% of ELS, 91% of ILS, and 50% of LE (those with BA) cases. Bronchial atresia is present in all ELS, most ILS and CCAM, and some LE cases, and its detection is greatly enhanced with the dissecting microscope. Bronchial atresia and CCAM nearly always coexist. It may be that both have the same etiopathogenesis with anatomic differences accounted for by aberrant genetic programs or other insults, perhaps modified by time of onset or duration.

Primary sclerosing cholangitis in children and adolescents: a clinicopathologic study with a proposal of criteria for early diagnosis / Colangite esclerosante primária em crianças e adolescentes: uma correlação clinicopatológica com uma proposta de critérios para primeiro diagnóstico

INTRODUCTION: Primary sclerosing cholangitis (PSC) has been increasingly diagnosed among children and adolescents due to better recognition of clinical, imaging and pathological features. Thus more patients are diagnosed at a younger age due to imaging and sensitivity optimization. OBJECTIVE: Early liver histopathological (LH) changes are not well described and PSC is not commonly recognized before typical bile duct changes occur on cholangiography (CG). Currently, CG is considered gold standard for adults but nothing is known for early diagnosis in the pediatric age group (0- 20 years old). METHODS: We reviewed clinical history, LH and CG from 47 children and adolescents with PSC (35 males, mean age 13 years old). Forty-three out of 47 patients had been through LH examination from whom 33 had also undergone CG. A clinicopathological correlation was performed. RESULTS: LH showed active neutrophilic cholangitis in 19 patients, moderate neutrophilic pericholangitis in nine, dystrophic changes in the bile duct in eight, and concentric periductal fibrosis in 24 patients. Abnormal CG was found in 24 out of 33 patients and nine had normal results. Eleven out of these 24 patients had abnormal histology before abnormal CG and four patients had abnormal CG before histology. Data of two out of 24 patients were insufficient for correlation and 11 out of 24 had both abnormal liver histology and abnormal imaging findings. CONCLUSION: Our study emphasizes that even when CG is normal, PSC should be exclusively diagnosed by liver biopsy, hence cholangiography being unnecessary. Chronic portal inflammation, neutrophilic pericholangitis, periductal sclerosis and "onion skinning" are characteristic histopathological findings. Neutrophilic pericholangitis may be subtle and easily overlooked in early disease, leading to strong suspicion of PSC.

INTRODUÇÃO: Colangite esclerosante primária (CEP) é crescentemente diagnosticada em crianças e adolescentes devido ao melhor reconhecimento das apresentações clínicas por imagem e manifestações patológicas. Devido a isso, aumentaram a sensibilização e a melhora das imagens e, cada vez mais, os pacientes são diagnosticados em idade mais jovem. OBJETIVO: As primeiras mudanças na histopatologia do fígado (HF) não são bem descritas e a CEP não é frequentemente reconhecida antes da típica mudança do ducto biliar ocorrer na colangiografia (CG). Atualmente, a CG é considerada padrão-ouro em adultos, mas nada é conhecido para o diagnóstico precoce na faixa etária pediátrica (0-20 anos de idade). Métodos: Nós revisamos histórico clínico, HF e CG de 47 crianças e adolescentes com CEP (35 meninos, idade média de 13 anos). Desses, 43 tinham HF, sendo que 33 também possuíam CG. Uma correlação clinicopatológica foi performada. RESULTADOS: HF mostrou colangite neutrofílica ativa em 19 pacientes, pericolangite neutrofílica moderada em nove, mudança distrófica do ducto biliar em oito e fibrose periductal concêntrica em 24. Um CG anormal foi constatado em 24/33; resultados de nove pacientes eram normais. Desses 24 pacientes, 11 tiveram histologia anormal de fígado antes da CG anormal e quatro apresentaram a situação inversa. Dados disponíveis de dois pacientes eram insuficientes para propósitos de correlação e outros 11 apresentavam, ao mesmo tempo, histologia anormal de fígado e resultados anormais de imagens. CONCLUSÃO: Nosso estudo enfatiza que a CEP pode ser exclusivamente diagnosticada por biópsia de fígado, sem colangiograma necessário ou mesmo no contexto de um CG normal. Inflamação portal crônica, pericolangite neutrofílica, esclerose periductal e "cebola esfolando" são resultados característicos de achados histopatológicos. A pericolangite neutrofílica pode ser sutil e facilmente negligenciada em doença precoce, requerendo alta suspeita para CEP.

Myogenic markers in the evaluation of embryonal botryoid rhabdomyosarcoma of the female genital tract.

Rhabdomyosarcoma presents special diagnostic problems when it involves the uterine cervix in young children because tumor cells may lack marked atypia and may blend with the normal, immature, condensed, cellular stroma, rendering diagnosis difficult. Myogenic makers are a valuable ancillary technique for establishing a diagnosis of rhabdomyosarcoma. However, desmin positivity has been reported in cervical stromal cells, which can confound diagnosis. To determine whether immunohistochemical markers of skeletal muscle differentiation are helpful in the diagnosis of uterine botryoid rhabdomyosarcoma, we compared the immunohistochemical staining pattern of cervical rhabdomyosarcoma from 3 patients with that of normal uteri from age-matched autopsy controls by using antibodies for desmin, smooth muscle actin, muscle-specific actin, myoD1, myogenin, and WT-1. All tumors demonstrated at least focal immunopositivity for desmin, muscle-specific actin, smooth muscle actin, myoD1, and WT-1, and 1 tumor was also positive for myogenin. Autopsy controls showed only scattered subepithelial stromal immunoreactivity for desmin, muscle-specific actin, smooth muscle actin, and WT-1 and showed cytoplasmic, but not nuclear, immunopositivity for myoD1 and myogenin. Myometrium was diffusely positive for desmin and muscle-specific actin. We conclude that desmin, muscle-specific actin, smooth muscle actin, and WT1 are not specific for discriminating embryonal rhabdomyosarcoma from normal subepithelial cells in the female genital tract of children, although the number of immunopositive cells is consistently larger in rhabdomyosarcoma. Nuclear staining for myoD1 and myogenin appears not to occur in normal tissue, but it may be absent or sparse in embryonal rhabdomyosarcoma. Our findings indicate that, in this anatomic site, the diagnosis of rhabdomyosarcoma and in particular determination of tumor margins remain very reliant on histomorphology.

Myogenic markers in the evaluation of embryonal botryoid rhabdomyosarcoma of the female genital tract.

Rhabdomyosarcoma presents special diagnostic problems when it involves the uterine cervix in young children because tumor cells may lack marked atypia and may blend with the normal, immature, condensed, cellular stroma, rendering diagnosis difficult. Myogenic makers are a valuable ancillary technique for establishing a diagnosis of rhabdomyosarcoma. However, desmin positivity has been reported in cervical stromal cells, which can confound diagnosis. To determine whether immunohistochemical markers of skeletal muscle differentiation are helpful in the diagnosis of uterine botryoid rhabdomyosarcoma, we compared the immunohistochemical staining pattern of cervical rhabdomyosarcoma from 3 patients with that of normal uteri from age-matched autopsy controls by using antibodies for desmin, smooth muscle actin, muscle-specific actin, myoD1, myogenin, and WT-1. All tumors demonstrated at least focal immunopositivity for desmin, muscle-specific actin, smooth muscle actin, myoD1, and WT-1, and 1 tumor was also positive for myogenin. Autopsy controls showed only scattered subepithelial stromal immunoreactivity for desmin, muscle-specific actin, smooth muscle actin, and WT-1 and showed cytoplasmic, but not nuclear, immunopositivity for myoD1 and myogenin. Myometrium was diffusely positive for desmin and muscle-specific actin. We conclude that desmin, muscle-specific actin, smooth muscle actin, and WT1 are not specific for discriminating embryonal rhabdomyosarcoma from normal subepithelial cells in the female genital tract of children, although the number of immunopositive cells is consistently larger in rhabdomyosarcoma. Nuclear staining for myoD1 and myogenin appears not to occur in normal tissue, but it may be absent or sparse in embryonal rhabdomyosarcoma. Our findings indicate that, in this anatomic site, the diagnosis of rhabdomyosarcoma and in particular determination of tumor margins remain very reliant on histomorphology.

Congenital bilateral renal arteriovenous malformation: an unrecognized cause of renal failure.

Congenital renal arteriovenous malformations (AVM) are very rare abnormal communications between arteries and veins. These lesions are almost always unilateral, predominantly in the right kidney, and usually asymptomatic until adulthood. We present a unique case of bilateral renal AVM in a 10-year-old white boy who developed renal failure requiring renal transplantation. Microscopic sections of an atrophic right and a slightly larger left kidney with tortuous and dilated hilar vessels showed elaborate derangement of arteries and veins insinuating between lobules. Glomeruli were diffusely enlarged with increased number of capillary loops. Glomerular basement membrane reduplication and fibrinoid necrosis was focally noted. Electron microscopy demonstrated absence of electron-dense deposits or mesangial interposition excluding membranoproliferative glomerulonephritis. We believe that the glomerular lesions are secondary to congenital renal arteriovenous malformation. To our knowledge, bilateral arteriovenous malformation in infancy is not previously described.