Angiocentric immunoproliferative lesion and angiocentric lymphoma of lymph node in children. A report of two cases.

AIM: To report two examples of an angiocentric immunoproliferative lesion (AIL) and angiocentric angiodestructive lymphoma (AL) presenting in lymph nodes in children. Most commonly involving extranodal sites, AIL/AL rarely presents in the spleen and lymph nodes. METHODS/RESULTS: Case 1 presented as a cervical lymphadenopathy in a 3 year old girl being treated for pre-B cell acute lymphoblastic leukaemia. Histological and immunohistochemistry studies revealed an Epstein-Barr virus positive (EBV+), large B cell (CD20 and CD30+) AIL with large areas of necrosis, the whole resembling lymphomatoid granulomatosis. Case 2 presented as a large supraclavicular lymphadenopathy in a 13 year old boy. Histology and immunohistochemistry revealed an EBV-, large T cell (CD45RO, CD56, and CD30+) AL, presenting the features of so called angiocentric T cell/natural killer cell lymphoma, nasal type. CONCLUSIONS: The term AIL/AL refers to a heterogeneous group of conditions not unique to a particular type of lymphoid cell. These lesions are easily recognised by the histopathologist because of their extremely unusual angiocentric pattern. Although rare, AIL/AL may present as nodal lesions in children ab initio.

Extracutaneous infantile haemangioma is also Glut1 positive.

AIM: To investigate whether extracutaneous infantile haemangioma-like tumours are immunohistochemically similar to cutaneous infantile haemangiomas. METHODS: Mammary, salivary gland, liver (one each), and placental (two cases) capillary haemangiomas and typical examples of cutaneous (eight cases) infantile haemangioma were investigated immunohistochemically for alpha smooth muscle actin and Glut1, a proposed marker for the skin localised lesion. Positive internal controls included red blood cells, perineurium, trophoblast, and endothelial cells of the placental capillaries. Extralesional vessel endothelium acted as a negative control (except in the placenta). The liver haemangioma and both chorioangiomas presented in patients with Beckwith-Wiedemann syndrome. RESULTS: The endothelial cells of all the vascular lesions were Glut1 positive. These were consistently surrounded by a rim of alpha smooth muscle actin positive pericytic cells. Controls reacted appropriately. CONCLUSIONS: All infantile haemangiomas were immunohistochemically positive for Glut1: expression of this molecule was not limited to infantile haemangiomas of the skin. These tumours comprise proliferations of both endothelial and pericytic cells. The association with Beckwith-Wiedemann syndrome may provide a clue to the molecular genetics of infantile haemangioma.

Metastatic metanephric adenoma with foci of papillary carcinoma in a child: a combined histologic, immunohistochemical, and FISH study.

We report an example of metastatic metanephric adenoma containing foci of papillary carcinoma in the primitive tumor arising in the left kidney of an 11-year-old girl. Histology revealed a monomorphous population of small cells with bland cytology arranged in pseudoglandular, tubular, papillary, and glomeruloid structures with frequent psammoma bodies. Intermixed there were foci of and small cavities lined by larger cells with eosinophilic cytoplasm and larger nuclei with small nucleoli. A regional lymph node contained metastatic deposits with the former histologic pattern. By immunohistochemistry the small cells were negative for carcinoembryonic antigen (CEA) and keratin 7 while these antibodies reacted positively in the larger cells. A fluorescent in-situ hybridization (FISH) study for chromosome 17 in imprints from the primitive tumor revealed 3 signals in about 10% of the nuclei while the rest was disomic. Disaggregated cells from the metastatic lymph node consistently revealed 2 signals for chromosomes 7, 16, and l7. Histology of the primitive tumor resembled the epithelial component of the so-called metanephric adenofibroma while the metastatic lymph node exhibited histologic and FISH genomic features of metanephic adenoma. Int J Surg Pathol 9(3):241-247, 2001

Primary angiocentric T-cell intestinal lymphoma with Epstein-Barr virus in a 5-year-old boy.

A case of peripheral T-cell lymphoma affecting the small bowel of a 5-year-old boy is reported. The cells did not form a tumoral mass but infiltrated diffusely, arranged in an angiocentric pattern and associated with numerous ulcers, one of which perforated. Immunohistochemistry proved them to be CD45RO-, CD3-, and CD8-positive. CD20, CD4, and CD56 markers were negative. The presence of EBV in the lymphomatous cells was demonstrated by in-situ hybridization. Polymerase chain reaction study revealed T-cell receptor (TCR) gene rearrangement. Notably the hemophagocytic syndrome present on admission reverted after surgery. The authors are not aware of a previous report of intestinal T-cell lymphoma in a child.

Lymphohistiocytic and granulomatous phlebitis in penile lichen sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory disease of unknown etiology that may affect the genital and/or extragenital skin of individuals of either sex at all ages. In boys, the prepuce is the most common site of involvement. The diagnostic criteria of LS include the presence of inflammatory infiltrates mainly composed of T lymphocytes. We report on two cases of LS of the prepuce because of the unusual feature of lymphocytic (CD45RO+ and CD20+), histiocytic (CD68+), and granulomatous phlebitis. This lesion was not present in a group of another 18 cases of childhood penile LS. We have not been able to find any references describing and illustrating inflammatory involvement of the dermal vein walls in LS. Unlike the data reported in the literature, the dermal inflammatory infiltrates of these two cases showed a similar proportion of B and T lymphocytes in addition to frequent CD68+ histiocytes.

Association of sympathomimetic drugs with malformations.

We observed 2 cases of severe limb defects in infants following the use of sympathomimetic drugs during pregnancy. The mother of I had taken large doses of Primatene (ephedrine, theophylline, phenobarbital) as tablets and mist throughout pregnancy. The infant was born with oligoectrosyndactyly. In the other infant, maternal ingestion of sympathomimetic drugs including Triaminic (pseudoephedrine, phenylephrine, phenylpropanolamine) was associated with distal limb defects. Experimental studies in pregnant rabbits using Primatene in both low and high dosage resulted in limb reduction defects and other malformations in a significant number of the offspring compared with controls. Limb defects in the offspring of chicks following exposure to sympathomimetic drugs had previously been observed. We suggest that these agents may be teratogenic in the human and should be used with great caution or avoided during pregnancy.

Solitary unilocular cyst of the lung with features of persistent interstitial pulmonary emphysema: report of four cases.

Neonatal interstitial pulmonary emphysema (IPE) is a well-characterized lesion usually presenting in preterm newborns as a complication of respiratory distress syndrome and/or assisted ventilation. Occasionally, IPE may occur spontaneously in infants with no underlying pulmonary disease. Persistence of IPE (PIPE) may be diffuse or localized. Localized PIPE usually presents as multiple cysts 0.3 to 3 cm in one or more lobes of the lung. In this report, we describe four cases of unilocular large cysts (up to 5 cm in diameter) partially lined by uni- and multinucleated histiocytes in a foreign body type reaction and showing gas dissection of the surrounding parenchyma (present in case 1). These histological features favored the diagnosis of PIPE and the cases were interpreted as such, since no other clear-cut diagnosis could be defined. However, because the lesion was limited to one lobe, and the children were full term, asymptomatic at birth and without history of respiratory distress or assisted ventilation, differential diagnosis with other pulmonary cystic lesions of infancy is mandated.

Adnexal-centered giant congenital melanocyte nevus with extensive ganglioneuromatous component and trisomy 7.

Adequate interpretation of clinical and histopathologic features of giant congenital melanocytic nevus (GCMN) in newborns is a continued challenge. A GCMN with three large nodules and three polypoid exophytic tumors presented in the dorsum of a female full-term newborn, the borders exhibiting a spotted grouped pattern. Microscopic examination revealed a peculiar adnexal-centered (eccrine sweat gland ducts, acrosiringia, and hair infundibula) compound nevus expressing pagetoid intraepidermal spreading of epithelioid melanocytes. The nodules represented an extensive ganglioneuromatous component. The neurons and their neuropil were positive for neuron-specific enolase, S-100, synaptophysin, tyrosine hydroxilase, and PGP 9.5. In addition to these components, a poorly differentiated, fusiform, low-mitotic rate population of cells undergoing epithelioid differentiation (and probably neuronal differentiation) with nodular arrangement was also present in the polypoid tumors and deeper parts of the nevus, in part intermixed with the neurons. These cells were vimentin positive but S-100 negative. FISH studies revealed these cells to express three signals for the centromeric probe for chromosome 7 whereas the neuronal component showed just two. Adnexal-centered arrangement of melanocytes has not been emphasized in GCMN. Ganglioneuromatous differentiation has been rarely reported in this condition. Trisomy 7 in GCMN has been reported only once previously.

Massive myocardial calcification in the perinatal period.

Massive myocardial calcification (MMC) in the perinatal period is an unusual finding considered to be a unique tissue reaction. This report summarizes the clinical and pathologic findings of seven cases of perinatal MMC. All patients presented clinical evidence of myocardial damage. In two cases arrhythmia was detected in utero. Four cases presented with hydrops, one of which was associated with major heart malformation. One case was a trisomy 13. Three cases had polyhydramnios. Our results demonstrate that calcification follows progressive stages from patches of calcified myocardial cells (stage I), to coagulative and colliquative myocytolysis with clusters of interstitial mononucleated cells (stage II), to collapsing fibrosis with granulation tissue and multinucleated regenerative myocardial cells (stage III), and finally to fibrous scars containing entrapped remaining myocardial cells (stage IV). Literature review and our findings suggest that perinatal MMC results from different conditions inducing hypoxic-ischemic damage that later is followed by progressive scarring if the patient survives the acute stage. The lesion may represent the human counterpart of the so-called dystrophic cardiac calcinosis in mice. This disease is related to an abnormality at the Dyscalc locus of proximal chromosome 7 (syntenic with human chromosome 19q13 and 11p15).

Yolk sac tumor of the placenta in Wiedemann-Beckwith syndrome.

The present report describes an example of multifocal (two) yolk sac tumor (YST) with mesenchyme-like and enteroid patterns found in the placenta (730 g) of a newborn (4200 g) with Wiedemann-Beckwith syndrome (WBS) phenotype (macroglossia, omphalocele, hemihypertrophy, cardiomegaly, hypoglycemia). YST has not been previously reported to develop in the placenta. This case expands further the spectrum of alterations found in the placenta in the WBS and fits in the list of tumors related to WBS. ¿KW¿

Presence of human papillomavirus in extrahepatic biliary atresia.

BACKGROUND: In a previous study the human papillomavirus DNA was detected in seven cases of so-called idiopathic neonatal giant cell hepatitis by using nested polymerase chain reaction. The purpose of the present study was to study the prevalence and possible common causes of human papillomavirus-associated idiopathic neonatal giant cell hepatitis and extrahepatic biliary atresia. METHODS: Formalin-fixed, paraffin-embedded archival tissues obtained in 18 cases of extrahepatic biliary atresia were studied for human papillomavirus DNA by nested polymerase chain reaction. In addition, in situ hybridization was performed on tissue obtained in 6 cases. RESULTS: Tissue in 16 of the 18 cases studied showed amplified human papillomavirus DNA, whereas no human papillomavirus was amplified in any of 30 control samples. Main human papillomaviruses detected were types 6 and 18. Punctate intranuclear positive signals were detected in the hepatocytes after in situ hybridization for human papillomavirus DNA. CONCLUSIONS: The high prevalence of human papillomavirus DNA in liver tissue in cases of extrahepatic biliary atresia suggests a strong correlation between this disorder and idiopathic neonatal giant cell hepatitis. It further suggests that this virus may be one of the causative agents in extrahepatic biliary atresia and may represent part of the spectrum of lesions associated with neonatal human papillomavirus-induced hepatic damage.

[Human papillomavirus, neonatal giant cell hepatitis and biliary duct atresia]. / Virus papiloma humano, hepatitis gigantocelular neonatal y atresia de vías biliares.

We previously recognized the presence of HPV-DNA in cases of idiopathic neonatal giant cell hepatitis (INGCH) and extrahepatic biliary duct atresia (EBDA) in archivated tissue using the PCR technique. In order to investigate a possible vertical transmission we looked for the presence of HPV-DNA in cervical swabs in the mothers along with formalin-fixed paraffin-embedded hepatic tissue from 3 infants with INGCH and 4 patients with EBDA by nested-PCR. Cervical smears showed koilocytosis consistent with HPV infection in 2 cases. Delivery was vaginal except for one that was by cesarean section. All infants were males. Amplification of HPV-DNA was demonstrated in all cases, the types being concordant in infants and mothers. Although this is a small group, the findings appear in line with previous data. The presence of the same type of HPV-DNA in the infants' livers and their mothers' cervical swabs is another argument supporting the possibility of vertical transmission of the virus.

Human papillomavirus is present in some cases of childhood penile lichen sclerosus: an in situ hybridization and SP-PCR study.

Lichen sclerosus (LS) is a skin disease that may affect both sexes at all ages and at any site. Its etiology remains unknown. The observation of focal koilocytotic-like changes in the stratum malpighii in prepuce samples of LS in children prompted us to investigate the presence of HPV-DNA. Twenty-three paraffin-embedded samples of LS lesions from children aged 4 to 14 years were studied using nested-PCR and in situ hybridization (ISH). Twelve out of 23 cases amplified HPV-DNA (8 cases corresponded to HPV-DNA type 6; 2 cases each to HPV-DNA types 16 and 18). ISH detected HPV sequences in the nuclei of koilocytotic and some parakeratotic cells in 13 cases (9/13 also HPV-DNA positive by PCR). Our results demonstrated the presence of HPV-DNA in roughly 70% of cases of LS of the prepuce in children. We highlight the observation of koilocytotic-like changes in the prepuce and its association with HPV. The possible pathogenetic significance between the virus and the lesion is not settled.

Human papillomavirus (HPV)-associated neonatal giant cell hepatitis (NGCH).

Neonatal giant cell hepatitis (NGCH) is a clinicopathological syndrome that has been related to perinatal infections and metabolic disorders. In a great number of cases no apparent etiology has been found. To characterize the possible relationship between human papillomavirus (HPV) and idiopathic NGCH (INGCH) we analyzed paraffin-embedded hepatic biopsies from seven cases of INGCH for the presence of both HPV and cytomegalovirus (CMV) DNA. Clinically, jaundice, detected within the first 3 days of life (except in one case), and raised levels of serum transaminases and bilirubin, mainly the direct fraction, were recorded in all. Follow-up of six patients revealed complete recovery. In a "blind" experiment, samples were studied along with appropriate controls [2 cases of CMV hepatitis, one case of postinfantile GCH, 12 cases of juvenile laryngeal papillomatosis (JLP), and 5 normal neonatal liver samples] by polymerase chain reaction (PCR). All DNA samples from INGCH consistently showed positive HPV DNA amplification. This was also found in the samples from postinfantile GCH and JLP. In addition, a second biopsy performed 11 months later in one of the cases of INGCH revealed scattered multinucleated hepatocytes and was still positive for HPV DNA. CMV-DNA was detected only in the cases of CMV hepatitis. All five normal livers were negative for HPV and CMV-DNA. These data seem to indicate that HPV may be closely related to a subset of "idiopathic" NGCH with good outcome.

Nonimmune fetal hydrops and placentomegaly: diagnosis of familial Wiedemann-Beckwith syndrome with trisomy 11p15 using FISH.

We have studied a family in which four members of the same generation were affected with Wiedemann-Beckwith syndrome (WBS). Trisomy 11p15 was demonstrated using molecular probes in interphase nuclei of formalin-fixed paraffin-embedded placenta from a stillborn fetus and in peripheral blood lymphocytes from two liveborn female relatives. Clinical examination showed nonimmune hydrops and placentomegaly in two siblings and multiple phenotypic abnormalities consistent with WBS in the two other relatives. Paternal karyotype of the stillborn infants demonstrated a reciprocal translocation (46,XY,t(10;11) (q26;p15)) explaining the origin of the extra 11p15 material. This study illustrates the advantages of FISH for interphase analysis of chromosome aberrations otherwise not detected even by conventional cytogenetic analysis and documents that nonimmune hydrops associated with placentomegaly may be the presenting features in familial WBS.

Cytomegalovirus-associated Ménétrier's disease in adults. Demonstration by polymerase chain reaction (PCR).

Ménétrier's disease (MD) is a rare form of hypertrophic or hyperplastic gastropathy characterized by conspicuous thickening of the gastric mucosal folds and foveolar (crypt) hyperplasia. We examined the presence of cytomegalovirus (CMV) in 2 cases of MD in adults, one associated with gastric carcinoma, using the polymerase chain reaction (PCR). None of the cases showed intranuclear inclusions consistent with CMV infection. Both revealed, besides the features of MD, a peculiar pattern of "chronic active plasmacellular gastritis". Although the samples had been stored in formalin for more than 10 years CMV-DNA was recovered with good yield from both samples. The demonstration of CMV in MD in adults may helps to explain present knowledge of the complex relationships between this virus and gastric mucosa, and strongly suggests a pathogenetic role of the virus with variable phenotypic expression along the years.

Detection of human papillomavirus in juvenile laryngeal papillomatosis using polymerase chain reaction.

We examined the presence and subtypes of human papillomavirus (HPV) in 20 paraffin-embedded samples (from 12 patients) of juvenile laryngeal papillomatosis using the polymerase chain reaction (PCR). The biopsies had been stored for months to 12 years. Due to the great genetic variability of HPV, we selected a conservative sequence of the viral genome (L1 region) to identify the vast majority of the subtypes. Positive results were obtained by one-step PCR amplification with the MY09-11 consensus primers (L1 region) in only 10 of the cases. After a two-step amplification (nested-PCR) with GP5-6 primers the 20 samples proved to be positive demonstrating the higher sensitivity of this method. In order to amplify a highly variable region of the genome (E6), specific primers for HPV types 6 and 11 (H6/11 L1-R2) were used. 7/12 patients were positive for this subtype. Since more that one subtype has been reported in the same sample, the presence of HPV 6-11 sequences does not exclude that other subtypes might be involved. The results of this study show that: 1) HPV is present in JLP. 2) The most frequent HPV subtype involved was from the 6-11 group. 3) PCR can be successfully used in archived tissue routinely processed in a laboratory of pathology.

Detection of human papillomavirus in juvenile laryngeal papillomatosis using polymerase chain reaction.

We examined the presence and subtypes of human papillomavirus (HPV) in 20 paraffin-embedded samples (from 12 patients) of juvenile laryngeal papillomatosis using the polymerase chain reaction (PCR). The biopsies had been stored for months to 12 years. Due to the great genetic variability of HPV, we selected a conservative sequence of the viral genome (L1 region) to identify the vast majority of the subtypes. Positive results were obtained by one-step PCR amplification with the MY09-11 consensus primers (L1 region) in only 10 of the cases. After a two-step amplification (nested-PCR) with GP5-6 primers the 20 samples proved to be positive demonstrating the higher sensitivity of this method. In order to amplify a highly variable region of the genome (E6), specific primers for HPV types 6 and 11 (H6/11 L1-R2) were used. 7/12 patients were positive for this subtype. Since more that one subtype has been reported in the same sample, the presence of HPV 6-11 sequences does not exclude that other subtypes might be involved. The results of this study show that: 1) HPV is present in JLP. 2) The most frequent HPV subtype involved was from the 6-11 group. 3) PCR can be successfully used in archived tissue routinely processed in a laboratory of pathology.

Cytomegalovirus-associated Ménétriers disease in adults. Demonstration by polymerase chain reaction (PCR).

Ménétriers disease (MD) is a rare form of hypertrophic or hyperplastic gastropathy characterized by conspicuous thickening of the gastric mucosal folds and foveolar (crypt) hyperplasia. We examined the presence of cytomegalovirus (CMV) in 2 cases of MD in adults, one associated with gastric carcinoma, using the polymerase chain reaction (PCR). None of the cases showed intranuclear inclusions consistent with CMV infection. Both revealed, besides the features of MD, a peculiar pattern of [quot ]chronic active plasmacellular gastritis[quot ]. Although the samples had been stored in formalin for more than 10 years CMV-DNA was recovered with good yield from both samples. The demonstration of CMV in MD in adults may helps to explain present knowledge of the complex relationships between this virus and gastric mucosa, and strongly suggests a pathogenetic role of the virus with variable phenotypic expression along the years.

EBV-associated Kaposi's sarcoma in a pediatric renal transplant recipient.

A 7-year-old boy had undergone kidney transplantation for chronic renal failure secondary to bilateral renal hypoplasia. He developed acute and chronic rejection and received immunosuppressive therapy. A year later he died with EBV-associated hemophagocytic syndrome. The main pathologic findings disclosed visceral (lung and stomach) and abdominal lymph node involvement of Kaposi's sarcoma and EBV-positive immunoblasts in several organs. In the lungs and lymph nodes these had the features of polymorphous lymphoimmunoblastic lesions. Because of the peculiar distribution of Kaposi's sarcoma lesions a pathogenetic hypothesis is proposed based on the site of entry of the virus. This case contributes to expanding the relationship between Kaposi's sarcoma and kidney transplantation in the pediatric population.