Juvenile xanthogranuloma. Ultrastructural and immunocytochemical studies

Morphologic features of three cases of juvenile xanthogranuloma (JXG) were consistent with the current concept of a benign process, although the lesion in one case grew steadily to an extensively infiltrating large mass, which clinically suggested a malignant growth. Ultrastructurally, the lesion consisted of morphologically different developmental stages of histiocytes, probably reflecting different functional levels. An interesting finding was the presence of occasional subplasmalemmal linear densities between these cells. These densities were at times symmetrically opposed, forming desmosomelike junctional complexes. Immunohistochemical study for the presence of lysozyme, alpha 1-antitrypsin, and S100 protein by the avidin-biotin-peroxidase complex was performed in all three cases. All immunostains were negative except the positive lysozyme stain in two cases. The ultrastructural and cytochemical characteristics of histiocytes in JXG were similar to epithelioid cells in the lymph node, suggesting that JXG is a reactive lesion.     

Juvenile xanthogranuloma of the nasal cavity

JXG is a benign lesion of unknown incidence. It is the most frequent type of non-langerhans histiocytosis with a median age of 2 years. It usually presents as isolated cutaneous lesions. Multiple lesions, especially over the head and neck, may occur. The skin lesions tend to regress slowly with time. Extra-cutaneous and visceral involvements have been observed, the most common site being the eye. When the lesions are numerous, they may persist, hence the need for treatment with corticosteroids or chemotherapy. Histologically, the lesion consists of histiocytes admixed with an inflammatory infiltrate of variable density. The lesions are initially monomorphic and very cellular, progressively enriched with multinucleated giant cells of Touton and foamy cells, followed by spindle cells. We report an 8-year old girl with JXG of early type without multinucleated and foamy cells. This case presented as a tumour in the inferior meatus of nasal cavity, clinically simulating a rhabdomyosarcoma. This atypical clinical and histological presentation with benign evolution should be recognized since it requires only local treatment.     

Juvenile dermatomyositis. Clinical and epidemiologic experience

27 cases with a diagnosis of Juvenile Dermatomyositis were studied from a total of 1307 patients who suffered from connective tissue diseases; 19 of which met the diagnosis criteria of Bohan and Peters. Females were the most frequently affected. 52.63% of the cases presented the first symptoms between 5 and 9 years of age. Skin lesions, debility in inferior extremities and fever were the most frequent motives of consultation. The Aldolase and LDH were the muscular enzymes whose values increased in the majority of the cases. The electromyography was more sensible than the muscular biopsy in the diagnosis of the disease. We suggest that the epidemiologic and clinical characteristics found in our study should be taken into account for further accurate diagnosis of Juvenile Dermatomyositis in Venezuela.     

Juvenile xanthogranuloma developing after treatment of Langerhans cell histiocytosis: case report and literature review

The synchronous or metachronous development of Langerhans cell histiocytosis and non-Langerhans cell histiocytosis in the same patient is rare. To date, only seven cases of xanthogranulomas developing in young patients with a history of Langerhans cell histiocytosis and systemic therapy have been reported in the literature. As of yet, the pathogenesis and the clinical significance of this phenomenon are unclear. We report the case of a 3 year old boy who developed juvenile Xanthogranulomas on the forehead and right upper eye lid 1.5 years after systemic therapy for monosystemic Langerhans cell histiocytosis of the bone and complete disease remission.     

Tumor induction in host-versus-graft disease. I. Clinical and pathologic features.

Perinatal C57BL/1 mice given injections of (SJL/J X C57BL/1)F1 spleen cells developed a highly lethal runting syndrome, designated host-versus-graft disease (HVGD). The mortality was related to the dosage of F1 cells. Acute pathologic changes resembled those occurring in parent leads to F1 graft-versus-host disease (GVHD), except for more pronounced plasmacytosis. Mice suffering from HVGD recovered clinically with no sequelae except for a slight increase in the incidence of lymphomas over control mice. Such mice were hyperreactive to F1 cells utilized to initiate the original HVGD syndrome. Most of the tumors developed in those animals receiving the initial injection of F1 spleen cells within 24 hours of birth. Tumor incidence was unrelated to the clinical severity of HVGD. By contrast, GVHD in the same strain combination resulted in a much higher incidence of lymphomas in a much shorter time. Parental strain cells were detectable in the F1 hosts up to the time of tumor development. HVGD has a low tumor induction potential; GVHD has a high tumor induction potential.     

Juvenile papillomatosis (epitheliosis) of the breast. A clinical and pathologic study of 13 cases

The clinical and pathologic findings of 13 patients with juvenile papillomatosis (JP) (epitheliosis) of the breast are analyzed. The average age was 25 years, with a range from 15 to 42. Family history of breast carcinoma was observed in 33%. Carcinoma did not develop in any patient after the diagnosis of JP. A co-existing carcinoma was present in 15% of the patients. This study confirms that JP may be related to family history of breast carcinoma and that the patients themselves may be at increased risk for the development of cancer. A long-term follow-up for these patients and relatives is needed so that additional information and better knowledge of this entity can be obtained.     

Supravalvular aortic stenosis. Clinical and pathologic observations in six patients

Supravalvular aortic stenosis with a mean pressure gradient of 101 mm Hg was encountered in six patients aged 1 1/2 to 12 years. Three patients had Williams syndrome. In two other patients the stenosis was familial. The angiographic/anatomic subtype of deformity was hourglass in four patients, diffuse in one, and membranous in one. Four patients are alive following successful surgical repair; the other two died without surgery. Microscopically, disorganized medial elements with fibrotic intima sometimes containing lacunae were observed in five cases; the one other had valvelike tissue only. Ultrastructurally, thick irregular elastic fibers, abundant swirling collagen, hypertrophied smooth-muscle cells, and scant ground substance characterized the medial tissue defect. Although hemodynamics during intrauterine development may predispose to localization of the stenosis to the supra-aortic valvar region, the cause for the mural dysplasia remains uncertain.     

鲍文样丘疹病的临床与病理观察

目的：研究鲍文样丘疹病的原因、临床病理特征及鉴别诊断要点。方法：对１５例患者进行临床病理分析；１２例用ＰＣＲ方法检测ＨＰＶ、ＨＳＶ－Ⅱ、ＣＭＶ、ＣＴ、ＮＧ、ＵＵ等６种病原体及免疫组化ＰＣＮＡ检测；跟踪观察部分病人病情变化。结果：鲍文样丘疹病大体观有典型形态特征，镜下与鲍文病类似，可表现有棘细胞的轻￣重度不典型增生，该分裂象易见。６种病原体检查部分呈阳性，但未发现明确相关性。随访观察１￣７年，预后良     

Indeterminate cell histiocytosis. Clinical and pathologic study in a pediatric patient

Indeterminate cell histiocytosis is a rare disorder involving altered homing mechanisms of the cutaneous histiocytic/dendritic system. It has been described predominantly in adults, with less than a dozen cases in children. A 13-year-old adolescent girl presented with a 4-year history of asymptomatic erythematous nodules and plaques, measuring from 1 to 5 cm in diameter, that were located mainly on the trunk and proximal portions of her limbs. A skin biopsy showed dermal diffuse infiltration of histiocytic cells. Most of the histiocytic cells were strongly positive for S100 protein. No Birbeck granules were found. Treatment with topical steroid was ineffective. After 6 months of pure coal tar and 5% 5-fluorouracil cream, an almost total clearing of lesions was observed. An accurate diagnosis of this condition is mandatory in order to avoid unnecessary treatments. Conservative management is also discussed.     

Juvenile and adult xanthogranuloma: A 30-year single-center experience and review of the disorder and its relationship to other histiocytoses

BackgroundJuvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis whose cell of origin, etiology and pathogenesis are not fully understood. We aimed to provide an update on histopathologic and immunophenotypic profile of this well-characterized entity whose relationship to the other histiocytoses has received renewed attention in light of recent molecular genetic studies.Materials and methodsA retrospective review of all the cases with the pathologic diagnosis of “xanthogranuloma” was performed on our archives from 1989 to 2019.ResultsA total of 525 patients with 547 lesions diagnosed as JXG were identified with the median age of 4.5 years, a male predominance (M:F ratio 1.3:1) and a predilection for the head and neck region (40.8%). Cutaneous lesions comprised 76.8% cases and another 15.7% presented within soft tissues. The most common non-soft tissue, extracutaneous lesions included the brain (2.6%), and lungs (1.8%). Three basic histopathologic patterns were identified: early classic (EJXG) (14.2%), classic (CJXG) (45.3%), and transitional JXG (TJXG) (40.5%). Multinucleated giant cells, either Touton or non-Touton, were most frequently present in CJXG followed by TJXG. Mitosis was rare (<1/10 high-power field) among different patterns. There was an association among the patterns and lymphocytic infiltrates (P = 0.036), and presence of Touton or non-Touton giant cells (P < 0.001 for both) but not for mitotic count (P = 0.105) or eosinophilic infiltrates (P = 0.465). Additionally, there was a correlation between age groups and presence of non-Touton giant cells (P = 0.012) but not for Touton cells (P = 0.127). We have demonstrated that immunophenotypic expression of the lesion was not associated with age at diagnosis nor morphologic pattern: factor XIIIa 192/204 (94.1%), CD11c 75/77 (97.4%), CD4 82/84 (97.6%), CD68 200/201 (99.5%), CD163 15/15 (100%), CD1a 1/110 (0.9%), S-100 48/152 (31.6%), CD31 15/21 (71.4%), and vimentin 104/105 (99.0%).ConclusionWe have documented in a substantial series of cases of JXG that there is a correlation between one of the three basic histopathologic patterns with age at diagnosis, but with a consistent immunophenotype among the three patterns. Considering sensitivity and specificity rates, we suggest that a combination of CD11c, CD4, CD1a and either CD163 (preferred) or CD68 stains provides more specific diagnostic yield in the differentiation of JXG from other histiocytic disorders. JXG is also discussed in terms of its relationship and distinction from other similar histiocytic disorders in the context of MAPK/ERK pathway mutations.     

Clinical syndromes with variable pathologic features

Frequently, placentas sent for pathologic examination include a clinical diagnosis that does not suggest a specific placental lesion. Pathologists who do not have great experience in this field may need some assistance with selecting the pertinent placental lesions to look for. This brief outline is included to define these conditions and present a list of the specific placental lesions that deserve consideration. The placental examination should be directed with the goal of identifying or noting and recording specifically the presence or absence of the relevant pathologic lesions. The syndromes or conditions considered in this context include neonatal encephalopathy, preterm birth, fetal growth restriction, maternal diabetes mellitus, thrombophilias, HELLP syndrome, and fetal hydrops.     

Acute simian varicella infection. Clinical, laboratory, pathologic, and virologic features.

Five African green monkeys inoculated intratracheally with 7.5 x 10(3) to 1.4 x 10(5) plaque-forming units of simian varicella virus (SVV) were subjected to clinical, laboratory, pathologic, and virologic analyses to study the pathogenesis of acute varicella. All animals developed viremia and rash and were sacrificed 8 to 11 days post-infection. No serum was available for postmortem serologic studies. Examination of multiple organs for pathologic changes and for SVV-specific antigen and nucleic acid revealed inflammation, hemorrhagic necrosis, and intranuclear Cowdry A inclusions in liver, lung, lymph node, and spleen; mild inflammation without necrosis in adrenal gland, kidney, and bone marrow, and SVV-specific antigen and nucleic acids in all viscera examined. No pathologic changes, SVV antigen or nucleic acids were detected in the spinal cord or in the brain from any of the monkeys. Ganglia revealed mild inflammation but no necrosis, and intranuclear inclusion bodies in non-neuronal cells of one trigeminal ganglion; SVV antigen and nucleic acids were detected in both non-neuronal and neuronal cells in ganglia. The pathologic and virologic findings in viscera are consistent with those described in viscera of humans with disseminated zoster, but the mild inflammatory changes in ganglia during acute simian varicella infection contrast with the extensive hemorrhagic necrosis and intranuclear inclusion bodies seen in human ganglia after disseminated varicella or zoster. Nevertheless, these studies show that ganglia become infected with varicella virus during primary infection, although the route of primary ganglionic infection remains to be determined, and indicate the possible usefulness of the SVV model to study varicella pathogenesis in humans.     

Clinical and pathologic study of two siblings with arrhythmogenic right ventricular cardiomyopathy.

ARVC is a cardiomyopathy in which the right ventricular myocardium is replaced by fibroadipose tissue. Males are affected slightly more often than females and, in those cases which are familial, the pattern of inheritance is usually autosomal dominant with incomplete penetrance. We examined the hearts of two sisters, ages 17 and 14, with no family history of heart disease. The older sibling, who was previously considered healthy, died suddenly, while the younger sibling developed congestive heart failure and received a cardiac transplant. An autopsy of the older sibling and examination of the younger sibling's excised heart revealed severe examples of ARVC with minor differences. A thick cap of fibroadipose tissue covered most, if not all, of each right ventricle and was transmural in some areas. Microscopically, lelt ventricles contained extensive myocyte disarray and multifocal fibrosis. The coronary arteries displayed intimal hyperplasia with disruption of the internal elastic lamina, similar to fibromuscular dysplasia. These two cases comprise a unique familial grouping in a polymorphic disease. Despite the male predominance and autosomal dominant inheritance in ARVC, the only members affected in this family were female, and an autosomal dominant pattern of inheritance, even with incomplete penetrance, would be unusual. In addition, we identified changes in the coronary arteries similar to fibromuscular dysplasia and corroborated recently reported changes in the left ventricle of patients with ARVC, providing evidence that this disease, in its most severe form, involves the entire heart.     

Clinical and pathologic aspects of recurrent placental villitis

In a retrospective survey, recurrent villitis was identified in ten of 59 patients in whom placental villitis had been diagnosed. The ten patients had a total of 41 pregnancies, with a reproductive loss of 60 per cent. In addition to enhanced fetal losses in all trimesters of gestation and postnatally, the incidences of fetal growth retardation and premature delivery were increased. There was no evidence of recent TORCH (toxoplasma, rubella, cytomegalovirus, herpes) infection, but all patients tested had rubella immunity. In six patients genital cultures were positive for gonorrhea and assorted microorganisms. Uterine abnormalities, including two septate uteri, one incompetent cervix, one submucosal leiomyoma, and one retroflexion, were common, and vaginal bleeding had occurred in five patients. Other factors included obesity (five patients) and clinical and laboratory evidence of autoimmunity (four of the five patients tested). In a control group of 20 patients with nonrecurrent villitis, the perinatal loss rate (37 per cent) was lower, and the incidences of positive cultures, uterine structural anomalies, obesity, and autoimmunity were also lower. Placental histologic findings included decidual plasma cell and intervillous fibrin and histiocytic infiltration, in addition to villous inflammation. These lesions, although consistent for a given patient, defined two clinically relevant groups of patients. The results of this study suggest that recurrent villitis is more frequent than previously reported, that it is associated with high perinatal mortality, and that immunologic and structural abnormalities in the host may play a role in its pathogenesis.