Congenital self-healing reticulohistiocytosis with BRAF V600E mutation in an infant.

Congenital self-healing reticulohistiocytosis (CSHR) is a rare disorder characterized by benign skin lesions with a tendency to self-heal. Multiple skin lesions are usually present in CSHR. It is very difficult to distinguish between CSHR and an invasive Langerhans cell histiocytosis. We present a case of a 5-month-old infant girl who had hypopigmented skin lesions distributed over her neck, thorax and torso. The skin lesions regressed spontaneously 2 months after the diagnosis of CSHR and the child has remained in complete remission without any sign of recurrence over a 2-year follow-up. BRAF V600E mutation was detected in lesional cells along with a low Ki-67 proliferative activity of about 6%. BRAF oncogene-induced senescence might contribute to a mechanism of self-regression in CSHR; however, the exact role of the somatic BRAF V600E mutation in CSHR remains to be determined.

Congenital Langerhans cell histiocytosis: a good prognosis disease?

Abstract: Langerhans cell histiocytosis is rare and more frequent in children. The skin is affected in 50% of the cases and is the only site in 10%. Its course varies from self-limited and localized forms to severe multisystemic forms. Congenital cases are usually exclusively cutaneous and self-limited, with spontaneous remission in months. This study presents a rare congenital case, initially restricted to the skin, with subsequent dissemination and fatal outcome. A male newborn presented congenital disseminated erythematous scaly lesions. The biopsy was conclusive for Langerhans cell histiocytosis. The patient evolved into the multisystemic form in weeks, when chemotherapy was started, according to the LCH-2009 protocol; however, the patient was refractory to treatment and died.

Congenital cutaneous histiocytosis in a piglet.

A 2-week-old crossbred male piglet with numerous congenital, variably sized macules, plaques, and papules distributed all over the body was submitted for necropsy. Significant gross and histological lesions were restricted to the skin. On light microscopic examination, these cutaneous lesions corresponded to dermal and/or subcutaneous masses composed of spindle-shaped to round cells that multifocally contained hemosiderin; epidermotropism was not observed. Immunohistochemically, the neoplastic cells were strongly positive for CD204; moderately positive for CD163, lysozyme, and vimentin; and negative for Mac 387, α-1-antitrypsin, S-100 protein and E-cadherin; frozen tissues were not available for CD1a and CD11c. Transmission electron microscopic examination of sections from formalin-fixed tissues did not reveal Birbeck's granules. The clinical, morphological, and immunohistochemical results were consistent with a congenital cutaneous histiocytosis of non-Langerhans cell origin. The condition most resembled juvenile xanthogranuloma in humans, a generally skin-limited non-Langerhans histiocytic disorder that can be congenital. Cutaneous and/or systemic histiocytic disorders are well characterized in dogs and have been described in cats, and a case with some similarities to ours has been reported in a neonatal piglet, but this is to our knowledge the first immunohistochemically supported report of histiocytosis in the pig and congenital histiocytosis in animals.

Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease): ten-year experience at Dallas Children's Medical Center.

The real incidence of congenital self-healing reticulohistiocytosis (CSHR) may be underreported because of its high rate of spontaneous resolution and lack of clinical recognition. Currently, there are no criteria other than clinical that can reliably distinguish CSHR from cutaneous involvement by disseminated Langerhans cell histiocytosis (LCH). In this study we investigate the role of E-cadherin, Ki-67, and phosphorylated histone H3 (PHH3) immunohistochemical stains in distinguishing CSHR from disseminated LCH. We found that no significant difference was seen in the histologic features and the expression of E-cadherin, Ki-67, and PHH3 between the two groups; thus supporting the theory that CSHR and LCH represent different ends of a spectrum of the same condition.

Congenital self-healing reticulohistiocytosis mimicking diffuse neonatal hemangiomatosis.

Congenital self-healing reticulohistiocytosis (CSRH), a rare benign variant of Langerhans cell histiocytosis (LCH), is characterized by (a). congenital skin lesions, (b). a healthy infant with no systemic involvement, (c). the histopathologic finding of a Langerhans cell infiltrate and (d). spontaneous involution within the first year of life without sequelae. We report a Taiwanese girl born with widespread hemangioma-like lesions. The diagnosis of LCH was confirmed by finding a diffuse dermal infiltrate of S-100-protein- and OKT6 (CD1a)-positive mononuclear cells and the presence of Birbeck granules in 10% of the mononuclear cells ultrastructurally. The diagnosis of CSRH was further established by rapid and complete involution of the lesions in 3 months. No recurrence was noted for 7 years. Our case illustrates that CSRH can mimic diffuse neonatal hemangiomatosis clinically; thus, it is important to include CSRH in the differential diagnosis of congenital or neonatal hemangiomatosis.

Congenital self-healing reticulohistiocytosis presenting with hemorrhagic bullae.

Congenital self-healing reticulohistiocytosis is a variant of Langerhans cell histiocytosis. It is present at birth or appears in the neonatal period and involutes spontaneously within 3 to 4 months. Although the skin eruptions in most cases consist of papulonodules, several patients with vesicular or bullous lesions have been reported. We describe a case of congenital self-healing reticulohistiocytosis presenting hemorrhagic bullae that mimicked hemangioma.

Congenital self-healing reticulohistiocytosis with eye involvement.

Congenital self-healing reticulohistiocytosis (CSHR) represents the benign end of the spectrum of Langerhans cell histiocytoses, with spontaneous resolution of lesions within the first year of life. However, involvement of organ systems other than the skin has been described occasionally and recurrence of disease at sites distant from the skin has been documented. We report a case of CSHR with eye involvement that spontaneously resolved concurrent with resolution of skin lesions. Because multiple organ systems can be involved and recurrences are possible, long-term follow-up of these patients is indicated.

Histiocytic disorders with spontaneous regression in infancy.

The histiocytic disorders are uncommon, have a wide spectrum, and are poorly understood. We describe seven cases developing in infancy, seen during a period of 9 years at Asan Medical Center, Seoul, Korea. Clinically the patients had multiple papules over the face, trunk, and extremities that developed at birth or during infancy. Histopathologic examinations revealed an infiltrate of many histiocytic cells in the upper dermis with or without epidermotropism. Four cases were classified as congenital self-healing reticulohistiocytosis in that the histiocytes were identified as Langerhans cells by positive immunohistochemical staining for S-100 protein, ultrastructural studies showing many Birbeck granules, and spontaneous regression of the lesions within 1-4 months. One infant with a solitary lesion on the forehead was diagnosed as solitary, congenital, indeterminate cell histiocytoma because the histiocytic cells were S-100 protein positive, but meticulous ultrastructural studies did not detect Birbeck granules. The lesion was removed by shave excision. Two cases were classified as generalized eruptive histiocytoma. The histiocytic cells were S-100 protein negative and ultrastructurally Birbeck granules were absent. In one patient, eyeball- or popcornlike lysosomal structures were seen. The lesions regressed completely.

Enterovirus-associated haemophagocytic syndrome in a neonate.

A 3-d-old neonate presented with fever, hepatosplenomegaly, coagulopathy, thrombopenia and anaemia. Secondary haemophagocytic lymphohistiocytosis was suspected, as persistent cytopenias were associated with hypofibrinogenaemia, haemophagocytosis in bone marrow and decreased NK cell. There was no positive family lymphohistiocytosis history or parental consanguinity. Bacterial investigation proved negative. The diagnosis of enterovirus maternofoetal infection was carried out. The infant's condition improved with symptomatic therapy from day 7. Follow up at 1 y was normal without relapse. This is the first report of a neonatal enteroviral infection that was responsible for excessive macrophage activation.

Solitary congenital self-healing reticulohistiocytosis.

Congenital self-healing reticulohistiocytosis (CSHR) was first described in 1973 by Hashimoto and Pritzker. Since then, both multiple and solitary forms have been described. We report a further case of solitary congenital self-healing reticulohistiocytosis. CSHR is a rare disorder which frequently presents a diagnostic dilemma in the newborn. Nodular forms of systemic Langerhans cell histiocytosis may present in a manner similar to CSHR. Because their differentiation on histopathological grounds is impossible, physical examination, laboratory investigations, and follow-up are necessary to ensure a lack of systemic involvement. Although previously thought to represent a rare variant of CSHR, solitary lesions of CSHR account for almost 25% of reported cases. A review of the literature relating to solitary CSHR, and a consideration of the differential diagnosis of a solitary congenital nodule, are also presented.

Congenital self-healing reticulohistiocytosis. Report of a case with 7-year follow-up and a review of the literature.

A case of congenital self-healing reticulohistiocytosis in an otherwise healthy newborn boy is presented. Histological, immunohistochemical, and ultrastructural findings are described and the nosologic position of this entity is discussed.

Congenital self-healing reticulohistiocytosis. A new entity in the differential diagnosis of neonatal papulovesicular eruptions.

A case of congenital self-healing reticulohistiocytosis is described. The case is different from those previously described because papulovesicles, rather than the papulonodules that are usually characteristic of this disease, predominated. All lesions regressed within 2 months of presentation, and at 2-year follow-up, the patient continues to develop normally without recurrence of the eruption or progression to internal organ involvement. Electron microscopic examination revealed numerous Langerhans' granules admixed with myelinlike laminated dense granules characteristic of this disease. The unique physical presentation in this case, as well as the criteria used to differentiate this disorder from the more malignant forms of histiocytosis and other childhood papulovesicular eruptions, is emphasized.