Pediatric Langerhans cell histiocytosis: the impact of mutational profile on clinical progression and late sequelae.

Langerhans cell histiocytosis (LCH) is a clonal histiocytic disorder with recurrent mutations of BRAF and MAP2K1, but data on the impact of genetic features on progression and long-term sequelae are sparse. Cases of pediatric LCH with long-term follow-up from our institution were analyzed for mutations in BRAFV600 and MAP2K1 exons 2 and 3 by immunostaining with mutation-specific VE1 antibody, as well as allele-specific PCR and sequencing, respectively. Clinical and follow-up data were obtained from our files and a questionnaire sent to all former patients. Sixteen of 37 (43%) evaluable cases showed BRAFV600E, one case a BRAFV600D and eleven (30%) a MAP2K1 mutation. Nine cases were unmutated for both genes. All cases with risk organ involvement showed either BRAFV600 or MAP2K1 mutation. Patients with BRAFV600 mutation excluding Hashimoto-Pritzker cases had a significantly higher risk for relapses (p = 0.02). Long-term sequelae were present in 19/46 (41%) patients (median follow-up 12.5 years, range 1.0 to 30.8) with a trend for higher rates in mutated cases (mutated = 9/17, 53% versus non-BRAFV600/MAP2K1 mutated = 2/7, 29%). In addition, 8/9 cases with skin involvement including all Hashimoto-Pritzker cases (n = 3) were positive for BRAFV600E. Infants below 2 years more frequently had BRAFV600 mutations (p = 0.013). Despite favorable prognosis, pediatric LCH shows a high frequency of relapses and long-term medical sequelae.

[Tumor of the mesosalpinx with unclear differentiation]. / Tumor der Mesosalpinx mit unklarer Differenzierung.

Female adnexal tumors of probable Wolffian origin (FATWO) are rare tumors, which are mostly localized in the broad ligament or the mesosalpinx. They show high intratumor and intertumor variability of histological patterns (e.g. solid, tubular, cribriform and cystic) with usually unremarkable cellular and nuclear morphology and a lower mitotic rate. In general, they behave in a benign fashion but there are rare cases with malignant transformation, so that careful examination and surveillance are necessary. Differential diagnoses include Sertoli-Leydig cell tumors, metastasized endometrioid carcinoma and the FATWO-like variant of the endometrioid carcinoma of the fallopian tubes. The FATWOs express pancytokeratin, CD10, vimentin, calretinin and inhibin A. Estrogen and progesterone receptors are expressed in a minority of cases, whereas epithelial membrane antigen (EMA) is not detectable.

[Erdheim-Chester disease and Rosai-Dorfman disease: Pathological, radiological and clinical features of adult non-Langerhans cell histiocytosis]. / Erdheim-Chester- und Rosai-Dorfman-Erkrankung : Klinisch-radiologisch-pathologische Diagnostik von Non-Langerhans-Zell-Histiozytosen des Erwachsenenalters.

Non-Langerhans cell histiocytoses (N-LCH) of adulthood are rare disorders with heterogeneous pathogenesis, morphology and clinical presentation. In this review two disorders are presented, which predominantly develop in extracutaneous sites in adults. Erdheim-Chester disease is a rare nonhereditary clonal disorder of lipid storing histiocytes most commonly presenting as osseous involvement of the long bones. Other organ manifestations include the central nervous system (CNS), the cardiovascular system, the retroperitoneum and kidneys and less commonly the skin and the lungs. Immunohistochemical staining reveals positivity for the macrophage markers CD163, CD68 and lysozyme but CD1a and langerin are negative, in contrast to Langerhans cell histiocytosis. Rosai-Dorfman disease is considered to be a reactive histiocytic proliferation occurring mainly in lymph nodes. Prominent sinuses filled with commonly multinucleated, S100-positive histiocytes with emperipolesis are a characteristic feature and develops particularly as extensive lymphadenopathy with massive sinus histiocytosis but can also occur extranodally. Painless bilateral cervical lymph node enlargement is the most common clinical presentation. This review summarizes the clinical, radiological and histopathological findings and discusses the recent molecular advances in these rare disorders.

Allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia and pulmonary mucormycosis.

Mucormycosis is a serious invasive fungal infection in immunocompromised patients. Patients undergoing treatment for hematologic malignancies are predominantly prone to the pulmonary manifestation of mucormycosis. Historically, allogeneic hematopoietic cell transplantation (HCT) in patients suffering from pulmonary mucormycosis (PM) was considered contraindicated owing to mortality rates up to 90%. We present 3 patients with acute myeloid leukemia and PM who were treated with radical surgical debridement combined with high-dose liposomal amphotericin B (LAB), and subsequently underwent successful allogeneic HCT. To date, all 3 patients are in complete remission and show no signs of mucormycosis. Allogeneic HCT in patients with PM seems feasible provided that the infectious focus is completely removed surgically and adequate antifungal pharmacotherapy, such as high-dose LAB or posaconazole, is established.