Perianal Langerhans cell histiocytosis relieved by surgical excision

Mittal, Tarun; Davis, Mark D.P.; Lundell, Ryan B.

doi:10.1111/j.1365-2133.2008.08934.x

Cited by 14 publications

(11 citation statements)

References 13 publications

(21 reference statements)

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“…Patients with LCH often have dermal disorders such as seborrheic dermatitis [ 7 ] concomitant to LCH lesions [ 82 ], preceding LCH lesions [ 83 - 85 ], or following LCH lesions [ 86 ]. Perianal lesions [ 87 , 88 ] or a lesion on the soles [ 89 ] were also reported. Stein et al [ 90 ] reported that children who present with LCH from birth to 4 weeks of age are not diagnosed with LCH until an average of 3.5 months of age because the eruptions are nonspecific in nature [ 91 ].…”

Section: Reviewmentioning

confidence: 99%

Interleukin-1 loop model for pathogenesis of Langerhans cell histiocytosis

Murakami

Matsushita

Iwasaki

et al. 2015

Cell Communication and Signaling

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We propose Langerhans cell histiocytosis (LCH) is an inflammatory process that is prolonged by mutations. We hypothesize that Merkel cell polyomavirus (MCPyV) infection triggers an interleukin-1 (IL-1) activation loop that underlies the pathogenesis of LCH. Langerhans cells (LCs) are antigen presenting cells in the skin. When LCs encounter exogenous antigens, they migrate from the epidermis into draining lymphoid tissues to initiate T-cell activity. It has been proposed that LC migration-related factors, including E-cadherin, matrix metalloproteinase, and Notch ligand induce LCH activity. We found that the tyrosine phosphatase SHP-1, which binds IL-1 receptor-associated kinase 1, is expressed at a significantly higher level in LCH affecting multiple organ systems (MS-LCH) than in LCH affecting a single organ system (SS-LCH). IL-1 stimulates T helper 17 cells and their signature cytokine IL-17 had been a matter of controversy. We detected higher levels of IL-17A receptor expression in MS-LCH than in SS-LCH and proposed an IL-17 endocrine model that could settle the controversy. IL-1 is the first cytokine secreted in response to sensitizers and promotes LC migration from sentinel tissues. Myeloid differentiation primary response 88 (MyD88), downstream of the IL-1 receptor, has functions in both RAS signaling and inflammation, leading to human cell transformation. In 2010, an activating mutation in the B-rapidly accelerated fibrosarcoma gene (BRAF) V600E was found in LCH. This BRAF mutation induces phosphorylation of the extracellular signal-regulated kinase (ERK) that may play an important role with MyD88 in LCH pathogenesis. However, phosphorylated ERK (pERK) is rapidly dephosphorylated by dual specificity phosphatase 6 (DUSP6), and limited proliferation is predicted in BRAF mutant cells. MyD88 binds pERK via its D-domain, thereby preventing pERK–DUSP6 interaction and maintaining ERK in an active, phosphorylated state. We detected MCPyV-DNA in the peripheral blood cells of two out of three patients with LCH in high-risk organs but not in those of patients with LCH in non–high-risk organs (0/12; P = .029). MCPyV infection can trigger precursor LCH cells with BRAF mutation to produce IL-1; the IL-1 loop is amplified in all LCH subclasses. Our model indicates both BRAF mutation and IL-1 loop regulation as potential therapeutic targets.

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Section: Reviewmentioning

confidence: 99%

Interleukin-1 loop model for pathogenesis of Langerhans cell histiocytosis

Murakami

Matsushita

Iwasaki

et al. 2015

Cell Communication and Signaling

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“… 13 , 15 , 22 Perianal affection was the only presentation of the disease without systemic involvement in two cases, which were similar to our case. 6 , 17 In contrast, besides the perianal involvement, bone, 8 , 10 - 22 liver, 19 and lung 9 , 18 , 19 were concomitantly affected by the disease.…”

Section: Discussionmentioning

confidence: 98%

Perianal Langerhans cell histiocytosis: a rare presentation in an adult male

Abdou

MaherTaie

2017

Autops. Case Rep.

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Langerhans cell histiocytosis (LCH) is a rare disease characterized by a proliferation of cells that show immunophenotypic and ultrastructural similarities with antigen-presenting Langerhans cells of mucosal sites and skin. LCH in adults is rare, and there are still many undiagnosed/misdiagnosed patients. We describe LCH involvement of the perianal region of a 33-year-old male with a previous history of diabetes insipidus. The differential diagnosis and all the reported cases of LCH of the perianal skin involvement since its description in 1984 till 2016 are discussed. LCH should be considered in the differential diagnosis of perianal ulceration, especially in young patients where topical drug treatment has failed. The history of previous central diabetes insipidus of unknown etiology demands imaging studies in order to rule out central involvement of the disease.

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“…However, mucocutaneous involvement of adult-onset LCH has been reported to occur more commonly with multi-system disease than with single-organ disease (5), whereas gastrointestinal involvement by LCH among children aged <2 years has been considered to be an indicator of widespread multi-systemic disease and poor prognosis in most cases (8). …”

Section: Discussionmentioning

confidence: 99%

“…Involvement of the gastrointestinal tract is very rare in LCH, especially in adults, along with only a few isolated case reports in the literature indicating the involvement of the perianal skin and rectum (5). Likewise, albeit reported to be more common in adults than children, involvement of the thyroid gland in LCH has been considered to be extremely rare, even in the setting of multifocal disease (6).…”

Section: Introductionmentioning

confidence: 99%

An unusual case of adult-onset multi-systemic Langerhans cell histiocytosis with perianal and incident thyroid involvement

Gül¹,

Sisman²,

Cander³

et al. 2017

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryLangerhans cell histiocytosis (LCH) is a rare sporadic disease characterized by histiocytic neoplastic infiltration of various organ systems and a wide spectrum of clinical manifestations, ranging from benign and self-limiting to lethal. Herein, we report a rare case of adult-onset multi-systemic LCH in a 36-year-old male patient with an initial perianal presentation and incidental finding of subsequent thyroid gland involvement in the follow-up period. The patient with a history of perianal LCH treated with surgical excision and local radiotherapy was referred to our Endocrinology Department upon detection of hypermetabolic nodular lesions in the left lateral lobe of thyroid gland on positron emission tomography–computed tomography (PET/CT) scan in the nineth month of follow-up. Current evaluation revealed euthyroid status, a hypoechoic solid lesion of 13 × 9 mm in size with irregular borders in the left thyroid lobe on thyroid USG and cytologic assessment of thyroid nodule. The patient was diagnosed with suspected, oncocytic lesion, Hashimoto thyroiditis or LCH. The patient underwent total thyroidectomy and pathological assessment confirmed the diagnosis of Langerhans cell histiocytosis. Assessments in the sixth month of postoperative follow-up revealed euthyroid status with no thyroid tissue remnants or pathological lymph node on thyroid USG. In view of the multifocal lesions indicating multi-system disease, a systemic chemotherapy protocol with combination of prednisone (PRED) and vinblastine (VBL) has been planned by the hematology department.Learning points:Langerhans cell histiocytosis (LCH) shows a wide clinical spectrum and prognosis that ranges from benign and self-limiting single-system disease (with single or multifocal lesions) to a potentially lethal multi-system disease with severe organ dysfunction and death in some cases.It has been stated that the diagnosis is often delayed in perianal LCH unless LCH is specifically considered in the etiology, despite the fact that mucosal involvement may precede systemic involvement.Our findings support the statement that most of patients with LCH were PET positive at the time of initial diagnosis, while also emphasize the inclusion of this imaging modality as a part of the diagnostic workflow as well as in the setting of treatment response evaluation among adult LCH patients.

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Perianal Langerhans cell histiocytosis relieved by surgical excision

Cited by 14 publications

References 13 publications

Interleukin-1 loop model for pathogenesis of Langerhans cell histiocytosis

Interleukin-1 loop model for pathogenesis of Langerhans cell histiocytosis

Perianal Langerhans cell histiocytosis: a rare presentation in an adult male

An unusual case of adult-onset multi-systemic Langerhans cell histiocytosis with perianal and incident thyroid involvement

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