Cutaneous Langerhans Cell Histiocytosis Research Articles

Congenital localized cutaneous Langerhans cell histiocytosis in a Holstein calf.

Distinct solitary dermal nodules, either covered by an alopecic, or sometimes ulcerated, epidermis, were noticed on the head of a stillborn Holstein calf. The head was submitted for autopsy, and the nodules were found to consist of homogeneous, diffuse pale-yellow, soft-tissue masses with distinct margins that elevated the epidermis above the adjacent skin. Histologically, the dermal nodules were well-delineated on the deep margin approaching the cutaneous muscle and consisted of perivascular neoplastic infiltrates of round cells that in some places coalesced into sheets that extended into the dermis and subcutis. Neoplastic cells separated adnexa and collagen. Immunohistochemistry revealed intense tumor cell expression of vimentin, Iba1, E-cadherin, and CD204; expression of CD18 was faint. The masses were diagnosed as Langerhans cell histiocytosis. Congenital cutaneous Langerhans cell histiocytosis has not been reported previously in cattle, to our knowledge, and should be included in the differential diagnosis of congenital nodular skin lesions.

Metastatic Cutaneous Langerhans Cell Histiocytosis in a Flat-Coated Retriever Treated with Doxorubicin and Prednisone.

A 2 yr old female intact flat-coated retriever dog was presented for evaluation of a histologically diagnosed cutaneous Langerhans cell histiocytosis of the muzzle with right mandibular nodal metastasis and suspected prescapular lymph node metastasis. Chemotherapy (lomustine 60 mg/m2 by mouth as a single dose) and glucocorticoid therapy (prednisone ∼20 mg/m2 by mouth every 24 hr) were initiated. Progressive disease occurred 21 days after lomustine administration. Doxorubicin (at 30 mg/m2 IV every 3 wk) was administered as a second-line therapy. Prednisone was continued at the same dose. Partial response was noted 1 wk after initiation of doxorubicin and sustained through doxorubicin #2. Complete remission was achieved following doxorubicin #3 (63 days from the start of doxorubicin rescue therapy). Progressive disease was noted after doxorubicin #5, for a total duration of response to doxorubicin of 105 days. Further rescue treatment with vinorelbine at 15 mg/m2 IV was elected. Progressive disease and clinical decline were noted 1 wk after initiation of vinorelbine. The patient was euthanized because of clinical decline 126 days after histopathologic diagnosis and 114 days after chemotherapy treatment was initiated.

Histiocytic Diseases.

Canine cutaneous histiocytomas originate from Langerhans cells. Multiple histiocytomas are referred to as cutaneous Langerhans cell histiocytosis. Feline pulmonary Langerhans cell histiocytosis causes respiratory failure owing to extensive lung infiltration. Localized and disseminated histiocytic sarcomas usually arise from interstitial dendritic cells. Primary sites include spleen, lung, skin, brain (meninges), lymph node, bone marrow, and synovial tissues of limbs. An initially indolent form of localized histiocytic sarcomas, progressive histiocytosis, originates in the skin of cats. Hemophagocytic histiocytic sarcomas originates in splenic red pulp macrophages. Canine reactive histiocytoses (systemic histiocytosis and cutaneous histiocytosis) are complex inflammatory diseases with underlying immune dysregulation.

Application of 18F-FDG PET/CT in Langerhans Cell Histiocytosis.

Purpose This study aims to explore the application value of the 18F-FDG PET/CT imaging in diagnosing, staging, and typing Langerhans cell histiocytosis (LCH) via the morphological and metabolic analyses of the 18F-FDG PET/CT images. Methods We retrospectively analyzed the 18F-FDG PET/CT images and clinical data of nineteen patients with LCH. The shape, size, density, distribution, and 18F-FDG uptake of all lesions were documented. In addition, the SUVmax of the lesions, liver, and blood pool was measured prior to calculating the lesion-to-liver and lesion-to-blood pool ratios. Results Among the 19 analyzed patients, the positive rate of the PET/CT image was 94.7% (18/19), with 1 false negative (5.3%, 1/19) case occurring in the cutaneous LCH. Among the 76 lesions, 69 were FDG-avid lesions (69/76, 90.8%). Additionally, we observed no FDG uptake in 7 lesions (7/76, 9.2%). In contrast, 59 lesions (59/76, 77.6%) were abnormal on diagnostic CT scan, but 17 lesions (17/76, 22.4%) were undetected. The 18F-FDG PET/CT image revealed additional 6 lesions in the bone, 4 in the lymph node, 3 in the spleen, and 3 occult lesions, which CT scan did not detect. Additionally, there were 6 cases with single-system LCH. The remaining 13 cases were multisystem LCH. Our 18F-FDG PET/CT image analyses altered the typing of 4 LCH patients. In the case of all lesions, the mean SUVmax of the 18F-FDG-avid lesions was 5.4 ± 5.1 (range, 0.8∼26.2), and the mean lesion-to-liver SUVmax ratio was 3.1 ± 2.52 (range, 0.7∼11.9), and the mean lesion-to-blood pool SUVmax ratio was 4.6 ± 3.4 (range 0.7∼17.5). Conclusion The 18F-FDG PET/CT image plays an essential role in LCH diagnosis, primary staging, and typing. It can accurately evaluate the distribution, range, and metabolic information of LCH, providing a vital imaging basis for the clinical evaluation of disease conditions, selection of treatment schemes, and determining patient prognosis.

CPC14: A rare adult presentation of cutaneous Langerhans cell histiocytosis associated with acute transformation of myeloid leukaemia

CPC14: A rare adult presentation of cutaneous Langerhans cell histiocytosis associated with acute transformation of myeloid leukaemia

Isolated cutaneous Langerhans cell histiocytosis in circumcised preputial skin

Isolated cutaneous Langerhans cell histiocytosis in circumcised preputial skin

Case Report: Characterizing the Role of the STXBP2-R190C Monoallelic Mutation Found in a Patient With Hemophagocytic Syndrome and Langerhans Cell Histiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disorder. HLH can be considered as a threshold disease depending on the trigger and the residual NK-cell cytotoxicity. In this study, we analyzed the molecular and functional impact of a novel monoallelic mutation found in a patient with two episodes of HLH. A 9-month-old child was diagnosed at 2 months of age with cutaneous Langerhans cell histiocytosis (LCH). After successful treatment, the patient developed an HLH episode. At 16 month of age, the patient went through an HSCT losing the engraftment 5 months later concomitant with an HLH relapse. The genetic study revealed a monoallelic mutation in the STXBP2 gene (.pArg190Cys). We transfected COS7 cells to analyze the STXBP2-R190C expression and to test the interaction with STX11. We used the RBL-2H3 cell line expressing STXBP2-WT-EGFP or R190C-EGFP for degranulation assays. Mutation STXBP2-R190C did not affect protein expression or interaction with syntaxin-11. However, we have demonstrated that STXBP2-R190C mutation diminishes degranulation in the RBL-2H3 cell line compared with the RBL-2H3 cell line transfected with STXBP2-WT or nontransfected. These results suggest that STXBP2-R190C mutation acts as a modifier of the degranulation process producing a decrease in degranulation. Therefore, under homeostatic conditions, the presence of one copy of STXBP2-R190 could generate sufficient degranulation capacity. However, it is likely that early in life when adaptive immune system functions are not sufficiently developed, an infection may not be resolved with this genetic background, leading to a hyperinflammation syndrome and eventually develop HLH. This analysis highlights the need for functional testing of new mutations to validate their role in genetic susceptibility and to establish the best possible treatment for these patients.

Adult-onset perianal Langerhans cell histiocytosis presenting as pruritus ani: a case report and review of the literature

BackgroundLangerhans cells belong to the histiocytic system and give rise to two tumors: Langerhans cell histiocytosis and Langerhans cell sarcoma. Clinical aggressiveness and degree of atypia distinguish the two neoplasms. Langerhans cell histiocytosis can infiltrate a single or multiple organ systems and particularly affects bone, skin, and lymph nodes. Perianal cutaneous Langerhans cell histiocytosis is a rare condition in adults, with 15 cases reported in the literature.CaseWe present the case of a 50-year-old hispanic man who presented with a 9-month history of pruritus ani and a personal history of diabetes insipidus. Punch biopsy confirmed a lesion of Langerhans cells origin but could not exclude Langerhans cell sarcoma because of limited sample size. An additional biopsy was planned as well as a positron emission tomography scan to determine the extent of disease spread. While the patient failed to follow up for repeat biopsy, the positron emission tomography scan was performed and was negative for metastatic disease. A stable perianal lesion of Langerhans cell histiocytosis with benign clinical features in a 50-year-old male despite lack of treatment is extremely rare and has not been described in the literature so far. Here, we review the presentation and workup of patients with Langerhans cell histiocytosis, review the relevant literature, and discuss treatment planning.ConclusionPerianal Langerhans cell histiocytosis is rare, and there should be a high index of suspicion with chronic or new perianal lesions, especially in a patient with a history of diabetes insipidus. It is also important to consider the patient’s full clinical course when it is not possible to reach a definitive pathological diagnosis before management.

Cutaneous Langerhans cell histiocytosis in adults: A retrospective cohort study of adult patients presenting to a single academic cancer center between 2003 and 2017

To the Editor: Due to the rarity of adult-onset Langerhans cell histiocytosis (LCH), guidelines on surveillance, staging, and management of cutaneous LCH are lacking.1 We determined the incidence and time to development of systemic LCH for patients first presenting to dermatology with cutaneous involvement of LCH and skin-limited symptoms and evaluated clinical features, disease course, and management.

真皮に Langerhans 細胞のび慢性浸潤がみられた 1 例 : 皮膚型 Langerhans 細胞組織球症の初期病変か

真皮に Langerhans 細胞のび慢性浸潤がみられた 1 例 : 皮膚型 Langerhans 細胞組織球症の初期病変か

Case series of cutaneous Langerhans cell histiocytosis in Indonesian children; The clinicopathological spectrum.

Langerhans Cell Histiocytosis (LCH) is a rare disease characterized by the clonal proliferation of Langerhans cells, which are immunoreactive to S-100 and CD-1a/ CD207 (Langerin). Cutaneous involvement is the most common presentation of LCH in children. It is suggested that the patients with single-system LCH limited to the skin have a better prognosis than those with systemic involvement. Three histologic reactions of cutaneous LCH have been reported and are associated with the clinical types of LCH. These histological reactions include: proliferative, granulomatous, and xanthomatous. This study presents the clinicopathological features of ten cutaneous LCH cases collected from Dr. Sardjito General Hospital Yogyakarta Indonesia between 2014-2018. The ten cases showed various clinical features, in which some features mimic other diseases. The microscopic features of skin biopsies showed granulomatous reaction in 80% of cases and proliferative reaction in the other 20%. Five patients (50% of cases) who died had systemic manifestation of thrombocytopenia, anemia, icterus, hepatosplenomegaly, and revealed the granulomatous type from their skin biopsy specimens. The clinical recognition of LCH and subsequent histological reaction determination are important since some cases may develop multisystem disease and have a poor prognosis.

Langerhans cell histiocytosis in children: A retrospective case series of 126 cases.

Langerhans cell histiocytosis (LCH), a rare neoplasm of hematopoietic myeloid precursor cells, is clinically characterized by spontaneously resolving lesions to a progressive life-threatening multisystem disorder. Diagnosing LCH in children is challenging as it mimics other skin disorders. This study describes the varied clinical presentation and disease course in children less than 18years diagnosed with LCH. We performed a retrospective observational study of all cases diagnosed with LCH presenting to a children's hospital in the last 26years. Data on history, cutaneous and systemic examination, and laboratory evaluation performed, were recorded. A total of 126 children diagnosed with LCH were included in the study. There were 68% cases limited only to skin, and 32% children with multisystem involvement at the initial presentation. Scaly papules were the most common morphologic finding in skin. The skeletal system was the second most common organ system to be affected. Failure to thrive was a common symptom. Progression of skin to systemic involvement was seen in 27.9%. In 76.7%, skin lesions cleared over a period of 2 to 4years. Complete remission was seen in 56.9% of children over a period of 3 to 7years, while 8.1% children died of complicationsand 31.8% were lost to follow-up. Long-term follow-up in this study has shown cutaneous LCH without systemic involvement has a good prognosis. Skin involvement,along with failure to thrive, was the most common clinical presentation in our study. The skeletal system was the second most common organ system involved.

Isolated Cutaneous Langerhans Cell Histiocytosis Presenting in an Adult Male

Langerhans cell histiocytosis (LCH) is an infrequent clonal proliferative disorder of myeloid dendritic cells. It has a wide variety of cutaneous manifestations and retains the possibility of systemic implications. Because LCH is predominantly a disease of childhood, there are well-established clinical definitions, as well as guidelines regarding workup and treatment, in the context of pediatric disease. Here we present a case of isolated cutaneous LCH in an adult male, followed by a discussion of our diagnostic plan and treatment course. The patient exhibited a small, excoriated, yellow papule on his inferior forehead during a skin examination. The specimen underwent tangential shave biopsy; histopathologic evaluation with appropriate immunohistochemical staining confirmed a diagnosis of cutaneous LCH. After thorough investigation via serologic and imaging diagnostics, we confirmed isolated cutaneous disease. The patient underwent wide local excision (WLE) with no evidence of recurrence. It is crucial to appropriately screen all patients diagnosed with cutaneous LCH for internal organ involvement. The authors aim to highlight the need for further investigations to ultimately dictate standardized management and treatment for isolated cutaneous LCH in the adult population.

444 Cutaneous langerhans cell histiocytosis in adults: Clinical features, disease course, and management among patients treated at the Dana-Farber Cancer Institute between 2003-2017

Langerhans Cell Histiocytosis (LCH) is a rare inflammatory neoplasm originating from myeloid dendritic cells1. Empiric treatment for LCH in adults has been described as a “roulette wheel” as there lack guidelines on staging, surveillance, and management1. Patients with cutaneous LCH may develop systemic disease and secondary hematologic malignancies; however, incidence and time to progression remains to be studied2. This is a retrospective cohort study of 31 patients (median age 53) with cutaneous LCH at the Dana-Farber Cancer Institute between 2003 to 2017 and literature review. 20 (64.5%) had cutaneous only disease. 5 (16.1%) had cutaneous LCH and developed extra-cutaneous LCH, with average time to progression of 84.2 months (range 46-131). 3 (9.7%) had extra-cutaneous LCH and then developed cutaneous LCH, with average time to onset of 45.7 months (8-84). 3 (9.7%) presented with cutaneous and extra-cutaneous LCH. 8 (26%) developed a secondary malignancy including diffuse large B cell lymphoma (n=2), breast cancer (n=1), chronic myelomonocytic leukemia (n=1), cutaneous T-cell lymphoma (n=1), melanoma (n=1), and thyroid cancer (n=2), with average time to diagnosis of 102 months (45-262). Patients were treated with a variety of skin-directed and/or systemic therapies. Literature review of cutaneous LCH in adults revealed 47 papers with 60 total cases. Our tertiary center experience represents the largest known retrospective cohort of cutaneous LCH in adults and may guide staging, surveillance, and treatment. 1. Allen CE et al. Langerhans-Cell Histiocytosis. N Engl J Med. 2018; 2. Edelbroek JR et al. Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy. Br J Dermatol. 2012.

CyclinD1 Is Useful to Differentiate Langerhans Cell Histiocytosis From Reactive Langerhans Cells.

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by clonal proliferation of neoplastic Langerhans cells (LCs). LC proliferation can also be seen in different reactive dermatosis. CyclinD1 is a downstream marker of mitogen-activated protein (MAP) kinase pathway, which is often activated in LCH. This study aimed to evaluate the role of cyclinD1 to differentiate reactive LC proliferation from LCH. All cases of cutaneous LCH diagnosed by biopsy in the past 3 years (n = 13) were immunostained with CD1a, p53, CD31, and cyclinD1. Seven cases each of discoid lupus erythematosus (DLE) and lichen planus (LP) were taken as control. Presence of p53, CD31, and cyclinD1-positive LCs (CD1a-positive) were compared in the dermis. In all LCH cases, dermal neoplastic LCs showed diffuse CD1a positivity and 12 cases (92.3%) showed variable (30%-70%) cyclinD1 expression. Weak p53 and CD31 expression were seen in 61.5% and 46.1% of LCH cases, respectively. In the control group, 5 cases of LP and 4 cases of DLE showed variable LC proliferation, highlighted by CD1a positivity. However, no case of reactive dermatosis showed cyclinD1 or p53 expression by the reactive LCs. Weak and patchy CD31 expression by the reactive LCs were found in 1 (25%) and 2 (40%) cases of DLE and LP, respectively. To conclude, cyclinD1 is frequently expressed in neoplastic LCs in LCH. It is an efficient marker to differentiate neoplastic from reactive LC proliferation, and can be used as a surrogate marker in LCH.

Langerhan's Cell Histiocytosis Masquerading as Intertrigo

Cutaneous Langerhan’s cell histiocytosis (LCH) is considered a great clinical mimicker and affects the scalp and intertriginous regions although it may be generalized. Cutaneous LCH is commonly misdiagnosed and thus patients can receive inadequate or inappropriate treatment for considerable periods of time. We present a case report of a patient who had LCH that was masquareding as intertrigo for years. With the proper diagnosis the patient had a remarkable response to methotrexate. This case highlights the importance of keeping Langerhan’s cell histiocytosis (LCH) on the differential and once the diagnosis is made, evaluating for extracutaneous LCH.

Cutaneous neonatal Langerhans cell histiocytosis: a systematic review of case reports

Background:Cutaneous langerhans cell histiocytosis (LCH) is a rare disorder characterized by proliferation of cells with phenotypical characteristics of Langerhans cells. Although some cases spontaneously resolve, no consistent variables have been identified that predict which cases will manifest with systemic disease later in childhood.Methods:A systematic review (Pubmed, Embase, Cochrane database and all published abstracts from 1946-2018) was undertaken to collate all reported cases of cutaneous LCH in the international literature. This study was registered with PROSPERO (CRD42016051952). Descriptive statistics and correlation analyses were undertaken. Bias was analyzed according to GRADE criteria.Results:A total of 83 articles encompassing 128 cases of cutaneous LCH were identified. Multiple lesions were weakly associated with an increased length of survival (R=0.304 (p<0.05)), Worse prognosis was associated with internal organ involvement with a statistically significant chi squared statistic (χ2=14.96, 2DF p<0.001) and an elevated odds ratio ((OR)= 12.30 95% CI=2.67-56.74). Vesicular lesions (OR=10.8 95% CI=2.83-41.26), but not ulceration (OR=0.53 95% CI 0.12-2.05) were associated with greater risk of mortality.Conclusions:Congenital and neonatal LCH most commonly presents as multiple lesions in multiple anatomical sites at birth. Significant differences, including the associations of mortality with lesion morphology and number were seen in this neonatal cohort compared to overall pediatric LCH. These findings require validation in a large prospective cohort.

Cutaneous Langerhans cell histiocytosis – an indication for dermatological pharmacotherapy with topical nitrogen mustard

Cutaneous Langerhans cell histiocytosis – an indication for dermatological pharmacotherapy with topical nitrogen mustard

Coexistence of cutaneous Langerhans cell histiocytosis and reticulohistiocytosis with initial presentation of skull lesions

Coexistence of cutaneous Langerhans cell histiocytosis and reticulohistiocytosis with initial presentation of skull lesions

Solitary form of congenital self-healing reticulohistiocytosis

Abstract Congenital self-healing reticulohistiocytosis (CSRH) is a rare form of cutaneous Langerhans cell histiocytosis (LCH) that is localized and usually spontaneously resolves without widespread organ involvement. CSRH usually presents cutaneously in many shapes (nodular, vesicular, and bullous) and colors (red, brown, blue, purple), however it rarely occurs as a solitary lesion. The incidence of CSRH is largely unknown due to spontaneous regression and lack of recognition. However, of the 4 LCH cases per million pediatric patients, roughly 20% of all CSRH cases are reported as solitary lesions. We report an unusual solitary cutaneous occurrence of CSRH that was present congenitally.