The epidemiological and clinical characteristics of Langerhans cell sarcoma in the United States: A population study based on SEER data from 2000 to 2019.

Langerhans cell sarcoma (LCS) is a rare aggressive malignancy with a poor prognosis. Our knowledge about this condition is limited and mainly based on case reports, making it challenging to understand its epidemiology, clinical features, and patient outcomes. We conducted a retrospective study of LCS patients diagnosed between 2000 and 2019 using the Surveillance, Epidemiology, and End Results (SEER) database. The data were stratified based on age, race, stage, clinical pattern, and treatment method. Our study found that 57 LCS cases were reported in SEER registries between 2000 and 2019. Among these cases, most patients (50.9%) were over 60 years old and White (71.9%) with almost equal males to females ratio. About 45.6% of cases were localized while 47.4% were at distant stages. Of the patients, 50.9% underwent surgery, 45.6% received chemotherapy, and only 21.1% received radiotherapy. The overall survival rate for patients diagnosed with LCS in the United States is generally low with a 1-year overall rate of 63.8%. Certain factors can negatively impact prognosis, such as advanced stages of the disease, secondary tumors, or more than 1 tumor per patient. LCS is a rare disease with poor survival rates. Future research should incorporate global data for further statistically significant results. Moreover, investigating the molecular, genetic, and pathophysiological backgrounds of these tumors is crucial for developing targeted management strategies and improving prognosis.

Complexity of diagnosing and treating langerhans cell sarcoma: A case report.

INTRODUCTION: Langerhans cell sarcoma (LCS) is a very rare malignant tumor of Langerhans cells that may metastasize to many organs. The diagnosis of this tumor is difficult and its prognosis is poor. AIM: To report the difficulty to diagnose LCS, and discuss therapeutic management of this rare entity. CASE PRESENTATION: We report a case of LCS in a 52-year-old man who presented with an axillar lymphadenopathy. The diagnosis of nodular sclerosis type Hodgkin's disease was established after histologic examination. The patient was treated with chemotherapy (ABVD regimen: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine) and radiotherapy with a partial response. However, disease recurrence was observed and histological analysis confirmed the diagnosis of Langerhans cell sarcoma. A revision of the initial histological examination concluded to the diagnosis of sarcoma from the beginning. We chose the ESHAP (Etoposide, Methylprednisolone, Aracytine, Cisplatin) regimen and clinical improvement of LCS was obtained after 2 cycles but the patient had a fatal outcome and died by disease progression. CONCLUSION: Because of its rarity, diagnosis is difficult and an optimal treatment strategy for this disease has not yet been identified. Polychemotherapy can be an effective modality for the treatment of LCS.

Left Forearm Langerhans Cell Sarcoma Demonstrated by 18 F-FDG PET/CT.

ABSTRACT: Langerhans cell sarcoma is a rare neoplastic proliferation of Langerhans cells with a poor prognosis. We report FDG PET/CT findings of Langerhans cell sarcoma in the left forearm of a 77-year-old woman who presented with progressive enlargement of the left forearm mass for over 2 months. 18 F-FDG PET/CT demonstrated a high FDG uptake by the mass along with several FDG-avid enlarged lymph nodes in the left arm and axilla. Pathology examination of the biopsied specimen from the left forearm mass led to a diagnosis of Langerhans cell sarcoma.

Langerhans cell sarcoma with BRAF-V600E mutation and hemophagocytosis: An autopsy report.

Langerhans cell sarcoma (LCS) is a rare high-grade neoplasm of langerhans cell phenotype having unambiguous malignant cytological features. We report such a rare case in a 20-year-old man who presented with dyspnea and high-grade fever. On evaluation, he had generalized lymphadenopathy, hepatosplenomegaly, and a large anterior mediastinal mass. Fine needle aspiration from the mediastinal mass and bone marrow aspirate showed numerous atypical cells, many of which showed grooved nuclei. In addition, the bone marrow showed prominent hemophagocytosis. The patient had a stormy hospital stay and succumbed to the illness. The autopsy revealed a rare multisystem involvement by LCS involving the lymph nodes, liver, spleen, lungs, and intestine, which harbored a BRAFV600E mutation and was associated with hemophagocytosis.

Unusual presentation of Langerhans cell sarcoma as bilateral submandibular gland swelling - A rare case report.

Langerhans cell sarcoma (LCS) is a rare malignant tumor of Langerhans cells and uncommonly involves head and neck regions. Unlike Langerhans cell histiocytosis (LCH), it has an aggressive clinical course with malignant cytological features. Till now, a handful of cases have been reported and the common anatomical sites involved are skin, lymph node, and bone in loco - regional cases and lymph node, lung, liver, spleen, and bone in disseminated disease. Due to its rarity, standard protocols of treatment for these patients are not yet well established. Herein, we report such a case in a 25-year-old male presenting with a bilateral submandibular swelling, which was diagnosed as LCH on Fine Needle Aspiration Cytology (FNAC) and later confirmed to be a case of LCS in histopathological examination and immunohistochemistry. The authors are aware of only a single similar case being reported in the English literature.

The Expression of Insulin-Like Growth Factor 2 Messenger RNA-Binding Protein 3 in Langerhans Cell Histiocytosis and Langerhans Cell Sarcoma.

Langerhans cell neoplasms, which include Langerhans cell histiocytosis and Langerhans cell sarcoma, are tumors that originate from dendritic cells. Langerhans cell sarcoma is defined as a high-grade neoplasm with overtly malignant cytological features and the Langerhans cell-like phenotype, and generally has a poorer prognosis and more aggressive phenotype than Langerhans cell histiocytosis. Insulin-like growth factor 2 messenger RNA-binding protein 3 (IGF2BP3 or IMP3) is an oncofetal protein that is expressed in various cancer types; its expression is often associated with a poor prognosis and aggressive phenotype. Here, we used immunohistochemistry to evaluate IGF2BP3 expression in Langerhans cell neoplasms. IGF2BP3 expression was scored as negative (< 1%) or positive (≥ 1%) by immunohistochemistry. All 4 patients with Langerhans cell sarcoma (100%) and 6 of 22 pediatric (age < 18 years) patients with Langerhans cell histiocytosis (27.3%) had positive results for IGF2BP3; however, 16 of 22 pediatric patients with Langerhans cell histiocytosis (72.7%) and all 15 adult (age ≥ 18 years) patients with Langerhans cell histiocytosis (100%) had a negative result. Among patients with Langerhans cell histiocytosis, IGF2BP3 expression was independent of sex, location, prognosis, and BRAF V600E staining results. Taken together, these results indicate that IGF2BP3 expression may be a helpful marker for distinguishing Langerhans cell sarcoma from Langerhans cell histiocytosis in adult patients.

From the archives of MD Anderson Cancer Center: A case of concurrent follicular lymphoma and Langerhans cell sarcoma with a review of the literature.

Transdifferentiation of follicular lymphoma to a Langerhans cell neoplasm is rarely reported and not well understood. Here we present a case, review the literature and discuss some of the biological underpinnings of lineage switch of B cells to histiocytes/Langerhans cells. A 31-year-old woman had follicular lymphoma (FL) and Langerhans cell sarcoma (LCS) co-localized above and below diaphragm. The FL was low-grade, had typical morphologic features, and was positive for CD10, BCL-2, and BCL-6. The LCS was cytologically atypical with necrosis and a high mitotic rate, and the immunophenotype supported Langerhans cell lineage positive for CD1a, CD207/langerin, and S-100 protein. Both tumors carried IGH-BCL2 and the LCS cells had immunophenotypic evidence of a residual B cell program, supporting the notion that these neoplasms are clonally related. The case reported is unusual because the patient was young and both diseases presented simultaneously, before any therapy. In addition, immunohistochemical analysis showed that the LCS was negative for BRAF V600E and phospho-ERK, suggesting that the LCS belongs to the known subset of Langerhans cell tumors lacking BRAF V600E and MAP2K1 mutations. Concurrent occurrence of FL and Langerhans cell neoplasm is an unusual phenomenon, with 10 cases reported previously: 4 Langerhans cell histiocytosis and 6 Langerhans cell sarcoma, including this case.

Langerhans cell sarcoma involving skin and showing epidermotropism: A comprehensive review.

Langerhans cell sarcoma (LCS) is rare and aggressive; patients have an overall survival rate of less than 50%. We present a 62-year-old man with a history of superficial spreading melanoma of the upper back with sentinel lymph node metastasis, Langerhans cell histiocytosis, and LCS. The patient presented with erythematous papules and scaly areas on his face, neck, arms, chest, abdomen, and legs. A skin biopsy revealed a proliferation of large neoplastic cells involving the dermis and with epidermotropism. These cells had atypical bean-shaped nuclei, with ample cytoplasm and abundant mitotic figures including atypical forms. Immunohistochemical studies showed the tumor to be diffusely positive for CD1a, S100 protein, and langerin (CD207) and negative for melanocytic markers. Some tumor cells were positive for cyclin D1. A diagnosis of LCS involving the skin was established. The present study is a very unusual case of LCS showing epidermotropism. The patient's history of metastatic melanoma posed additional challenges for diagnosis, underlying the need of immunophenotyping in these cases. Consensus for optimal standard therapy has not been established in LCS, and thus, early recognition is important since these neoplasms tend to recur and metastasize. LCS in skin is discussed and published cases are comprehensively reviewed.

Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression.

Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.

Concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma in a patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma.

The phenomenon of histiocytic/dendritic cell sarcomas arising through transformation of a pre-existed lymphoproliferative disease is called transdifferentiation. Langerhans cell sarcoma transdifferentiating from chronic lymphocytic leukemia/small lymphocytic lymphoma is extremely rare and all the reported cases were localized in lymph nodes. We present a case of concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, in which the chronic lymphocytic leukemia/small lymphocytic lymphoma preceded the development of the Langerhans cell sarcoma. A cutaneous lesion from a 63-year-old patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was biopsied. The histologic examination revealed a mixture of two cell populations infiltrating diffusely the dermis. The first was composed of small lymphoid cells with somewhat monotonous appearance and mild nuclear atypia positive for PAX5, CD79a, CD20, CD23, CD5, and LEF1. The second was composed of large cells with abundant cytoplasm and pleomorphic nuclei. These cells were positive for CD1a, CD207, and S100 protein and exhibited a high mitotic rate and a high MIB-1 immunostaining index. Therefore, two different entities, chronic lymphocytic leukemia/small lymphocytic lymphoma and Langerhans cell sarcoma, were detected in the same skin fragment. The patient died 3 years after initial diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.

A case of Langerhans cell sarcoma on the scalp: Whole-exome sequencing reveals a role of ultraviolet in the pathogenesis.

Langerhans cell sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway-related genes, CDKN2A and TP53 have been reported. Here we present a 70-year-old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD-L1, and the Ki-67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole-exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion of CDKN2A and TP53 mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD-L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS.

[Durable remission of Langerhans cell sarcoma attained by autologous hematopoietic stem cell transplantation following surgical resection].

Langerhans cell sarcoma (LCS) is a rare neoplastic proliferation of Langerhans cells with a poor prognosis. Owing to its rarity, standard treatment for LCS has not been established to date. Here, we report a case of LCS occurring in multiple lymph nodes in the right cervix in which remission is maintained by autologous hematopoietic stem cell transplantation (auto-HSCT) after surgical resection. A 58-year-old male presented with enlarged right submandibular lymph nodes. Positron-emission tomography/computed tomography (PET/CT) revealed multiple lymphadenopathies in his right cervix. We performed a lymph node biopsy, and he was diagnosed with LCS. We selected the CHOP regimen as the first-line chemotherapy; however, rapid disease progression was observed soon after the first cycle of the therapy. The neck dissection was performed on day 16 of the CHOP therapy. As the residual tumor was suspected, we started the second-line chemotherapy with a combination of etoposide, cisplatin, ifosfamide, and gemcitabine; complete remission was confirmed by PET/CT. Subsequently, the patient was administered high-dose chemotherapy with auto-HSCT. After 2 years of auto-HSCT, complete remission has been maintained. Although there is no report of auto-HSCT for LCS, it could be an effective therapeutic tool for the disease.

Incidence, Clinical Features, and Outcomes of Langerhans Cell Sarcoma in the United States.

BACKGROUND: Limited knowledge exists on the incidence, treatment patterns, and long-term outcomes of Langerhans cell sarcoma (LCS) in the United States. PATIENTS AND METHODS: We performed a retrospective study of LCS patients diagnosed between 2001 and 2014 using the Surveillance, Epidemiology, and End Results (SEER) and National Cancer Data Base (NCDB) databases. Incidence was calculated from SEER, and treatment patterns and outcomes were calculated from NCDB. RESULTS: A total of 25 and 52 cases of LCS were reported to SEER and NCDB, respectively. The overall incidence of the disease was 0.2 per 10,000,000 and did not differ by race (P = .56) or sex (P = .33). The median age at diagnosis was 62 (range, 19-90) years. Of the 52 patients from NCDB, 20 (39%) received chemotherapy as first-line therapy, 24 (46%) received surgery, and 15 (29%) received radiotherapy. The 1-year overall survival (OS) rate was 62%, and the median OS was 19 months. After censoring the patients with bone marrow and reticuloendothelial system involvement, no significant difference in OS was noted between the patients who were managed with or without surgery (P = .75). Postsurgical radiation or chemotherapy were not associated with improvement in median OS (P = .25). Patients who were managed with radiotherapy had a better OS compared to those who received no radiotherapy (P = .03). CONCLUSION: This dual-national registry study shows that LCS is extremely rare and has a poor prognosis. Radiotherapy may offer a survival advantage to patients with locoregional disease without bone marrow and reticuloendothelial system involvement.