Malignant Histiocytosis Comprises a Phenotypic Spectrum That Parallels the Lineage Differentiation of Monocytes, Macrophages, Dendritic Cells, and Langerhans Cells.

Malignant histiocytoses (MHs), or the 'M group' of the Histiocyte Society classification, are characterized by neoplastic histiocytes with large pleomorphic nuclei. MH encompasses the diagnoses of histiocytic sarcoma, interdigitating dendritic cell sarcoma, and Langerhans cell sarcoma. We aimed to define the phenotypic spectrum of MH and examine the genotypic features across this spectrum. Using immunohistochemistry, we arranged the 22 cases into 4 subtypes that correspond to the lines of differentiation from monocytic and dendritic cell precursors as follows: (1) macrophage (n = 5): CD68+, CD163+, CD14+, and Factor 13a+; (2) monocyte-macrophage (n = 5): CD68+, CD163+, CD14+, S100+, and OCT2+; (3) dendritic cell (n = 6): CD68+, CD11c+, S100+, lysozyme+, ZBTB46+, and CD1a/langerin < 5%; and (4) Langerhans cell (n = 6): CD68+, CD11c+, S100+, ZBTB46+, CD1a+, and langerin+. The phenotypic subtypes align with those seen in low-grade histiocytic neoplasms as follows: MH-macrophage type correlates with Erdheim-Chester disease phenotype; MH-monocyte-macrophage type with Rosai-Dorfman disease phenotype, and MH-Langerhans cell type with Langerhans cell histiocytosis. Activating mutations in MAPK-pathway genes were identified in 80% of MH cases; 29% had mutations in the PI3k-AKT-mTOR pathway and 59% had mutations in epigenetic modulating genes. Strong expression of cyclin D1 was present in all cases, whereas p-ERK and p-AKT were not uniformly expressed. Eight of 22 (36%) MH cases were proven to be clonally related to a prior B-cell lymphoma. Defining the phenotypic spectrum of MH provides a guide to diagnosis and allows further exploration into the potential biological and clinical significance.

A rare case of cutaneous interdigitating dendritic cell sarcoma.

Interdigitating dendritic cell sarcomas (IDCSs) are aggressive tumors of dendritic cells, often presenting with lymphadenopathy. Fewer than 10 cases of primary cutaneous IDCS have been reported. Histopathologically, IDCS presents as atypical spindle cells with irregular nuclei, and therefore can be difficult to distinguish from melanoma, follicular dendritic cell sarcoma, and Langerhans cell tumors by H&E examination alone. We report a unique case of a man with cutaneous IDCS that was initially misdiagnosed as melanoma. Having previously undergone an excision of a reported "melanoma" on the neck, he presented with a new growth on the cheek. Histopathologic findings revealed an atypical dermal lymphohistiocytic infiltrate around vessels and cells forming nests along the dermal-epidermal junction. Immunohistochemical stains were strongly positive for S100, fascin, and lysozyme; on the other hand, CD1a, langerin, CD21, CD23, and SOX10 were negative. These immunohistochemical findings were consistent with IDCS, and the patient's prior biopsy specimen was then revisited. Similar staining revealed that lesion also to be a cutaneous IDCS. Follow-up imaging with PET scan was negative for metastases, supporting the diagnosis of primary cutaneous IDCS. Our findings contribute to the limited literature on cutaneous IDCS and highlight a potential pitfall in its diagnosis because of overlapping histopathologic features with melanoma.

Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma.

BACKGROUND: Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim-Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies across the World Health Organization diagnostic categories are lacking. METHODS: Tumor samples from a total of 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs), underwent hybridization capture with analysis of up to 406 cancer-related genes. RESULTS: Among the entire cohort of 102 patients, CDKN2A mutations were most frequent across subtypes and made up 32% of cases, followed by TP53 mutations (22%). Mitogen-activated protein kinase (MAPK) pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCS (72% vs. 0%; p < .0001). In contrast, NF-κB pathway mutations were frequent in FDCSs but rare in M group histiocytoses (61% vs. 12%; p < .0001). Tumor mutational burden was significantly higher in M group histiocytoses as compared with FDCSs (median 4.0/Mb vs. 2.4/Mb; p = .012). We also describe a pediatric patient with recurrent secondary histiocytic sarcoma treated with targeted therapy and interrogated by molecular analysis to identify mechanisms of therapeutic resistance. CONCLUSION: A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies. Our findings highlight the potential value of molecular testing to enable precise tumor classification, identify candidate oncogenic drivers, and define personalized therapeutic options for patients with these aggressive tumors. IMPLICATIONS FOR PRACTICE: This study presents comprehensive genomic profiling results on 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs). MAPK pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCSs. In contrast, NF-κB pathway mutations were frequent in FDCSs but rare in M group histiocytosis. A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies.

New insights inside the interdigitating dendritic cell sarcoma-pooled analysis and review of literature.

Interdigitating dendritic cell sarcoma is a rare haematological neoplasm with high debatable management protocols. The data extracted from 127 case reports published between 1981 and 2018 were analysed. The median age at diagnosis was 58 years with a male to female ratio of 1.65:1. The median OS and PFS of IDCS were 12 and 6 months, respectively, with a disease-specific mortality rate of 36.4%. Two-thirds of patients had a localised disease, while 30% had a disseminated form with 1-year mortality rates of 21.1% and 78.9%, respectively. Twenty per cent of cases were associated with other malignancies. Histologically, the proliferation of large spindle-shaped cells with fascicular growth was described in 84.3% of cases. Based on Cox-regression model, surgical resection was the only treatment modality linked to survival improvement with no recorded survival benefits of radiotherapy and chemotherapy. The 1-year mortality rates in resected and non-resected disease were 17.8% and 63.2%, respectively (P < 0.0001).

[Clinicopathological characteristics and differential diagnosis of interdigitating dendritic cell sarcoma].

Objective: To analyze the clinicopathological features and differential diagnosis of interdigitating dendritic cell sarcoma (IDCS). Methods: The clinical pathological features of 7 IDCS were analyzed. Among them, the follow-up results of 6 cases were available. Results: Among the 7 IDCS patients, 4 cases were male and 3 were female. The age of the patients ranged from 26 to 69 years.Three cases were originated from lymph nodes and 4 cases were originated from skin, stomach, adrenal gland and mesentery, respectively. Microscopically, the tumor cells presented as fascicular and storiform proliferation and infiltrated by lymphocytes. The tumor cells were short-spindle or ovoid, with indistinct border of cytoplasm. The immunohistochemistry results showed that tumor cells were S-100, Vim, CD68 and CD163 positive, and AE1/AE3, EMA, CD117, CD34, Desmin, SMA, CD1α, CD21, CD23, CD35, HMB45, Melan-A, MelanPan and ALK negative.The BRAF mutation and clonal rearrangement of T and B cells were not detected. Among the follow-up period of 7 IDCS patients, 3 occurred disease progressions. Conclusions: IDCS is extremely rare with unique pathological features, and its lesion is not limited to the lymph node. The IDCS patients with extensive lesions may have worse prognose. The differential diagnosis of IDCS includes other histiocytic and dendritic cell neoplasms, malignant melanoma and soft tissue neoplasms.

Primary cutaneous interdigitating dendritic cell sarcoma is a morphologic and phenotypic simulator of poorly differentiated metastatic melanoma: A report of 2 cases and review of the literature.

Interdigitating dendritic cell sarcoma (IDS) is a rare form of hematologic malignancy associated with an aggressive clinical course. Only 4 prior cases have been described as originating in the skin. We encountered two male patients ages 47 and 61years of age who presented with solitary cutaneous neoplasms diagnosed as IDS. Histologic exam showed a coalescing nested and multinodular proliferation of large pleomorphic epithelioid cells. In one case an initial diagnosis of melanoma was rendered. A recurrence 8months later was then interpreted as a primary cutaneous IDS. This patient died of widespread metastatic disease within 2years from his initial surgery. The other patient has recently undergone wide excision and radiation without any recurrence or metastatic disease during this short follow up time period. Both patients had a tumor exhibiting the same phenotypic profile comprising leukocyte common antigen, SOX10, S100, CD68, and CD163 positivity. In reviewing the 4 other reported cases, there is a similar older male predominance (mean age of 58years) although women affected were significantly younger (mean age of 28years); there was a predilection for the proximal extremities and the face. Patients treated with excision only developed recurrent disease with one patient subsequently dying of metastatic disease. Primary cutaneous IDS is a highly aggressive hematologic malignancy that has many overlapping features with poorly differentiated epithelioid and spindle cell melanoma including SOX10 staining. An aggressive treatment protocol at the beginning could optimize patient survival.

[Disseminated interdigitating dendritic cell sarcoma]. / Sarcoma diseminado de células dendríticas interdigitantes.

A 70 year-old woman was admitted to our hospital with a 3-month history of abdominal pain, weight loss and night sweats. On physical examination, she presented with a 5 cm diameter abdominal mass extended from epigastrium to the left flank, and at least three bilateral supraclavicular adenopathies. A disseminated interdigitating dendritic cell sarcoma was diagnosed through a biopsy of the abdominal mass. After that, a CHOP regime (cyclophosphamide, doxorubicin, vincristine and prednisone) was iniciated. She died after completion of the first cycle of treatment, six months after diagnosis.

Evidence of BRAF V600E in indeterminate cell tumor and interdigitating dendritic cell sarcoma.

BRAF V600E mutations have been reported in several histiocytic and dendritic cell neoplasms. In this case series, we report BRAF V600E-positive histiocytic and dendritic cell neoplasms in association with lymphomas and lymphoid proliferations. This is a review of cases with immunohistochemistry for BRAF V600E, with additional immunohistochemistry to categorize tumors. We report the first case of BRAF V600E-positive indeterminate cell tumor in association with angioimmunoblastic T-cell lymphoma. We also report a case of BRAF V600E-positive interdigitating dendritic cell sarcoma in a patient with positive B-cell polymerase chain reaction. It is unclear if these neoplasms developed as transdifferentiation of lymphoid neoplasms or if they developed independently. These cases illustrate the expanding spectrum of BRAF V600E-positive histiocytic and dendritic cell tumors and suggest that attention should be paid to lymphomas for possible coincident presentation of these disorders.

The genetics of interdigitating dendritic cell sarcoma share some changes with Langerhans cell histiocytosis in select cases.

Histiocytic disorders have been noted to have evidence of transdifferentiation; examples of cases with combinations of different lineages have been shown. In our index case, we identified interdigitating dendritic cell (IDC) differentiation in a case of Langerhans cell histiocytosis (LCH). Little is currently known about the genetics of IDC sarcoma (IDCS) because they are exceedingly rare. Using array comparative genomic hybridization (aCGH), we evaluated 4 cases of IDCS and compared them with our index case, as well as genetic abnormalities previously found in LCH. Four cases of paraffin-embedded samples of IDCS and 1 case of LCH with IDC differentiation were evaluated using aCGH. Array CGH results showed no abnormalities in a case of LCH with interdigitating cell differentiation. In 3 of 4 cases of IDCS, genetic abnormalities were identified; 1 case had no identifiable abnormalities. Interdigitating dendritic cell sarcoma case 1 had gains of 3q and 13q; IDCS case 2 had trisomy 12; IDCS case 3 had deletions of 7p, 12p, 16p, 18q, 19q, and 22q; and IDCS case 4 had no detectable abnormalities. Our index case, LCH with IDC differentiation, showed no abnormalities by aCGH. A number of LCH cases do not have detectable genetic abnormalities. In contrast, 3 of 4 cases of IDCS evaluated had identifiable abnormalities by aCGH. Furthermore, 2 of these shared abnormalities, albeit of large genetic regions, with published abnormalities seen in LCH. No recurrent abnormalities were identified in the IDCS cases. However, the possibility of a relationship between IDCS and LCH cannot be entirely excluded by these results.

A Case Presentation of a Rare Pelvic Interdigitating Dendritic Cell Sarcoma.

Sarcoma is a rare type of cancer that arises from connective tissue. Interdigitating dendritic cell sarcoma (IDCS) is a rare neoplasm of dendritic cell origin. IDCS arises from interdigitating dendritic cells found in the T-cell regions of secondary lymphoid tissues. Due to the rare nature of IDCS diagnosis, management can be difficult. Often, the diagnosis is delayed due to a lack of symptoms and signs. Here, we describe a case of a 34-year-old female patient who presented with an incidental finding of a left sidewall pelvic mass later to be confirmed on biopsy as an IDCS.

Primary cutaneous interdigitating dendritic cell sarcoma (IDCS): Report of a new case and literature review.

Interdigitating dendritic cell sarcoma is a very rare entity in the spectrum of histiocytic and dendritic cell neoplasms that mostly occurs in lymph nodes, generally presenting as solitary lymphadenopathy, but may affect every organ. Among extra nodal sites, cutaneous interdigitating dendritic cell sarcoma is exceedingly rare; to date, only 9 cases have been described in English literature. The mean age at diagnosis was 60 years, with a male-female ratio of 1,5 to 1; clinically, two different modalities of skin presentation have been reported: solitary, represented by a single red-brownish nodular lesion, or diffuse, characterized by multiple nodular lesions in one or more body districts. The extreme rarity of this sarcoma and its morphological similarity to other poorly differentiated tumors may lead to a delay in diagnosis; in particular, cutaneous localization may be difficult to differentiate from follicular dendritic cell sarcoma, Langerhans cell sarcoma, poorly differentiated squamous cell carcinoma and more generally sarcomatoid carcinoma, atypical fibroxanthoma, malignant melanoma and several sarcomas. Immunohistochemistry plays an important role in identifying this rare entity and formulating a correct histological diagnosis, fundamental requirement for choosing the best therapeutic approach. We report herein a further case of an 81-year-old Caucasian woman who presented to the Dermatology Department to remove an asymptomatic skin papule in the left temporal region, clinically diagnosed as dermatofibroma. The overall pathological and immunohistochemical features supported the diagnosis of a malignant dendritic cell tumor, consistent of interdigitating dendritic cell sarcoma.

An extremely rare case of interdigitating dendritic cell sarcoma of the parotid gland with a 40­month disease­free survival time after only surgery: A case report.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from dendritic cells and is mainly located in the lymph nodes. To the best of our knowledge, no treatment strategy has yet been established for IDCS, despite its aggressive clinical features. The present study presents the case of a patient with IDCS who experienced a 40-month disease-free survival time after surgery alone. The patient, a 29-year-old woman, presented with a painful right subaural swelling. Diagnostic MRI and 18F-fludeoxyglucose positron emission tomography/computed tomography revealed a right parotid gland tumour and ipsilateral cervical lymph node. The patient underwent surgical resection, and histological examination of the resected tissue specimens confirmed IDCS diagnosis. To the best of our knowledge, this is only the fifth report of an IDCS located in the parotid gland, with the longest follow-up period among cases of IDCS reported in this region. The positive outcome of this patient suggests that surgical resection may be an effective treatment option for local IDCS. Nonetheless, further studies are required to establish a definitive diagnosis and treatment strategy for IDCS.

The Disruption of Retroperitoneal Interdigitating Dendritic Cell Sarcoma with Neurogenic Neoplasm as a Result of Immunohistochemical Markers and Radiological Features.

INTRODUCTION: Retroperitoneal localization is an extremely rare presentation of interdigitating dendritic cell sarcoma (IDCS), the primary neoplasm of the antigen-presenting interdigitating dendritic cells. CASE PRESENTATION: We report an incidentally found isolated retroperitoneal IDCS in a 59-year-old female patient with no prior symptoms. The patient was initially misdiagnosed since the tissue samples obtained by tru-cut biopsies were diffusely positive for S-100, and the radiological features were similar to neurogenic tumors. However, additional immunohistochemical staining in the excisional biopsy specimen revealed IDCS as the correct diagnosis. CONCLUSION: The correct diagnosis may not always be achieved with tru-cut biopsy evaluations in the retroperitoneal masses. Immunophenotyping and radiological features can occasionally be perplexing. In these cases, an accurate diagnosis can be achieved by excisional biopsy and additional immunohistochemical staining.

Interdigitating dendritic cell sarcoma: analysis of two original extra-nodal cases and review of literature.

Interdigitating dendritic cell sarcoma (IDCS) is a rare, highly malignant tumor with a poor prognosis, and current knowledge of this tumor is limited. It is reported that lymph nodes are the primary localization sites. However, in recent years, many primary IDCS have also been reported in the extra-nodal sites, which undoubtedly increases the difficulty of diagnosis. There are very few reports that systematically analyze the clinicopathologic features of IDCS. Here we described two cases of extra-nodal IDCS and reviewed the literature of 44 other published cases of extra-nodal IDCS. Thus, the clinical symptoms, pathological diagnosis, and therapeutic effects of 46 cases of extra-nodal IDCS were summarized in detail. Considering the paucity of available data with regard to IDCS, a thorough and detailed summary would help to better diagnose and treat this neoplasm.

Potential role of MAP2K1 mutation in the trans-differentiation of interdigitating dendritic cell sarcoma: Case report and literature review.

A 5-year-old male child was diagnosed with interdigitating dendritic cell sarcoma (IDCS) during his maintenance therapy for B-cell precursor acute lymphoblastic leukemia (B-ALL). Multiplex lymph node involvements of the neck were found by positron emission tomography CT (PET-CT). Treatments, including surgical and chemotherapy, resulted in complete remission. Four years later, systemic bone infiltration was discovered. Surgical resection of the IV rib and intensive chemotherapy led to a complete morphological remission, and allogeneic bone marrow transplantation was performed. Comprehensive genomic profiling of the formalin fixed the tumor tissue, and the cryopreserved leukemic cells revealed several common alterations and divergent clonal evolution with a novel MAP2K1 mutation of the IDCS, which is responsible for the trans-differentiation of the common lymphoid-committed tumor progenitor.

Interdigitating Dendritic Cell Sarcoma of the Small Intestine Presenting as Spontaneous Hemoperitoneum - A Rare Case Report.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from the antigen-presenting cells of the immune system. It usually involves the lymph nodes, and extranodal sites are rarely affected. Here, we report a first known case of spontaneous hemoperitoneum caused by the rupture of IDCS of the small bowel. A 61-year-old male presented with complaints of abdominal pain and fever for 3 days and breathlessness for 1 day. Ultrasound abdomen revealed a 15 cm × 7 cm heterogeneous collection with thick septations in the periumbilical region. Diagnostic peritoneal lavage revealed hemoperitoneum and gangrenous bowel. Emergency laprotomy was done and it revealed a friable mass arising from the ileum. Resection of 2 ft of the ileum and double-barrel ileostomy was done. Immunohistochemical analysis revealed a positivity of S100 and leukocyte common antigen). A diagnosis of IDCS was made. The patient had an uneventful postoperative recovery and planned for postoperative chemotherapy.

Interdigitating dendritic cell sarcoma of pleura, diagnostic challenges of a rare disease.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare subtype of dendritic cell tumour. The solitary lymph node disease is most commonly seen, but may occasionally present extranodally in skin, intestines, soft tissue, liver or spleen. Here we present a case of IDCS in pleura in 53-year-old man, who presented with loss of appetite and chest pain. The initial biopsy was inconclusive. The patient was started on anti-tubercular treatment considering the higher prevalence of the disease in this part of the world. However, the symptoms worsened after 2 months and repeat PET-CT scan revealed extensive FDG avid lesions in the multiple sites in the body. Repeat PET guided biopsy confirmed this rare IDCS neoplasm. Diagnostic challenges of this rare tumour are discussed.

A case report of interdigitating dendritic cell sarcoma originating from the oropharynx.

Interdigitating dendritic cell sarcoma is an extremely rare tumor and typically originates from lymph nodes. Here, we report a patient with tumor originated from the oropharynx who received successful surgical treatment.

Interdigitating dendritic cell sarcoma located in the adrenal gland: a case report and literature review.

We report a case of interdigitating dendritic cell sarcoma (IDCS) originating from the adrenal gland. A 57-year-old middle-aged woman with no previous history of malignancy came to our hospital after color Doppler ultrasound revealed a right adrenal mass. An abdominal computed tomography scan also showed an adrenal mass. Postoperative pathology confirmed the diagnosis of IDCS. After complete surgical removal of the adrenal tumor, the patient has been disease-free for 1 year. IDCS may have a good prognosis after surgical resection. To our knowledge, this is only the second reported case of IDCS in the adrenal region.

Histiocytic and Dendritic Cell Neoplasms.

Histiocytic and dendritic cell neoplasms are very rare, belonging to a group that share morphologic, immunophenotypic, and ultrastructural characteristics of mature histiocytic/dendritic neoplasms. Histiocytic and dendritic cell neoplasms may arise de novo or in association with B-cell, T-cell, or myeloid neoplasms. Recent molecular findings, particularly the discoveries of the mutations in the RAS-RAF-MEK-ERK pathway, have greatly advanced the diagnosis and treatment options. Histiocytic and dendritic cell neoplasms may closely resemble each other, non-hematopoietic neoplasms, and even reactive processes. Therefore, it is essential to understand the clinicopathologic characteristics, differential diagnoses, and pitfalls of each entity.