Search

Blastic plasmacytoid dendritic cell neoplasm is a malignant, aggressive, and rare tumor arising from plasmacytoid dendritic cell precursors. Because of its infrequency, information on clinical features and best treatment options is still lacking. Dermatoscopic features on this entity have only been reported in a few cases so far. Therefore, we describe a new case and review published data on this topic. [ABSTRACT FROM AUTHOR]

A 72-year-old man with a history of squamous cell carcinoma presented to the Portland VA with forehead discoloration. He was initially diagnosed with actinic damage and prescribed topical treatment. However, he returned to clinic months later with a large, violaceous forehead plaque. Upon biopsy, he was diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare hematological malignancy. This case report illustrates the importance of keeping BPDCN in the differential diagnosis for ecchymotic plaques that fail to respond to first line therapy.

Abstract Background Prostate cancer is a common cancer in men that annually results in more than 33 000 US deaths. Mortality from prostate cancer is largely from metastatic disease, reflecting on the great strides in the last century of treatments in care for the localized disease. Metastatic castrate resistant prostate cancer (mCRPC) will commonly travel to the bone, creating unique bone pathology that requires nuanced treatments in those sites with surgical, radio and chemotherapeutic interventions. The bone morphogenetic protein (BMP) pathway has been historically studied in the capacity to regulate the osteogenic nature of new bone. New mineralized bone generation is a frequent and common observation in mCRPC and referred to as blastic bone lesions. Less common are bone destructive lesions that are termed lytic. Methods We queried the cancer genome atlas (TCGA) prostate cancer databases for the expression of the BMP pathway and found that distinct gene expression of the ligands, soluble antagonists, receptors, and intracellular mediators were altered in localized versus metastatic disease. Human prostate cancer cell lines have an innate ability to promote blastic‐ or lytic‐like bone lesions and we hypothesized that inhibiting BMP signaling in these cell lines would result in a distinct change in osteogenesis gene expression with BMP inhibition. Results We found unique and common changes by comparing these cell lines response and unique BMP pathway alterations. We treated human PCa cell lines with distinct bone pathologic phenotypes with the BMP inhibitor DMH1 and found distinct osteogenesis responses. We analyzed distinct sites of metastatic PCa in the TCGA and found that BMP signaling was selectively altered in commons sites such as lymph node, bone and liver compared to primary tumors. Conclusions Overall we conclude that BMPs in metastatic prostate cancer are important signals and functional mediators of diverse processes that have potential for individualized precision oncology in mCRPC.

From the 33,000 men in the U.S. who die from prostate cancer each year, the majority of these patients exhibit metastatic disease with bone being the most common site of metastasis. Prostate cancer bone metastases are commonly blastic, exhibiting new growth of unhealthy sclerotic bone, which can cause painful skeletal related events. Patient’s current care entails androgen deprivation therapy, anti-resorptive agents, radiation, and chemotherapy to help control the spread of the cancer but little intervention is available to treat blastic bone disease. The transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) pathways are known to regulate bone growth and resorption of destructive lytic bone lesions, yet the role of TGFβ/BMP signaling in prostate cancer blastic vs lytic bone lesions are not fully understood. We hypothesized that to target the BMP/TGFβ pathway, a useful biomarker of bone lytic or blastic pathology would have superior response. We show distinct BMP vs. TGFβ signaling in clinical samples of human prostate cancer bone metastases with either lytic or blastic pathologies. BMPs exhibit distinct effects on bone homeostasis, so to examine the effect of BMP inhibition on healthy bone, we treated mice with the BMP receptor small molecule antagonist DMH1 and saw a modest temporary improvement in bone health, with increased trabecular bone. We next sought to use the BMP inhibitor DMH1 to treat bone metastasis engraftment seeded by a caudal artery injection of the lytic human prostate cell line PC3 in immunodeficient mice. The colonization by PC3 cells to the bone were restricted with DMH1 treatment and bone health was importantly preserved. We next proceeded to test BMP inhibition in an injury model of established bone metastasis via intratibial injection of the MYC-CaP mouse prostate cell line into FVBN syngeneic mice. DMH1 treated mice had a modest decrease in trabecular bone and reduced lymphocytes in circulation without affecting tumor growth. Taken together we show unique responses to BMP inhibition in metastatic prostate cancer in the bone. These studies suggest that profiling bone lesions in metastatic prostate cancer can help identify therapeutic targets that not only treat the metastatic tumor but also address the need to better treat the distinct tumor induced bone disease.

From the 33,000 men in the U.S. who die from prostate cancer each year, the majority of these patients exhibit metastatic disease with bone being the most common site of metastasis. Prostate cancer bone metastases are commonly blastic, exhibiting new growth of unhealthy sclerotic bone, which can cause painful skeletal related events. Patient's current care entails androgen deprivation therapy, anti-resorptive agents, radiation, and chemotherapy to help control the spread of the cancer but little intervention is available to treat blastic bone disease. The transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) pathways are known to regulate bone growth and resorption of destructive lytic bone lesions, yet the role of TGFβ/BMP signaling in prostate cancer blastic vs lytic bone lesions are not fully understood. We hypothesized that to target the BMP/TGFβ pathway, a useful biomarker of bone lytic or blastic pathology would have superior response. We show distinct BMP vs. TGFβ signaling in clinical samples of human prostate cancer bone metastases with either lytic or blastic pathologies. BMPs exhibit distinct effects on bone homeostasis, so to examine the effect of BMP inhibition on healthy bone, we treated mice with the BMP receptor small molecule antagonist DMH1 and saw a modest temporary improvement in bone health, with increased trabecular bone. We next sought to use the BMP inhibitor DMH1 to treat bone metastasis engraftment seeded by a caudal artery injection of the lytic human prostate cell line PC3 in immunodeficient mice. The colonization by PC3 cells to the bone were restricted with DMH1 treatment and bone health was importantly preserved. We next proceeded to test BMP inhibition in an injury model of established bone metastasis via intratibial injection of the MYC-CaP mouse prostate cell line into FVBN syngeneic mice. DMH1 treated mice had a modest decrease in trabecular bone and reduced lymphocytes in circulation without affecting tumor growth. Taken together we show unique responses to BMP inhibition in metastatic prostate cancer in the bone. These studies suggest that profiling bone lesions in metastatic prostate cancer can help identify therapeutic targets that not only treat the metastatic tumor but also address the need to better treat the distinct tumor induced bone disease. [ABSTRACT FROM AUTHOR]

Objectives: To compare the concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation.Materials and methods: Retrospective review of 215 FNAs of osseous lesions performed in conjunction with core biopsy at our institution over a 6-year period (2011-2016). FNAs were interpreted independently of core biopsies. We assessed if FNA in conjunction with core biopsy increased diagnostic accuracy compared to core biopsy alone. We also calculated the concordance between FNA and core biopsy by lesion appearance, lesion CT attenuation, lesion histology, lesion location and FNA needle gauge size.Results: Core biopsy alone provided the diagnosis in 207/215 cases (96.3%), however, the FNA provided the diagnosis in the remaining 8/215 cases (3.7%) where the core biopsy was non-diagnostic. There were 154 (71.6%) lytic lesions, 21 (9.8%) blastic lesions, 25 (11.6%) mixed lytic and blastic lesions and 15 (7.0%) lesions that were neither lytic nor blastic. The concordance between FNA and core biopsy for lytic osseous lesions (136/154 cases, 88.3%) was statistically significantly higher than that for blastic osseous lesions (13/21 cases, 61.9%) [P = 4.2 × 10−3; 95% CI (0.02, 0.50)]. The concordance between FNA and core biopsy was higher for low-attenuation- (110/126) than high-attenuation (58/77) lesions (P = 0.028). The concordance between FNA and core biopsy was also higher for metastases (102/119 cases, 85.7%) than non-metastases (78/96, 81.3%) [P = 0.487; 95% CI (− 0.15, 0.065)]. There was no difference in the rate of concordance between FNA and core biopsy by lesion location or FNA needle gauge size (P > 0.05).Conclusion: FNA with core biopsy increases diagnostic rate compared to core biopsy alone or FNA alone. The concordance between FNA and core biopsy is higher for lytic lesions than for blastic lesions; and higher for low-attenuation lesions than for high-attenuation lesions. [ABSTRACT FROM AUTHOR]

Primary cutaneous marginal zone lymphoma (PCMZL) is a form of indolent lymphoproliferative disease where the disease is largely a cutaneous confined process. It is typically a neoplasm composed of post germinal small B-cells and light chain restricted plasma cells in a background of reactive T-cell hyperplasia and benign germinal centers. Rarely a significant degree of large cell infiltration occurs warranting the categorization as blastic marginal zone lymphoma. We reviewed our data base over a time period of 2016 to 2022 for cases diagnosed as blastic MZL. Twelve cases were identified. The clinical records and pathological data were reviewed. Nine of the cases represented de novo forms of blastic MZL while in three cases there was a prior history of MZL. Multifocal cutaneous disease was not uncommon and one quarter of the cases had evidence of extracutaneous dissemination. All patients except three achieved remission with varied therapeutic interventions depending on the extent of the disease ranging from conservative re-excision to chemotherapy. No patient died from lymphoma. Light microscopically, there was evidence of a background of conventional MZL in the majority of cases. The large cell component was typically characterized by multiple micronodular aggregates throughout the dermis although in three cases there was a striking diffuse large cell component as the dominant infiltrate. Phenotypically, a third of the cases showed either CD5 or CD23 positivity amidst neoplastic B cells. Significant staining for BCL-2 was noted in the majority of cases tested while extensive MUM-1 positivity was observed in half of the cases tested. Kappa or lambda light chain restriction was seen in most. The Ki67 proliferation index exceeded 30 % in all cases. There was C-MYC positivity in two cases. While most cases did not detect cytogenetic abnormalities, one case had multiple cytogenetic hits that are associated with diffuse large B cell lymphoma. Next generation sequencing showed a Ten-eleven translocation 2 mutation in the earlier biopsy prior to transformation and in the later biopsy after transformation along with an additional B2M mutation in the transformed biopsy. Both types of mutations are very uncommon but held to contribute to tumor progression in the setting of diffuse large B cell lymphoma. Blastic MZL is associated with a more aggressive clinical course. Even when there is disseminated disease patients while not always cured did not have a fatal course in this series. The light microscopic findings are reproducible. The background of MZL, identification of larger cells in significant numbers without a follicle center phenotype, at times expressing CD5 or CD23 with variable positivity for MUM1, BCL-2 and C-MYC and a high proliferation index define the pathology in most. Certain cytogenetic abnormalities and genetic mutations implicated in large cell transformation into a diffuse large B cell lymphoma are seen in blastic MZL with earlier biopsies prior to transformation potentially harboring at risk genetic mutations. • blastic • marginal • zone • lymphoma • extracutaneous dissemination [ABSTRACT FROM AUTHOR]

A 66-year-old man developed a slowly enlarging, bilateral, painless, periorbital, and orbital swelling with ptosis, nonaxial proptosis, chemosis, exposure keratopathy, and decreased vision in both eyes. He had fever, night sweats, and weight loss (B-symptoms), along with lymphadenopathy and elevated serum lactate dehydrogenase, with no prior history of lymphoma. A transpalpebral incisional biopsy revealed a rare case of mantle-cell lymphoma of blastoid variant, stage IVB. The main immunophenotype characteristics were cyclin D1+, CD5+, CD10−, CD23−, Bcl-6−/+, and a high (up to 80%) Ki-67 proliferation index. Following an excellent response to the immune-chemotherapy treatment plan, all ocular adnexal lymphoma manifestations disappeared completely; however, 13 months after the initial presentation, there was a recurrence of the disease with rapid worsening and death. The blastoid variant of mantle cell lymphoma, a rare subtype of mantle-cell lymphoma, is a highly aggressive neoplasm, ultimately having a fatal outcome. As the initial manifestation of the disease, ocular adnexal region blastoid variant of mantle-cell lymphoma is an exceptional event, with only one previous case reported. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematological tumor originating from the precursor of plasmacytoid dendritic cells (pDCs) with a persistent and progressive course of illness. Despite being an aggressive disease BPDCN has an initial indolent course manifested as skin lesions. Alongside or following the skin lesion, the extra-cutaneous manifestation develops and includes lymphadenopathy, splenomegaly, and hepatomegaly. The BPDCN diagnosis is mainly based on the immunophenotype.  Herein, we report the case of a 72-year-old male patient who presented with a history of left anterior chest wall painless skin lesions. Histology of skin biopsy of the left chest skin lesion showed diffuse dermal infiltration by monomorphic medium-sized blastic cells positive for cluster of differentiation (CD)4, CD45, CD7, CD56, CD43, CD123, T-cell leukemia-1 (TCL1), and B-cell leukemia/lymphoma 2 protein (BCL2). Given the rarity of the disease, standard chemotherapy regimens used in treating different leukemias and lymphomas have been adapted to treat BPDCN., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nasiri et al.)

Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy derived from precursors of plasmacytoid dendritic cells. Nearly all patients present initially with cutaneous manifestations, with many having extracutaneous disease additionally. While response to chemotherapy initially is effective, relapse occurs in most, with a leukemic phase ultimately developing. The prognosis is dismal. While most of the clinical and pathologic features are well described, the association and possible prognostic significance between peripheral blood absolute monocytosis (>1.0 K/μL) and blastic plasmacytoid dendritic cell neoplasm have not been reported. We report a case of a 68-year-old man who presented with a rash for 4-5 months. On physical examination, there were multiple, dull-pink, indurated plaques on the trunk and extremities. Complete blood count revealed thrombocytopenia, absolute monocytosis of 1.7 K/μL, and a negative flow cytometry study. Biopsy of an abdominal lesion revealed typical features of blastic plasmacytoid dendritic cell neoplasm. Patients having both hematologic and nonhematologic malignancies have an increased incidence of absolute monocytosis. Recent studies examining Hodgkin and non-Hodgkin lymphoma patients have suggested that this is a negative prognostic factor. The association between blastic plasmacytoid dendritic cell neoplasm and absolute monocytosis has not been described and may, in fact, have prognostic value. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cell (PDC) is a Th2-type dendritic cell precursor. It is an important professional effector cell characterized by its capacities to produce large amount of alpha interferon and to differentiate into dendritic cell. PDCs are scarce in normal condition. They circulate in the blood as veiled cells and enter the lymph node and mucosal site in response to immune stimulation. Besides the recent and wide-open field of the implication of PDCs in inflammatory diseases and in the microenvironment of solid or lymphoid tumours it has also been observed that PDCs can also be tumoral cells. In this paper, the authors present the different tumours thought to be originating from tumoral PDCs. To date, two kinds of tumoral conditions are recognized: the so-called PDCs proliferations in patients with myeloid disorders and the blastic plasmacytoid dendritic cell neoplasm. These two entities are exposed and discussed. [ABSTRACT FROM AUTHOR]

In 1969, specialists at the Kananaskis hyphomycete workshop coined the terms 'blastic' and 'thallic' to describe two distinct modes of conidiogenesis. Since then, the original concepts have been slightly modified and redefined, and the terms have been widely adopted in taxonomic descriptions of conidial fungi. Problems arise in the application of these terms to conidial development in fungi which demonstrate morphological plasticity ranging from fragmentation of a hypha to extrusion of a portion of a hypha or cell. A number of fungi, such as anamorphs of Onygenales which includes many of the fungi pathogenic to man, demonstrate intergradations between blastic and thallic development. Because development in this group of fungi is difficult to categorize, it has led to an inconsistent treatment of taxa which share many other developmental features in common. In using these terms, it should be remembered that they represent extremes in a developmental spectrum. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive tumour derived from the precursors of plasmacytoid dendritic cells with a high frequency of cutaneous and bone marrow involvement and leukemic dissemination. This entity is a diagnostic challenge due to its morphological overlap with cutaneous lymphoma or secondary cutaneous involvement by myeloid leukemia. We report a 71-year-old man who initially presented with scalp lesions, extending to chest and back with rapid increase in size and number. These lesions were mildly pruritic but non-painful and there was no history of previous similar skin rashes. He was otherwise asymptomatic. An initial skin biopsy was reported as atypical lymphocytic infiltrate suspicious for lymphoproliferative disorder. Histopathology of a second skin punch biopsy specimen and immunohistochemistry at our institution demonstrated that the tumour cells were intermediate-sized with irregularly shaped nuclei with fine, immature chromatin and blastoid morphology. Based on a large immunohistochemical panel, cells were positive for CD4, CD43, CD2, CD56, CD33, TdT and CD123 and negative for CD20, CD3, CD5, PAX5, CD138, CD34, CD68, CD30, CD117, EBER-ISH, TIA-1, lysozyme and myeloperoxidase. The patient was subsequently treated with hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone followed by intrathecal methotrexate and cytarabine) chemotherapy and is currently in remission. This diagnosis is rendered difficult owing to common morphological overlaps and rarity of this malignancy. These neoplasms are highly aggressive, therefore; strong suspicion and detection will help in early therapeutic interventions and may have a significant impact on patient's survival. [ABSTRACT FROM AUTHOR]

BPDCN is a recently elucidated clinicopathologic entity. This disease typically involves the skin, with 30% to 40% of patients showing an additional concurrent leukemic component. Although BPDCN often exhibits cytologic features akin to acute lymphoblastic leukemia, the main differential diagnostic challenge, in the skin and in the bone marrow, is distinction from AML, in particular AML with monocytic differentiation., (Copyright © 2013 Elsevier Inc. All rights reserved.)