Blastic Plasmacytoid Dendritic Cell Neoplasm with Extensive Cutaneous and Central Nervous System Involvement

Blastic plasmacytoid dendritic neoplasm is an exceedingly rare tumor that has undergone several changes in nomenclature over the last two decades, largely because of confusion regarding its cell of origin. It does, however, have distinctive clinical features with a particularly aggressive clinical course and no standard treatment. Overall, prognosis is poor and relapse is routine after initial response to chemotherapy. In this report, we describe a typical patient with this disease and reconcile the available literature and its evolution. We emphasize the leukemic nature of this tumor\u27s behavior, with extensive central nervous system and skin involvement, and describe for the first time a potential role for maintenance chemotherapy in its treatment

Metastatic Angiosarcoma and Kasabach-Merritt Syndrome

Angiosarcomas are exceedingly rare tumors that are often difficult to diagnose. Exceptionally unusual is the presentation of these tumors with Kasabach-Merritt Syndrome, a curious form of intratumoral coagulation that can be impossible to distinguish from intravascular coagulation, which is more common. Instant recognition of this clinical association can help making a prompt diagnosis and timely initiation of therapy

ErbB3 downregulation enhances luminal breast tumor response to antiestrogens

Aberrant regulation of the erythroblastosis oncogene B (ErbB) family of receptor tyrosine kinases (RTKs) and their ligands is common in human cancers. ErbB3 is required in luminal mammary epithelial cells (MECs) for growth and survival. Since breast cancer phenotypes may reflect biological traits of the MECs from which they originate, we tested the hypothesis that ErbB3 drives luminal breast cancer growth. We found higher ERBB3 expression and more frequent ERBB3 gene copy gains in luminal A/B breast cancers compared with other breast cancer subtypes. In cell culture, ErbB3 increased growth of luminal breast cancer cells. Targeted depletion of ErbB3 with an anti-ErbB3 antibody decreased 3D colony growth, increased apoptosis, and decreased tumor growth in vivo. Treatment of clinical breast tumors with the antiendocrine drug fulvestrant resulted in increased ErbB3 expression and PI3K/mTOR signaling. Depletion of ErbB3 in fulvestrant-treated tumor cells reduced PI3K/mTOR signaling, thus decreasing tumor cell survival and tumor growth. Fulvestrant treatment increased phosphorylation of all ErbB family RTKs; however, phospho-RTK upregulation was not seen in tumors treated with both fulvestrant and anti-ErbB3. These data indicate that upregulation of ErbB3 in luminal breast cancer cells promotes growth, survival, and resistance to fulvestrant, thus suggesting ErbB3 as a target for breast cancer treatment

ErbB3 downregulation enhances luminal breast tumor response to antiestrogens

Aberrant regulation of the erythroblastosis oncogene B (ErbB) family of receptor tyrosine kinases (RTKs) and their ligands is common in human cancers. ErbB3 is required in luminal mammary epithelial cells (MECs) for growth and survival. Since breast cancer phenotypes may reflect biological traits of the MECs from which they originate, we tested the hypothesis that ErbB3 drives luminal breast cancer growth. We found higher ERBB3 expression and more frequent ERBB3 gene copy gains in luminal A/B breast cancers compared with other breast cancer subtypes. In cell culture, ErbB3 increased growth of luminal breast cancer cells. Targeted depletion of ErbB3 with an anti-ErbB3 antibody decreased 3D colony growth, increased apoptosis, and decreased tumor growth in vivo. Treatment of clinical breast tumors with the antiendocrine drug fulvestrant resulted in increased ErbB3 expression and PI3K/mTOR signaling. Depletion of ErbB3 in fulvestrant-treated tumor cells reduced PI3K/mTOR signaling, thus decreasing tumor cell survival and tumor growth. Fulvestrant treatment increased phosphorylation of all ErbB family RTKs; however, phospho-RTK upregulation was not seen in tumors treated with both fulvestrant and anti-ErbB3. These data indicate that upregulation of ErbB3 in luminal breast cancer cells promotes growth, survival, and resistance to fulvestrant, thus suggesting ErbB3 as a target for breast cancer treatment

Blastic plasmacytoid dendritic cell neoplasm with extensive cutaneous and central nervous system involvement

Blastic plasmacytoid dendritic neoplasm is an exceedingly rare tumor that has undergone several changes in nomenclature over the last two decades, largely because of confusion regarding its cell of origin. It does, however, have distinctive clinical features with a particularly aggressive clinical course and no standard treatment. Overall, prognosis is poor and relapse is routine after initial response to chemotherapy. In this report, we describe a typical patient with this disease and reconcile the available literature and its evolution. We emphasize the leukemic nature of this tumor’s behavior, with extensive central nervous system and skin involvement, and describe for the first time a potential role for maintenance chemotherapy in its treatment

Metastatic angiosarcoma and Kasabach-Merritt syndrome

Angiosarcomas are exceedingly rare tumors that are often difficult to diagnose. Exceptionally unusual is the presentation of these tumors with Kasabach-Merritt Syndrome, a curious form of intratumoral coagulation that can be impossible to distinguish from intravascular coagulation, which is more common. Instant recognition of this clinical association can help making a prompt diagnosis and timely initiation of therapy