Contributions
Type: Publication Only
Background
Extramedullary (EM) plasmacytoma is a plasma cell neoplasm of the soft tissues that may occur with or without bone marrow and systemic involvement. EM disease is an uncommon manifestation in Multiple Myeloma (MM) and can either accompany newly diagnosed disease or more frequently develop with relapse. It seems to have a different pathogenesis from the medullary involvement and represents an independent poor prognostic factor with high rate of mortality. Myeloma of the breast is a rare entity not completely understood, with only a few reported cases in the literature not providing any statistical information.
Aims
We present a patient with extramedullary breast plasmacytoma diagnosed incidentally during breast plastic surgery for long-term history of fibrocystic disease. This unexpected diagnosis was shortly thereafter followed by a severe systemic medullary and extramedullary recurrence, treated with chemotherapy and radiotherapy.
Methods
A 44 year-old woman was diagnosed with IgG lambda MM stage IIIA ISS3, showing deletion of 17 and 13 chromosome detected by FISH and without bone or EM lesions. She was affected by MGUS from 14 years and had undergone right nephrectomy for renal cancer five years before. VTD therapy was started (total 4 cycles) followed by double autologous HSCT obtaining a VGPR. She remained in remission of disease for 14 months until mastopexy breast surgery. Surprisingly the histopathological examination of the breast tissue was consistent with diagnosis of plasmacytoma. Strangely, both the ultrasound and the breast MRI showed no nodular areas. Molecular examination confirmed the presence of monoclonal lambda positive plasma cells achieved through analysis of the rearrangement of the immunoglobulin heavy chain genes by PCR.
Results
A subsequent disease restaging showed an unexpected massive skeletal bone marrow and extramedullary involvement. PET/CT revealed pathological accumulation in the femoral heads, left iliac bone, gluteal muscles, pelvis. X-rays demonstrated multiple lytic lesions of right and left humerus, pelvis and D2 vertebral wall. MRI showed massive effusion in the left iliac bone with multiple lytic lesions extending up to gluteal muscles. She presented high level of LDH and 30% of atypical bone marrow CD56 negative plasma cells. She underwent radiotherapy on her pelvis and was treated according with PAD regimen (4 cycles). Nowadays patient is currently undergoing therapy; autologous and allogenetic HSCT are being evaluated.
Summary
EM is prevalent in genomically defined high-risk MM with shorter overall survival. Some autopsy studies have shown extraskeletal involvement in approximately 50-70% of patients with MM. EM disease seems to be prevalent in patients treated with novel agents, although this finding is not confirmed and could be due to the increased survival of patients with new drugs. The mechanisms of extramedullary spread are poorly understood; a decreased expression of integrins and loss of CD56 have been described, which could cause disease dissemination. Several papers have described relapses of MM occurring from different subclones of plasma cells from those of initial diagnosis. Recently, it has been speculated the presence of Circulating Myeloma Tumor Cells (CTCs), that constitute a subpopulation of clonal plasma cells associated with aggressive disease. They are characterized by downregulation of adhesion molecules, might transit in the peripheral blood and colonize other sites during the patients’ resting and remission period. One might ask some questions: some recurrent MM could be firstly an awakening of dormant MM circulating clones? Which are the mechanisms for hematogenous spread and EM involvement? These and others are unanswered questions; international collaborative trials are necessary to better understand EM dissemination and discover optimal treatment.
Keyword(s): Breast, Clonal expansion, Multiple myeloma, Plasma cells
Session topic: Publication Only
Type: Publication Only
Background
Extramedullary (EM) plasmacytoma is a plasma cell neoplasm of the soft tissues that may occur with or without bone marrow and systemic involvement. EM disease is an uncommon manifestation in Multiple Myeloma (MM) and can either accompany newly diagnosed disease or more frequently develop with relapse. It seems to have a different pathogenesis from the medullary involvement and represents an independent poor prognostic factor with high rate of mortality. Myeloma of the breast is a rare entity not completely understood, with only a few reported cases in the literature not providing any statistical information.
Aims
We present a patient with extramedullary breast plasmacytoma diagnosed incidentally during breast plastic surgery for long-term history of fibrocystic disease. This unexpected diagnosis was shortly thereafter followed by a severe systemic medullary and extramedullary recurrence, treated with chemotherapy and radiotherapy.
Methods
A 44 year-old woman was diagnosed with IgG lambda MM stage IIIA ISS3, showing deletion of 17 and 13 chromosome detected by FISH and without bone or EM lesions. She was affected by MGUS from 14 years and had undergone right nephrectomy for renal cancer five years before. VTD therapy was started (total 4 cycles) followed by double autologous HSCT obtaining a VGPR. She remained in remission of disease for 14 months until mastopexy breast surgery. Surprisingly the histopathological examination of the breast tissue was consistent with diagnosis of plasmacytoma. Strangely, both the ultrasound and the breast MRI showed no nodular areas. Molecular examination confirmed the presence of monoclonal lambda positive plasma cells achieved through analysis of the rearrangement of the immunoglobulin heavy chain genes by PCR.
Results
A subsequent disease restaging showed an unexpected massive skeletal bone marrow and extramedullary involvement. PET/CT revealed pathological accumulation in the femoral heads, left iliac bone, gluteal muscles, pelvis. X-rays demonstrated multiple lytic lesions of right and left humerus, pelvis and D2 vertebral wall. MRI showed massive effusion in the left iliac bone with multiple lytic lesions extending up to gluteal muscles. She presented high level of LDH and 30% of atypical bone marrow CD56 negative plasma cells. She underwent radiotherapy on her pelvis and was treated according with PAD regimen (4 cycles). Nowadays patient is currently undergoing therapy; autologous and allogenetic HSCT are being evaluated.
Summary
EM is prevalent in genomically defined high-risk MM with shorter overall survival. Some autopsy studies have shown extraskeletal involvement in approximately 50-70% of patients with MM. EM disease seems to be prevalent in patients treated with novel agents, although this finding is not confirmed and could be due to the increased survival of patients with new drugs. The mechanisms of extramedullary spread are poorly understood; a decreased expression of integrins and loss of CD56 have been described, which could cause disease dissemination. Several papers have described relapses of MM occurring from different subclones of plasma cells from those of initial diagnosis. Recently, it has been speculated the presence of Circulating Myeloma Tumor Cells (CTCs), that constitute a subpopulation of clonal plasma cells associated with aggressive disease. They are characterized by downregulation of adhesion molecules, might transit in the peripheral blood and colonize other sites during the patients’ resting and remission period. One might ask some questions: some recurrent MM could be firstly an awakening of dormant MM circulating clones? Which are the mechanisms for hematogenous spread and EM involvement? These and others are unanswered questions; international collaborative trials are necessary to better understand EM dissemination and discover optimal treatment.
Keyword(s): Breast, Clonal expansion, Multiple myeloma, Plasma cells
Session topic: Publication Only