Tumor-like Lesions with B cell predominance Flashcards
27 year old male with history of type 1 diabetes mellitus presents with cervical lymphadenopathy for the past three months.
Unicentric Castleman disease - Hyaline vascular subtype
The lymph node shows enlarged follicles with hyalinized blood vessels leading into germinal centers surrounded by concentric rings of prominent mantle zone cells with an “onion skin” appearance.
Follicles with two germinal centers (twinning, shown) or involuted germinal centers with increased follicular dendritic cells and clusters of plasmacytoid dendritic cells may be seen.
Background contains polytypic B and T cells, FDCs, and plasmacytoid DCs.
Treated with surgical excision. Excellent prognosis.
56 year old male with history of type 1 diabetes mellitus presents with cervical lymphadenopathy for the past three months.
Unicentric Castleman disease - Plasma cell subtype
Overall, the lymph node architecture is preserved, however follicles have hyperplastic germinal centers and the interfollicular areas are filled with sheets of plasma cells and have prominent vasculature.
Caused by dysregulation of IL-6. Patients may have cytopenias, but not to the extent of a bone marrow infiltrative process.
Bakground polytypic B and T cells. HHV8 LANA negative, EBER ISH negative.
Treated with surgical excision. Excellent prognosis.
50 year-old male presents with several weeks of fever and malaise. On exam, he is found to have significant edema in all extremities as well as facial edema. Blood counts show a mild anemia and significant thrombocytopenia, as well as mild renal dysfunction. CT chest/abdomen/pelvis shows splenomegaly, hepatomegaly, and enlargement of the cervical, mediastinal, and left inguinal lymph nodes. A left inguinal node is biopsied.
Idiopathic Multicentric Castleman Disease - TAFRO subtype
iMCD by definition has involvement of two or more lymph node sites, as well as a syndrome of hypercytokinemia. Subtyped into iMCD-TAFRO (thrombocytopenia, anasarca, fever/inflammatory symptoms, renal dysfunction/marrow reticulin fibrosis, organomegaly) and iMCD-NOS.
Manifests across all age groups, median age ~50 years. Male:female ratio about even. Etiology unknown, but thought to be inflammatory, neoplastic, or viral factors.
Criteria:
1. Enlarged lymph nodes in more than two sites.
2. Lymph node morphology showing grade 2 or 3 regressed germinal centers or plasmacytosis.
3. Clinical, laboratory, and exclusion criteria fulfilled
Morphologically, grade 2 or 3 regressed GCs or plasmacytosis are required for diagnosis. Marrow of patients with iMCD-TAFRO commonly show hypercellularity with megakaryocytic hyperplasia, clustering, and increased reticulin fibers.
To make a diagnosis of iMCD, HHV8 LANA1 must be negative.
iMCD-TAFRO has a more aggressive prognosis with short survival. There is still no definitive therapy for these cases, but IL-6 antagonists and mTOR inhibitors are the current options.
50 year-old male presents with several weeks of fever and malaise. On exam, he is found to have large cervical lymphadenopathy. Blood counts show significant thrombocytosis. CT chest/abdomen/pelvis show substantial cervical, mediastinal, and retroperitoneal lymphadenopathy. A cervical lymph node is biopsied.
Idiopathic Multicentric Castleman Disease - NOS
iMCD by definition has involvement of two or more lymph node sites, as well as a syndrome of hypercytokinemia. Subtyped into iMCD-TAFRO (thrombocytopenia, anasarca, fever/inflammatory symptoms, renal dysfunction/marrow reticulin fbirosis, organomegaly) and iMCD-NOS.
Manifests across all age groups, median age ~50 years. Male:female ratio about even. Etiology unknown, but thought to be inflammatory, neoplastic, or viral factors.
Criteria:
1. Enlarged lymph nodes in more than two sites.
2. Lymph node morphology showing grade 2 or 3 regressed germinal centers or plasmacytosis.
3. Clinical, laboratory, and exclusion criteria fulfilled
Patients without the TAFRO phenotype most often exhibit larger lymphadenopathy, thrombocytosis, and polyclonal hypergammaglobulinemia.
Morphologically, grade 2 or 3 regressed GCs or plasmacytosis are required for diagnosis. Compared to TAFRO, NOS cases often feature more interfollicular plasma cells and fewer atrophic follicles.
Marrow of patients with iMCD-NOS commonly show plasmacytosis with increased megakaryocytes.
To make a diagnosis of iMCD, HHV8 LANA1 must be negative.
iMCD-NOS has a more favorable prognosis than iMCD-TAFRO. There is still no definitive therapy for these cases, but IL-6 antagonists and mTOR inhibitors are the current options.
IgG4-related disease
Rosai Dorfman disease
Despite looking inflammatory, this is a neoplasm. The neoplastic cells are the histiocytes, and approximately 1/3 of these patients harbor gene mutations involving the MAPK/ERK pathway, e.g., NRAS, KRAS, MAP2K1, and, rarely, the BRAF mutation.
IHC: In addition to classical macrophage markers (S100/fascin/CD68/CD163) histiocytes in RDD also express BCL-1 and OCT2.
