Grading of follicular lymphoma: comparison of routine histology with immunohistochemistry.

CONTEXT: Follicular lymphoma (FL) grading is based on the average number of large transformed cells in 10 neoplastic follicles at x40 high-power field (x10-40 high-power field) examination (grade 1, 0-5 centroblasts per high-power field; grade 2, 6-15 centroblasts per high-power field; grade 3, >15 centroblasts per high-power field). OBJECTIVE: Since there may be significant interobserver variability, we analyzed the usefulness of immunohistochemical stains in grading FLs more reliably. DESIGN: Forty-three FLs initially graded by World Health Organization criteria (grade 1, 12; grade 2, 18; grade 3, 13) were reviewed and stained with CD3, CD20, Ki-67, CD30, CD68, PAX-5, and BCL-6. Retrospective review was performed for the average number of large cells, of large lymphoid cells, of large cells staining with CD3, CD20, BCL-6 (40 cases), and PAX-5, and of all cells staining with CD68, Ki-67, and CD30. RESULTS: By histologic review, 8 of 43 FLs had a significant grade change (4 cases upgraded and 4 cases downgraded). CD3 and CD30 stained only 0 to 3 large cells and 0 to 3 cells, respectively, in neoplastic follicles. CD68+ cells represented the large nonlymphoid cells. Increasing FL grades demonstrated increases in Ki-67+ cells. The original grade showed substantial agreement with CD20 and moderate agreement with PAX-5 and BCL-6. The original histologic grade agreed with immunohistochemical-based grade using 2 or more antibodies in 5 of 8 discordant cases (4 by CD20 or BCL-6 and PAX-5; 1 by CD20, PAX-5, and BCL-6). CONCLUSIONS: Interobserver variability of histologic FL grading may be significant; we showed low-end "substantial agreement." Immunohistochemical stains (ie, CD20, PAX-5, and BCL-6) may more reliably determine the number of large transformed cells in neoplastic follicles; Ki-67 staining correlates with higher FL grades. Immunohistochemical stains may be evaluated in clinical trials of FL patients to determine prognostic significance.

Bronchiolitis obliterans with organizing pneumonia after rituximab therapy for non-Hodgkin's lymphoma.

Rituximab is a chimeric, anti-CD20 monoclonal antibody initially approved for relapsed, refractory indolent B-cell non-Hodgkin's lymphoma (NHL), and is being applied in an increasing variety of clinical scenarios. Most adverse events are due to an infusion-related symptom complex, and severe pulmonary complications are rare. We describe a case of an NHL patient who received rituximab and developed symptomatic, biopsy-proven multinodular bronchiolitis obliterans with organizing pneumonia (BOOP). This is the first reported case of BOOP associated with single-agent rituximab, and along with two other patients we describe, as well as two prior reports of BOOP in NHL patients receiving rituximab-based combinations, strengthens the possibility of a causal relationship. Moreover, these findings suggest that the incidence of BOOP following rituximab therapy may be higher than has been previously appreciated. Physicians utilizing rituximab should be aware of this association given the difficulty of differentiating between presentations of BOOP and neoplastic pulmonary processes.

An immunohistochemical evaluation of c-kit (CD-117) expression in malignant melanoma, and results of imatinib mesylate (Gleevec) therapy in three patients.

In order to determine whether imatinib mesylate (Gleevec), a tyrosine kinase inhibitor that binds the CD-117 (c-kit) receptor, may be of value in the treatment of malignant melanoma, an immunohistochemical analysis of 40 cases of primary and metastatic melanoma was undertaken. Thirty-five of the 40 cases showed 1+ or stronger labelling for CD-117 (up to a maximum of 4+). Three patients with neoplasms showing 4+ staining were selected for imatinib therapy. None responded. c-kit (CD-117) expression in melanoma appears to be common; however, the value of imatinib therapy remains to be proven.

The faces of mast cell disease: bone marrow infiltrates in 3 patients with systemic mastocytosis.

The clinical spectrum of mast cell disease ranges from relatively innocuous and histologically subtle urticarial skin lesions to an aggressive and fatal leukemic form of mast cell proliferation. Not surprisingly, mast cell infiltrates may show significant microscopic heterogeneity, particularly in the bone marrow, the most common site of involvement in systemic mastocytosis (SM). Herein, 3 cases are presented to illustrate the clinical and morphologic heterogeneity of mast cell disease: the first patient, with long standing urticaria pigmentosa, developed anemia and thrombocytopenia; the second patient presented with a pathologic fracture; and the third patient was suspected to have refractory anemia. Upon bone marrow examination, all 3 patients showed mast cell infiltration with distinct morphologic features and all met the WHO criteria for aggressive systemic mastocytosis. Histochemical methods continue to play a role in the identification of mast cells, with some limitations depending on the degree of differentiation of the mast cells and tissue processing methods. Immunohistochemistry has contributed to the identification of mast cells. Coexpression of CD117 and CD25, as well as expression of the more specific immunohistochemical marker tryptase, is seen in systemic SM. The latter may also be employed as a serum marker in the diagnosis and follow-up of patients with SM. The mast cells, in the majority adults with SM, have somatic point mutations of KIT.

Kaposiform hemangioendothelioma associated with nonimmune fetal hydrops.

We describe the case of a 31-week fetus who died in utero with an invasive retroperitoneal kaposiform hemangioendothelioma. This rare vascular neoplasm usually presents as a localized violaceous skin lesion in infants and behaves in a benign fashion; however, kaposiform hemangioendothelioma may present as an invasive neoplasm of the chest or abdominal cavity, where it can lead to the Kasabach-Merritt syndrome, which consists of thrombocytopenia, consumptive coagulopathy, and microangiopathic anemia in association with a vascular anomaly. The case we describe is unique in that the tumor presented in utero and led to intrauterine nonimmune fetal hydrops. Kaposiform hemangioendothelioma has been described in utero; however, to our knowledge, intrauterine fetal death as a direct consequence has not been reported previously in the literature.