Is lymphoplasmacytic lymphoma/immunocytoma a distinct entity? A clinicopathologic study of 20 cases.

Lymphoplasmacytic lymphoma/immunocytoma (LLI) was defined initially as a small B-cell lymphoma with plasmacytoid or plasmacytic features. Because other types of small B-cell lymphoma, particularly marginal zone B-cell lymphoma may exhibit plasmacytic differentiation, the revised European-American lymphoma classification and World Health Organization has defined LLI more narrowly to exclude other small B-cell lymphomas. The goal of this study was to reevaluate LLI as a clinicopathologic entity. Twenty cases were selected from 43 previously diagnosed as "small lymphocytic lymphoma, plasmacytoid" or "immunocytoma" from 1985 to 1998. Cases fulfilling the criteria for B-cell small lymphocytic lymphoma, follicular lymphoma, marginal zone B-cell lymphoma, or other types of B-cell lymphoma were excluded. The histopathology and immunoreactivity for CD20, CD79a, CD3, CD43, CD23, CD5, kappa, lambda, and immunoglobulins (Ig's) M, G, and A were reviewed, in addition to available clinical findings. There were 13 men and seven women, with a mean age of 69 years. Five patients had documented Waldenström's macroglobulinemia (WM). Three architectural patterns were observed. Pattern A (seven of 20) showed open sinuses, small follicles, and hemosiderosis; pattern B (four of 20) showed hyperplastic follicles; and pattern C (nine of 20) showed diffuse effacement. Epithelioid histiocytes were prominent in patterns B and C but absent in A. Cytologically, six of 20 were polymorphous with 10% to 40% transformed cells; 14 of 20 were lymphoplasmacytic. Five cases showed minor foci of monocytoid B cells. One case showed a composite histology of LLI and small lymphocytic lymphoma. Amyloid was present in two cases. All cases were CD20 and/or CD79a immunoreactive, with two of 20 positive for CD43. Twelve cases were kappa monoclonal and eight cases were lambda monoclonal. Twelve of 17 cases that could be evaluated were positive for IgM and five were positive for IgG. All cases were negative for CD5 and CD23 with the exception of the one case with a composite histology. Eleven of 20 patients with available follow-up died of disease (median, 48 months), and eight of 20 are alive with disease at a follow-up of 6 months to 2 years. LLI does appear to represent a distinct clinicopathologic entity even though it shows morphologic heterogeneity and overlapping features with marginal zone B-cell lymphoma and small lymphocytic lymphoma. Recognition of LLI is important because the overall prognosis may be worse than for other types of small B-cell lymphomas.

Interdigitating dendritic cell sarcoma. A report of four cases and review of the literature.

To better define the clinical and pathologic features of interdigitating dendritic cell sarcoma (IDCS), we report 4 cases, including the first reported in the tonsil. There were 2 male and 2 female patients (mean age, 70 years). Sites of tumor included 1 case each in the right cervical lymph node, left axillary lymph node, right tonsil, and right inguinal lymph node. Histologically, all showed diffuse effacement of the lymphoid tissue by pleomorphic round to spindled cells with convoluted nuclei and abundant eosinophilic cytoplasm. All were immunoreactive for S-100, CD68, lysozyme, and vimentin. CD45 was positive in 3 cases and CD1a in 1 case. Fascin was positive in 3 cases. Other immunostains, including CD3, CD20, CD21, CD30, actin, cytokeratin, and HMB-45, were negative. Ultrastructurally, the tumor cells were elongated and showed indented nuclei, variable numbers of lysosomes, and interdigitating cytoplasmic processes. Follow-up was available for all cases. One patient died of widespread disease 2 months after diagnosis. One was alive with metastatic lung disease at 12 months. Two patients were disease free at 5 and 9 months.

Rosai-Dorfman disease isolated to the central nervous system: a report of 11 cases.

Sinus histocytosis with massive lymphadenopathy, also known as Rosai-Dorfman Disease (RDD), is an idiopathic histiocytic proliferation affecting lymph nodes. Although extranodal involvement has been reported in diverse sites, central nervous system (CNS) manifestation, particularly in the absence of nodal disease is uncommon. We report 11 cases of RDD primary to the CNS without evidence of other sites of involvement. The cases included 7 males and 4 females ranging in age from 22 to 63 years (mean: 41 y). The patients presented with headaches, seizures, numbness, or paraplegia. Eight cases involved the cranial cavity and three cases, the spinal canal. Lesions were most often extra-axial and dura based. Only one presented in the CNS parenchyma. Histologically, the lesions consisted of variable numbers of pale-staining histocytes with emperipolesis often overshadowed by extensive lymphoplasmacytic infiltrates and fibrosis in the background. Special stains for organisms were negative. By immunohistochemical analysis, the characteristic histiocytes were positive for S100 protein and CD68 and negative for CD1a. Treatment consisted of surgical biopsy or excision. Follow-up, available for 10 cases with intervals ranging from 5 days to 42 months (mean: 15 mo), disclosed one patient dying of operative complications 5 days after biopsy and nine patients with no evidence of disease progression RDD should be considered in the differential diagnosis of inflammatory lesions of the CNS. Our study suggests that this entity may have been misdiagnosed in the past as plasma cell granuloma or inflammatory pseudotumor.

Splenic inflammatory myofibroblastic tumor (inflammatory pseudotumor): a clinicopathologic and immunophenotypic study of 12 cases.

CONTEXT: Inflammatory pseudotumor is an uncommon and enigmatic lesion. The spindle cells found in this tumor have features of myofibroblasts. Because of the indefinite relationship of these lesions with inflammatory fibrosarcoma and their indefinite biologic behavior, inflammatory pseudotumor is currently classified as inflammatory myofibroblastic tumor (IMT). To date, only case reports or small series have been published on these tumors, which are primary in the spleen. DESIGN: In this study, we describe the clinical, morphologic, and immunophenotypic findings of 12 cases of splenic IMT and examine their relationship to Epstein-Barr virus (EBV). RESULTS: The patients included 8 women and 3 men, ranging from 19 to 77 years of age (mean, 53 years; median, 60 years). Demographic data were unavailable for 1 patient. Patients generally presented with abdominal pain (n = 5) and fever (n = 4). Associated lesions included renal cell carcinoma (n = 2), colonic adenocarcinoma (n = 1), and cholecystitis (n = 1). All tumors were composed of a bland spindle cell proliferation in association with a variable mixed inflammatory component. There were 2 growth patterns, namely, a cellular spindle cell pattern and a hypocellular fibrous pattern. An immunohistochemical panel confirmed the myofibroblastic nature of the spindle cells. The spindle cells of 2 cases were immunoreactive for EBV latent membrane protein 1, whereas 6 of 10 cases were positive for EBV-encoded RNA using in situ hybridization. Follow-up was available for 8 patients; 6 were alive with no evidence of recurrence and 2 were dead of other causes. CONCLUSION: Splenic IMTs are uncommon lesions that can be distinguished from other conditions using a combination of clinical, histologic, and immunophenotypic findings. Epstein-Barr virus may play a role in the pathogenesis of splenic IMT, and there may be an association of splenic IMT with concomitant disease or malignancy. Most splenic IMTs have an excellent long-term prognosis.

Pulmonary pathology of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis that may present with pulmonary symptoms. The condition seems to be nonfamilial and typically affects middle-aged adults. Radiographic and pathologic changes in the long bones are diagnostic, but patients often present with extraskeletal manifestations. Advanced pulmonary lesions are associated with extensive fibrosis that may lead to cardiorespiratory failure. The clinical, radiologic, and pathologic features of six patients with ECD with lung involvement are presented. The patients were three men and three women (mean age, 57). Five presented with progressive dyspnea, and one presented with diabetes insipidus. Open-lung biopsies showed histiocytic infiltrates in a lymphangitic pattern with associated fibrosis and lymphoplasmacytic inflammatory infiltrates. The histiocytes did not stain with periodic acid-Schiff. Immunoperoxidase studies performed on specimens from five of six patients showed that the histiocytes were positive for CD68 and Factor XIIIa and negative for CD1a. Specimens from two patients exhibited immunoreactivity for S-100 protein. Electron microscopy studies performed on specimens from two patients showed phagocytic lysosomes but no Birbeck granules. Clinical follow-up of up to 16 years was available. At the end of that time, five patients were dead of complications related to their disease; one patient remains alive 4 years after diagnosis but with severe respiratory compromise. ECD is a rare non-Langerhans' cell histiocytosis that may present as interstitial lung disease and resemble other pulmonary conditions, particularly usual interstitial pneumonitis and pulmonary Langerhans' cell histiocytosis. Recognition of this entity will allow better assessment of its true incidence, therapeutic options, and prognosis.

Anaplastic large cell lymphoma (CD 30+), T-phenotype, in the heart of an HIV-positive man.

Non-Hodgkin's lymphomas described in patients with HIV-infection are most often high-grade B-cell lymphomas. Anaplastic large cell lymphoma (CD 30+) has been described in a minority of immunocompromised patients. Although sporadic reports of T-cell lymphomas associated with HIV infection are found in the literature, they have not been described to occur in the myocardium. We present a case of anaplastic large cell lymphoma (CD 30+), T-phenotype involving the heart in a 42-year-old HIV-positive patient.

Primary anaplastic large cell lymphoma of the lung: a clinicopathologic study of five patients.

Primary anaplastic large-cell lymphoma is a rare malignancy in the lung. Anaplastic large-cell lymphoma characteristically involves the lymph nodes or skin, with few reports from other sites. We studied the clinical and pathologic features of five cases of anaplastic large-cell lymphoma limited to the lungs. The patients were three women and two men aged 27 to 66 years (mean, 44.6 y) The tumors ranged in size from 1.1 to 5 cm. All patients were CD 30 (Ki-1) positive and CD 15 (LeuM-1) negative. Epithelial membrane antigen immunoreactivity was seen in two patients. Epstein-Barr virus was not detected by immunohistochemistry (four patients tested) or by polymerase chain reaction studies (three patients tested). The immunophenotypes were T cell (n = 3) and null (n = 2). Gene rearrangement studies supported the immunophenotypic findings. One patient who had underlying HIV infection died of infectious complications. One patient died at 6 months. Two patients developed recurrent disease and are alive after 42 and 51 months of follow-up. The remaining patient is alive at 8 years of follow-up without evidence of disease. ALCL can mimic metastatic or primary carcinoma and should be considered in the differential diagnosis of large cell neoplasms of the lung.

Expression of CD44 (HCAM) in small lymphocytic and mantle cell lymphoma.

Small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL) are small B-cell lymphomas that share many morphological and immunophenotypic features, both expressing the T-cell antigen CD5. Because of this, there is speculation that these two lymphomas may have a common origin, both arising from the mantle zone of the lymph node. CD44 (HCAM), a glycoprotein "homing receptor," has been reported as a marker of small B-cell lymphomas for determining behavior as well as the nodal cell of origin. Intensity of CD44 expression also has been correlated with dissemination of lymphoma. We studied 50 cases with classic features of SLL (30 cases) or MCL (20 cases). Immunophenotypic analysis was performed on paraffin sections. All cases of MCL and SLL were CD20 positive; CD5 was expressed in 19 of 25 (76%) SLL and 11 of 15 (73%) MCL. Cyclin D1 was expressed in 11 of 17 (76%) MCL and no cases of SLL. CD43 coexpression was seen in 27 of 29 (93%) SLL and 17 of 19 (89%) MCL. CD23 was positive in 25 of 28 (89%) SLL and 2 of 20 (10%) MCL. Bcl-2 was positive in 18 of 22 (82%) SLL and 15 of 16 (94%) MCL. CD44 was positive with moderate to strong intensity in 11 of 30 SLL and 15 of 20 MCL. Peripheral blood involvement did not correlate with CD44 immunoreactivity. MCL tended to have intense CD44 immunoreactivity, whereas SLL tended to show weaker CD44 intensity. This trend in the intensity of CD44 in MCL suggests that CD44 may be helpful in distinguishing SLL from MCL and possibly elucidating the origin of these CD5-positive B-cell neoplasms.

Reticulum cell neoplasms of lymph nodes: a clinicopathologic study of 11 cases with recognition of a new subtype derived from fibroblastic reticular cells.

Lymph nodes contain nonlymphoid accessory cells including follicular dendritic cells (FDCs), interdigitating dendritic cells (IDCs) and fibroblastic reticular cells (FBRCs). Neoplasms derived from FDCs are uncommon, and those of IDC origin are even more rare. We report the clinicopathologic features of 11 reticulum cell neoplasms, including 2 of FBRC origin. There were seven male patients and four female patients ranging in age from 13 to 73 years. All cases involved lymph nodes (cervical or supraclavicular-6 cases), (abdominal--2 cases), epitrochlear (1 case); two had more than one site of involvement (cervical lymph node and mediastinum--1 case, cervical and abdominal lymph nodes--1 case). One case of FDC tumor had concomitant Castleman's disease, plasma cell variant. Each neoplasm showed similar histology with oval-to-spindle-shaped cells in a storiform or fascicular pattern. Based on immunophenotypic findings, the neoplasms were classified as FDC (five cases), IDC (two cases), FBRC (three cases), and reticulum cell neoplasm, not otherwise specified (one case). The FDC tumors showed immunoreactivity for CD21 or CD35, vimentin, and CD68. The IDC tumors showed strong positivity for S-100 protein and variable positivity for CD68 and CD1a. The cases derived from FBRCs were positive for vimentin, desmin, and smooth-muscle actin. The neoplasm classified as reticulum cell neoplasm, not otherwise specified had similar morphologic features but showed only equivocal positivity for CD68 and vimentin. Follow-up was available for 9 of 11 (82%) cases with a mean of 3.5 years. Four of five patients with FDC tumors were alive with disease when last seen; the fifth is alive and well with no evidence of disease at 4-year follow-up. One patient with IDC tumor had a recurrence in a different nodal site. Two patients with FBRC tumor were disease free at follow-up of 2 years and 8 years, respectively. The patient with reticulum cell neoplasm, not otherwise specified, was alive and disease free 8 years after diagnosis.

Loss of tumor suppressor gene expression in high-grade but not low-grade non-Hodgkin's lymphomas.

The products of the MTS1/CDKN2 and retinoblastoma (RB) tumor suppressor genes, p16 and pRB, act as agonists in controlling the late G1 cell cycle checkpoint. Inactivation of either gene occurs in a wide range of human malignant neoplasms. Data on the expression of both genes in the same set of malignant lymphoid neoplasms are scarce. We studied the p16/pRB pathway in low-grade and high-grade non-Hodgkin's lymphomas, using immunohistochemical techniques. Paraffin sections of 9 reactive lymph nodes and 43 low-grade and 60 high-grade malignant lymphomas were reacted with antibodies against pRB and p16. All benign lymph nodes showed a normal pattern of RB and MTS1/CDKN2 expression. Of 101 evaluable lymphomas, only a single high-grade tumor displayed loss of RB reactivity. Loss of p16 was identified in 14 of 55 evaluable high-grade lymphomas but not in any of the low-grade lesions. All but 3 of the RB- and p16-negative cases were diffuse large cell lymphomas, for an abnormality rate of 55% in this category. While loss of RB function was a rare event in human lymphomagenesis, p16 was absent in some 25% of high-grade non-Hodgkin's lymphomas; diffuse large cell lymphomas were the primary target of tumor suppressor gene inactivation.

Waldenström's macroglobulinemia: a clinicopathologic study of 22 cases.

BACKGROUND: Waldenström's macroglobulinemia (WM) is a rare immunoproliferative disorder, the clinical course of which varies. In related B-cell neoplasms, such as multiple myeloma and chronic lymphocytic leukemia, the histologic features of bone marrow are considered to be of prognostic relevance. METHODS: To assess the prognostic features of WM, the authors reviewed the clinical and pathologic features of 22 patients. Bone marrow aspirates and core biopsies were available for each case. Immunostains for a panel of hematopoietic markers as well as p53 and proliferating cell nuclear antigen (PCNA) were performed. RESULTS: There were 14 males and 8 females, with a mean age of 60 years. At presentation, two histologic subtypes, lymphoplasmacytoid (73%) and lymphoplasmacytic (27%), were observed. Four patterns of bone marrow infiltration were delineated: diffuse (45%), nodular-interstitial (22%), mixed paratrabecular-nodular (20%), and paratrabecular (13%). In 11 patients, the infiltrate occupied greater than 70% of the bone marrow; in 8 patients, 30-70%; and in 3 patients, less than 30%. PCNA reactivity was observed in 58% of cases and p53 reactivity in 21%. Ten patients died of disease with an average survival of 84 months. The remaining 12 patients were alive with disease at last follow-up. The pretreatment parameters that were correlated with shorter survival were hemoglobin, white blood cell count, platelet count, splenomegaly, lymphadenopathy, and serum immunoglobulin M level. CONCLUSIONS: The findings of this study suggest that some pretreatment parameters, such as cytopenia, serum immunoglobulin M level, splenomegaly, and lymphadenopathy, correlate with poor prognosis for patients with WM. In contrast, histologic features and expression of p53 and PCNA did not correlate significantly with survival.

Childhood Hodgkin's disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus.

Hodgkin's disease (HD) typically has a bimodal age distribution and is less common than non-Hodgkin's lymphoma in the pediatric age group, especially in very young children. Recent reports described a high prevalence of Epstein-Barr virus (EBV) in HD from developing countries in both adult and pediatric populations. In this series, we studied with immunohistochemical analysis 44 cases of pediatric HD from the United States to investigate the association with EBV in developed countries and to determine which subtypes occur in this group. The 44 cases (40 boys, 4 girls; male-to-female ratio, 10:1) were categorized as nodular lymphocyte predominance in 16 (36.4%) of 44; nodular sclerosis in 13 (29.5%); and mixed cellularity in 4 (9.1%). Eleven of the cases were difficult to subclassify by the usual morphologic and immunophenotypic criteria. Of these, eight (18.1%) were designated interfollicular HD, and three were classified as HD "not otherwise specified." EBV LMP was positive in 38.6% of cases: 5 (38.5%) of the 13 with nodular sclerosis; 3 (75%) of the 4 with mixed cellularity; 1 (6.0%) of the 16 with nodular lymphocyte predominance; 7 (87.5%) of the 8 with interfollicular HD; and 1 (33.3%) of the 3 with HD "not otherwise specified." There was a strong association between the age of the patient and EBV expression. In children 4 years or younger, all of the 3 cases were LMP positive; in the 5- to 9-year-old age group, 8 (61.5%) of 13 were LMP positive; and in the 10- to 15-year-old group, only 21.4% were positive. Our results confirm the male predominance in pediatric HD and show an association with EBV, especially in the youngest patients and with the mixed cellularity and interfollicular subtypes. Most, but not all, cases of pediatric HD can be subclassified by traditional criteria.

Necrotizing arteritis in uncorrected tetralogy of Fallot with pulmonary artery.

A 10-year-old girl with uncorrected tetralogy of Fallot with pulmonary atresia presented with fevers of unknown origin and left lung infiltrates. At autopsy, necrotizing vascular changes resembling those of severe pulmonary hypertension (grade VI in the Health-Edwards classification) were confined to the left lung. Pulmonary blood flow and pressure were greater in the left lung and were provided by an enlarged collateral artery arising directly from the descending thoracic aorta. To our knowledge, this is the first report of necrotizing arteritis of the pulmonary arteries in uncorrected tetralogy of Fallot with pulmonary atresia.