Incidence and clinical significance of aberrant T-cell marker expression on diffuse large B-cell lymphoma cells.

INTRODUCTION: Aberrant expression of T-cell markers is occasionally observed in B-cell lymphomas. We conducted a retrospective study to establish its incidence and to determine its relationship with clinical features of patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We reviewed DLBCL patients diagnosed between January 2002 and April 2009. Patients fulfilled the following criteria: (1) age >18 years, (2) HIV negative, (3) B-cell lymphoma confirmed by restricted expression of surface immunoglobulin light chains by flow cytometry (FCM). Aberrant T-cell marker expression (ATCME) was defined as positivity for CD2, CD3, CD4, CD7, and/or CD8 on DLBCL cells by FCM. Phenotyping was also performed by immunohistochemistry (IHC). Patients were grouped according to positive or negative ATCME and their clinical features including survival were compared. RESULTS: Of 150 patients, 11 (7.3%) showed ATCME; CD2 and CD7 were most often expressed. ATCME was less often detected and the signal was weaker using IHC. There were no statistically significant differences in clinical features between the two groups. CONCLUSIONS: FCM may be useful to detect ATCME in a small amount of lymphoma cells. The mechanism responsible for ATCME, and whether it contributes in any way to the pathogenesis of B-cell neoplastic transformation, requires clarification.

Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL.

Diffuse large B-cell lymphomas (DLBCL) express CD20. CD20 expression is described as negative, weak, or normal as determined by flow cytometry (FCM) and is an important target for the treatment of DLBCL. However, the impact of CD20 levels at onset of the disease on patient prognosis has not been fully elucidated. We analyzed 174 DLBCL cases newly diagnosed between January 1998 and April 2010. The relationship of the association between CD20 levels and patients' backgrounds and prognoses was analyzed using the Kaplan-Meier method and Cox proportional hazard regression. Of the 174 patients, three cases (1.7%) were defined as CD20 negative based on immunohistochemistry (IHC). Although the other 171 cases were positive by IHC, eight cases (4.7%) were defined as negative and 33 cases (19.3%) were defined as weak when analyzed by FCM. Of the 105 patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy, those who were CD20 negative (FCM) showed significantly inferior overall (hazard ratios (HR): 6.79, 95% CI: 1.32-34.96, p = 0.04) and progression-free survival (HR: 7.3, 95% CI: 1.49-35.8, p = 0.04) compared to patients who were CD20 normal. Our findings indicate that the CD20 level (FCM) at onset is an independent predictor of the prognosis of patients with DLBCL.

Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings.

PURPOSE: To compare the capability of diffusion-weighted (DW) and contrast material-enhanced magnetic resonance (MR) imaging to provide diagnostic information on residual breast cancers following neoadjuvant chemotherapy and to assess apparent diffusion coefficients (ADCs) of the carcinoma prior to neoadjuvant chemotherapy to determine if the method could help predict response to chemotherapy. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Three hundred ninety-eight patients underwent MR imaging of the breast, including DW MR (b values, 0 and 1500 sec/mm(2)) and contrast-enhanced MR imaging. Of these, the contralateral breast in 73 women was used as a control. Seventy-two patients with 73 lesions with malignant disease were treated by using neoadjuvant chemotherapy and were examined for residual disease following therapy. Three were excluded because of prolonged intervals between final MR imaging and surgery. Thus, 69 patients (70 lesions) with DW and contrast-enhanced MR imaging results were compared with postoperative histopathologic findings. The ADCs of the carcinoma prior to neoadjuvant chemotherapy were calculated for each patient, and those with complete response and residual disease were compared. RESULTS: The accuracy for depicting residual tumor was 96% for DW MR imaging, compared with an accuracy of 89% for contrast-enhanced MR imaging (P = .06). There was no significant difference in prechemotherapy ADCs between pathologic complete response cases and those with residual disease. CONCLUSION: DW MR imaging had at least as good of accuracy as did contrast-enhanced MR imaging for monitoring neoadjuvant chemotherapy. The ADCs prior to chemotherapy did not predict response to chemotherapy. The use of DW imaging to visualize residual breast cancer without the need for contrast medium could be advantageous in women with impaired renal function.

Diffusion-weighted imaging of mucinous carcinoma of the breast: evaluation of apparent diffusion coefficient and signal intensity in correlation with histologic findings.

OBJECTIVE: The purposes of this study were to compare the apparent diffusion coefficient (ADC) of mucinous carcinoma of the breast with that of other breast tumors and to analyze correlations between signal intensity on diffusion-weighted images and the histologic features of mucinous carcinoma. SUBJECTS AND METHODS: Two hundred seventy-six patients with 277 lesions, including 15 mucinous carcinomas (13 pure type, two mixed type), 204 other malignant tumors, and 58 benign lesions, were examined with 1.5-T MRI at b values of 0 and 1,500 s/mm(2). The correlations between cellularity and ADC, homogeneity of signal intensity on diffusion-weighted images, and histopathologic findings were analyzed. The difference was statistically significant (p < 0.05). RESULTS: The mean ADC of mucinous carcinoma (1.8 +/- 0.4 x 10(-3) mm(2)/s) was statistically higher than that of benign lesions (1.3+/- 0.3 x 10(-3) mm(2)/s) and other malignant tumors (0.9 +/- 0.2 x 10(-3) mm(2)/s) (p < 0.001). The ADC of pure type mucinous carcinoma (1.8 +/- 0.3 x 10(-3) mm(2)/s) was higher than that of mixed type mucinous carcinoma (1.2 +/- 0.2 x 10(-3) mm(2)/s) (p < 0.001) and other histologic types (p > 0.05). The correlation between mean cellularity and the ADC of mucinous carcinoma was significant (rho(s) = -0.754; p = 0.001). The homogeneity of signal intensity on diffusion-weighted images correlated with the homogeneity of histologic structures of mucinous carcinoma (p < 0.001; kappa = 0.826). CONCLUSION: Mucinous carcinoma can be clearly differentiated from other breast tumors on the basis of ADC. The low signal intensity of mucinous carcinoma on diffusion-weighted images appears to reflect the presence of mucin and low cellularity. High signal intensity on diffusion-weighted images may reflect the presence of fibrovascular bundles, increased cell density, or a combination of these features.

Splenic infarction after Epstein-Barr virus infection in a patient with hereditary spherocytosis.

We describe the first patient with hereditary spherocytosis (HS) known to have developed splenic infarction following infectious mononucleosis (IM). An 18-year-old Japanese man was referred to our hospital in November 2004 because of continuous fever and icterus. He had undergone cholecystectomy at the age of 14 years. On patient admission in November 2004, a physical examination showed marked hepatosplenomegaly, icterus, and jaundice. He had a white blood cell count of 14.9 x 10(9)/L with 9.5% atypical lymphocytes, a red blood cell count of 2.93 x 10(12)/L, and a hemoglobin concentration of 7.8 g/dL. Microspherocytes were observed in the patient's peripheral blood smear, and immunoglobulin M antibody to Epstein-Barr virus (EBV) viral capsid antigen was detected. The patient's diagnosis was HS with IM. On day 4 of admission, the patient complained of severe abdominal pain. Abdominal computed tomography scanning revealed findings of splenic infarction. Two months after the occurrence of splenic infarction, a splenectomy was performed. A pathohistologic examination of the resected spleen revealed no evidence of thrombosis or arterial occlusion. We assume that the cause of splenic infarction was insufficient blood flow to oxygenate the entire spleen during the acute enlargement of the spleen.

Basement membrane-like substance in cytologic diagnosis in clear cell adenocarcinoma of the minor salivary gland of the palate. A case report.

BACKGROUND: Clear cell adenocarcinoma (CCA) of the minor salivary gland accounts for < 1% of all tumors of the salivary gland. CASE: A 32-year-old woman with a history of papillary carcinoma of the thyroid 1 year earlier complained of pain on the left side of the neck. After a detailed examination, the patient underwent the resection of a tumor located at the palate. Imprint cytology of the tumor revealed cohesive tumor cells of uniform size containing an abundant clear cytoplasm and round nuclei with extra but fine granular chromatin and conspicuous nucleoli. A basement membrane-like substance (BMS) was stained in light green with Papanicolaou staining and was positive for laminin with immunohistochemical staining. Histopathologic analysis confirmed the trabecular or nest-like arrangement of the cells with the clear cytoplasm and BMS substance surrounded by tumor cells, which were positive for laminin and AE1 immunohistochemically. CONCLUSION: Although CCA of the palate is extremely rare, an accurate cytologic diagnosis can be made if the characteristic findings of CCA, including BMS, are imaged.

[Superficial bladder cancer with lung metastasis without local invasion: a case report].

A 66-year-old woman presented with a coin-size lesion in the right lung. Bronchoalveolar lavage cytology showed class V. Thoracoscopic partial pneumonectomy of right upper lobe was performed and pathologic finding was metastatic transitional cell carcinoma (TCC). She had a history of superficial bladder tumors which were treated with transurethral resection (TURBT). All pathologic findings demonstrated low grade superficial TCC. After the pneumonectomy, recurrent tumors were detected in the bladder after three months' follow up. Intravesical instillations and TURBT were performed and the pathologic finding showed superficial TCC. There have been no signs of recurrence during the six-year follow up. The case reported here is of superficial cancer with a metastatic lesion in the lung without local invasion in the urinary bladder.

[A case report: small cell carcinoma transformed from transitional cell carcinoma of the urinary bladder].

A 72-year-old man presented with gross hematuria. Cystoscopy showed a non-papillary tumor at the right side of the posterior wall. Transurethral resection of the bladder tumor (TURBT) was performed. Pathologic findings demonstrated superficial transitional cell carcinoma (TCC). However, recurrent tumors were detected at the same location after 69 months' follow up. TURBT was done for the biopsy and pathologic examination showed muscle-invasive TCC. After two courses of neoadjuvant chemotherapy (MVAC), we performed radical cystectomy with Hautmann's continent reservoir. Pathologic findings revealed small cell carcinoma without any TCC features. Immunohistochemical staining using chromogranin A and synaptophysin was positive in the latest TURBT and the radical cystectomy specimens. We report a case of primary small cell carcinoma transformed from TCC of the urinary bladder.

ADC mapping of benign and malignant breast tumors.

PURPOSE: The purpose of this study was to investigate the utility of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) value in differentiating benign and malignant breast lesions and evaluating the detection accuracy of the cancer extension. MATERIALS AND METHODS: We used DWI to obtain images of 191 benign and malignant lesions (24 benign, 167 malignant) before surgical excision. The ADC values of the benign and malignant lesions were compared, as were the values of noninvasive ductal carcinoma (NIDC) and invasive ductal carcinoma (IDC). We also evaluated the ADC map, which represents the distribution of ADC values, and compared it with the cancer extension. RESULTS: The mean ADC value of each type of lesion was as follows: malignant lesions, 1.22+/-0.31 x 10(-3) mm2/s; benign lesions, 1.67+/-0.54 x 10(-3) mm2/s; normal tissues, 2.09+/-0.27 x 10(-3) mm2/s. The mean ADC value of the malignant lesions was statistically lower than that of the benign lesions and normal breast tissues. The ADC value of IDC was statistically lower than that of NIDC. The sensitivity of the ADC value for malignant lesions with a threshold of less than 1.6 x 10(-3) mm2/s was 95% and the specificity was 46%. A full 75% of all malignant cases exhibited a near precise distribution of low ADC values on ADC maps to describe malignant lesions. The main causes of false negative and underestimation of cancer spread were susceptibility artifact because of bleeding and tumor structure. Major histologic types of false-positive lesions were intraductal papilloma and fibrocystic diseases. Fibrocystic diseases also resulted in overestimation of cancer extension. CONCLUSIONS: DWI has the potential in clinical appreciation to detect malignant breast tumors and support the evaluation of tumor extension. However, the benign proliferative change remains to be studied as it mimics the malignant phenomenon on the ADC map.

Genetics of synchronous uterine and ovarian endometrioid carcinoma: combined analyses of loss of heterozygosity, PTEN mutation, and microsatellite instability.

Synchronous development of carcinomas in the endometrium and ovaries is a fairly common phenomenon, but distinction of a single clonal tumor with metastasis from 2 independent primary tumors may present diagnostic problems. To determine clonality and the occurrence of progression, we microdissected multiple foci from 17 cases of synchronous endometrioid carcinomas and studied loss of heterozygosity (LOH), microsatellite instability (MI), and PTEN mutations. In 14 of the 17 cases, genetic alterations were either homogeneous or found in only some of the foci. LOH was detected for 10q (4 cases), 17p (2 cases), and 2p, 5q, 6q, 9p, 11q, 13q, and 16q (1 case each). Four cases had the MI phenotype with discordant MI patterns between both tumor sites, thus indicating a biclonal or triple clonal process. In 3 of 6 cases with PTEN mutations, identical mutations in both tumor sites indicated a single clonal neoplasm. Altogether, 14 synchronous tumors were genetically diagnosed as follows: single clonal tumor, characterized by concordant genetic alterations in both tumor sites, including identical LOH, identical PTEN mutations, and/or identical sporadic allelic instability patterns (4 cases); single clonal tumor with genetic progression, homogeneous LOH or identical PTEN mutations in both tumor sites and progressive LOH in ovarian metastatic foci (2 cases); and double (7 cases) or triple clonal tumors (1 case), determined by discordant PTEN mutations, heterogeneous LOH, and/or discordant MI patterns. Thus, 35% of synchronous tumors were monoclonal, 47% were polyclonal, and 18% were undetermined. The favorable prognosis of synchronous endometrioid carcinomas may be due to the occurrence of PTEN mutations in both independent and metastatic tumors, the MI-positive independent primary tumors, and the low frequency of LOH.

A Kaposi-like variant of splenic angiosarcoma lacking association with human herpesvirus 8.

We report the case of a Kaposi-like variant of splenic angiosarcoma in a 28-year-old woman. The tumor featured a Kaposi sarcoma-like spindle cell proliferation with slit formation and markedly dilated spongelike vascular channels filled with erythrocytes. Thirteen months following the initial splenectomy, metastatic lesions were found in the patient's liver and bone marrow. The proliferating cells were positive for factor VIII-associated antigen and CD34. The human herpesvirus 8 genome, which is regarded as a diagnostic feature of Kaposi sarcoma, was not detected by polymerase chain reaction analysis. Although the histologic findings were similar, this Kaposi-like variant of splenic angiosarcoma must be considered distinct from Kaposi sarcoma.

A case of malignant fibrous histiocytoma (MFH) in the skull bone presenting extensive permeative osteolysis.

Malignant fibrous histiocytoma (MFH) of the skull is rare. This case showed an extremely unusual growth pattern for MFH. The radiographs and magnetic resonance imaging (MRI) demonstrated an osteolytic growth pattern in the skull base and temporal bone, without forming a mass lesion. We considered the possibility of a malignant tumor with a myxoid component based on its growth pattern and MRI intensity. Pathological examination revealed dense proliferation of the neoplastic spindle cells with storiform pattern and focal myxoid or fibrotic areas. Only one other case of MFH with myxoid change of the skull bone has been documented in the English literature.

Laminin-5 immunohistochemical mapping for analysis of local extension in hypopharyngeal cancer: A preliminary report.

OBJECTIVE: Laminin-5 γ2 chain (LNγ2) plays an important role in cancer differentiation and migration. Using a novel immunohistochemical mapping technique to investigate whole mucosal strips of total laryngopharyngectomy specimens using iodine, H-E, and LNγ2 stainings, we investigated the locoregional behavior of hypopharyngeal cancer. METHODS: Surgical specimens from two patients with pyriform sinus cancer were investigated. Three percent iodine was applied to the tumor-bearing laryngopharynx during surgery and photographed. Stainabilities of H-E and LNγ2 on pathologic sections from all mucosal strips were scored and coordinated with the laryngopharyngeal photograph to illustrate the immunohistochemical map. RESULTS: In both patients, the main tumor of invasive squamous cell carcinoma was circumferentially surrounded by a superficial lesion characterized by high grade intraepithelial neoplasia that remained unstained by iodine. On LNγ2 immunohistochemical mapping, the main tumor was demonstrated by Score 2 staining and the superficial lesion by a stronger Score 3 staining. CONCLUSIONS: The finding of neoplastic cells at the periphery demonstrating a higher potential than the cancer cells at the tumor center is suggestive of impending progression from neoplasia to carcinoma. The current preliminary report suggested morphological evidence of intraepithelial infiltration and lateral invasion in hypopharyngeal cancer.

Pathophysiological evaluation of cerecyte coil embolization for experimental broad neck aneurysms.

Cerecyte second-generation coils feature inner surfaces coated with an absorbable polyglycolic acid (PGA) polymer. Their use is expected to accelerate aneurysm organization, but time course data are limited. The present experimental study was therefore conducted to clarify the processes by pathological examination. Methods. Two types of experimental aneurysms were initially generated in adult mongrel dogs, one bifurcation and another of lateral wall type. Long-term persistence of each was defined by follow-up angiography for more than 1 year. Embolization of the aneurysms was then performed using only cerecyte coils, and follow-up angiography was conducted after 2 and 4 weeks followed by pathological examination. Results. Organization of both types of broad neck aneurysm was apparent 4 weeks after embolization, which is earlier as compared with already reported data for bare coils.

Clinical significance of intraoperative surgical margin study in supracricoid laryngectomy.

OBJECTIVE: Supracricoid laryngectomy (SCL) is a reliable procedure for laryngeal preservation. However, due to the limited anatomy of the larynx, close surgical margins are often inevitable. Although the usefulness of intraoperative margin study on frozen section has been well documented in laryngeal surgery, the clinical significance of margin study in SCL has not been clarified. This study evaluated the evidence base supporting margin study in SCL. METHODS: Between 1997 and 2009, 61 patients underwent SCL. Margin study was conducted by histopathologically examining surrounding mucosal strips between the resected laryngeal specimen and the residual larynx using frozen sections. The findings were analyzed in terms of pT staging and prognoses. RESULTS: Among all patients, pathological report indicated all negative in 36, dysplasia in 18, and positive findings in seven patients. Positive results were exclusively identified at the ipsilateral posterior and inferior margins. The incidence of local recurrence and death due to disease was slightly higher in patients with positive reports. The margin study influenced the intraoperative decision to convert from SCL to total laryngectomy in one case. CONCLUSIONS: In reviewing the margin study of 61 SCL patients, 11% resulted in positive margin. All except one patient with positive margin attained negative finding with additional samplings. Decision making regarding the resection margin can be difficult in patients with pT3-pT4 stages and postradiation status. Because of the exclusive identification of positive margin at the ipsilateral posterior and inferior edges, the margin study is strongly recommended at these sites. The possibility of converting SCL to TL should be discussed preoperatively during the informed consent process. The margin study is an effective modality for ensuring the validity of SCL and is recommended for all SCL procedures.

Angiolymphoid hyperplasia with eosinophilia on penile skin in a 7-year-old child.

We report a case of a 7-year-old child who presented with a painless mass on his penis. He underwent removal of the mass, which was found to be an angiolymphoid hyperplasia with eosinophilia. Angiolymphoid hyperplasia with eosinophilia is an extremely rare tumor, especially in children's penis. In this situation, treatment of this tumor should be considered carefully, and there is a chance of spontaneous regression after volume reduction surgery.

Prevalence of topoisomerase I genetic mutations and UGT1A1 polymorphisms associated with irinotecan in individuals of Asian descent.

Topoisomerase I (TOP-I) mutations have been shown to be correlated to irinotecan resistance in vitro. However, the prevalence of TOP-I germline mutations has yet to be systematically elucidated. On the other hand, polymorphisms of UGT1A1 have been shown to be associated with CPT-11 toxicity in clinical situations. The primary aim of this study was to investigate the prevalence of mutations in the TOP-I exons associated with CPT-11 resistance, including untreated cancer tissue. A secondary aim was to confirm the less frequent UGT1A1*28 and more frequent UGT1A1*6 in individuals of Asian descent compared to Caucasians and individuals of African descent. The prevalence of 5 reported TOP-I mutations in exons was investigated in volunteers (n=236) using DNA sequencing of the PCR products. The prevalence of TOP-I mutations in untreated lung cancer tissues (n=16) was also investigated. Additionally, 3 UGT1A1 polymorphisms, UGT1A1*6, *27 and *28, were investigated in volunteers (n=126). There were no mutations of TOP-I in any of the 236 subjects or in the untreated lung tissues. Among 128 subjects, the distribution of homozygous polymorphisms of UGT1A1 was: UGT1A1*28 in 3 (2.4%) and UGT1A1*6 in 4 (3.2%) subjects, and co-occurrence of heterozygous polymorphisms for both UGT1A1*6 and UGT1A1*28 in 4 (3.2%) subjects, and for UGT1A1*27 and UGT1A1*28 in 1 subject (0.8%). The Hardy-Weinberg deviation test showed there was no significant deviation from the equilibrium, and the association analysis indicated no significant linkage between UGT1A1*6 and UGT1A1*28. In conclusion, TOP-I genetic mutations correlated to CPT-11 resistance were not detected in any of the subjects and untreated lung cancer tissues. Less frequent UGT1A1*28 and more frequent UGT1A1*6 were confirmed in East Asian individuals compared to Caucasians and individuals of African descent. Linkage disequilibrium was not detected between UGT1A1*6 and UGT1A1*28.

Primary central nervous system large B-cell lymphoma with prolific, mixed T-cell and macrophage infiltrates, mimicking multiple sclerosis.

Although tissue confirmation is essential for a diagnosis of primary central nervous system large B-cell lymphoma (PCNSBL), accurate assessment may still be difficult, even when tissue is obtained. We report a 59-year-old man, first diagnosed as multiple sclerosis by open biopsy at another institution, who was then correctly diagnosed as PCNSBL after stereotactic biopsy at our hospital. The initial biopsy showed heavy lymphoid and macrophage influx with visible demyelination. On rebiopsy, a diffuse infiltrate of small to medium-sized lymphocytes was prominent and largely stained as T cells (CD3) by immunohistochemistry. There was also an admixture of macrophages, but this time, relatively low numbers of large malignant cells were also identified. The latter stained as B cells (CD20), enabling a diagnosis of B-cell lymphoma, and the condition responded fully to high-dose methotrexate. It is thus possible for PCNSBL to be histologically misinterpreted as a result of ancillary inflammation, characterized here as a profusion of T cells and macrophages.

Expression of S100A2 and S100A4 predicts for disease progression and patient survival in bladder cancer.

OBJECTIVES: To determine the expression patterns and prognostic value of S100A2 and S100A4 in surgical specimens from radical cystectomy for transitional cell carcinoma of the urinary bladder. METHODS: Immunohistochemical staining for S100A2 and S100A4 was performed in 92 archived radical cystectomy and 38 normal specimens. The immunoreactivity of these proteins was stratified on a 0 to 6 scale and then correlated with the pathologic features and clinical outcome. RESULTS: S100A2 expression was significantly decreased in the bladder cancer specimens compared with the controls (P <0.0001), and S100A4 expression was significantly greater in the bladder cancer specimens (P = 0.03). The loss of expression of S100A2 and increased expression of S100A4 were associated with muscle invasion (P <0.05). These alterations in expression were also associated with a greater risk of disease progression and a decreased chance of cancer-specific survival at a median follow-up of 25.3 months (P <0.0001 for both). After adjusting for the effects of the pathologic findings, S100A4 expression remained a significant predictor of disease progression (P <0.0001) and cancer-specific survival (P <0.0001). CONCLUSIONS: S100A4 appeared to be an independent predictor for the treatment outcome in bladder cancer. The expression patterns of S100A2 and S100A4 correlated well with the pathologic stage, disease progression, and cancer-specific mortality. This finding could aid in identifying more biologically aggressive cancers and thus patients who might benefit from more intensive adjuvant therapy.

A case of pure red cell aplasia complicated with diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant: effectiveness of rituximab and implications for a common immunopathogenic role of B lymphocytes.

Diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant (DLBL-TH), is characterized by the presence of neoplastic B cells set in a background containing numerous non-neoplastic T lymphocytes and histiocytes. We report here the case of a patient with DLBL-TH who developed overt pure red cell aplasia (PRCA) following chemotherapy and autologous peripheral blood stem cell transplantation. Posttransplantation bone marrow biopsies revealed the absence of erythroid precursors associated with lymphoid aggregates composed of B cells mixed with numerous T cells and histiocytes. Administration of rituximab has led to complete recovery of erythropoiesis, which was associated not only with B cell depletion but also with a marked reduction in bone marrow T cells and histiocytes. These observations strongly suggest the particular pathogenetic role of the patient's B cells in inducing PRCA and recruiting T cells and histiocytes in situ.