[Peripheral Pulmonary Artery Aneurysm with Internal Thoracic Artery-Pulmonary Artery Shunt].

An 82-year-old woman with past history of pulmonary nontuberculous mycobacterial infection complained of hemoptysis and was pointed out the strongly stained nodule in the middle lobe of the right lung on chest enhanced computed tomography (CT), which was suggested to be peripheral pulmonary artery aneurysm. Angiography of the right internal thoracic artery (RITA) revealed the peripheral pulmonary artery aneurysm with the shunt from the branch of the RITA, which was considered to be the cause of hemoptysis. Transcatheter arterial embolization was performed for the branch of the RITA 2 times, however, the hemoptysis recurred again after 5 months. Therefore, after the third embolization for the RITA, the right middle lobectomy with amputation of the shunt vessel was performed. The patient has been well without hemoptysis for one year and 6 months after the surgery.

Postmortem evaluation of neuromuscular damages more extensive than the surgical intervention area after iliac crest bone graft.

Several complications may occur following iliac bone grafting, one of the common sites for autologous bone harvesting. Of these, it is difficult to localize the damage in neurological complications due to the presence of several nerves in a similar distribution area with variations among individuals. To minimize these complications, conventional clinical anatomical studies using normal human cadavers have estimated the theoretical neurological damage area corresponding to the surgical intervention area. We report a case of neuromuscular damage in a 93-year-old woman who had an iliac crest defect after a bone graft, based on the virtual and physical dissections with histological confirmations.In this study, the patient was confirmed to have severe neuromuscular complications with major complications including a hernia protruding through the iliac defect. One of the two ilioinguinal nerves was extracted with the hernia sac through the iliac defect, and its distal part was completely damaged. The iliohypogastric nerve, which was far from the defect foramen, also showed remarkable fibrosis and demyelination, affected by the degeneration of the transversus abdominis muscles.The present anatomical findings show that the area of eventual neuromuscular damage should be estimated to larger than the conventionally predicted area of direct nerve damage, which is usually concomitant with the surgical intervention area.

Ultrastructural changes in the choriocapillaris of N-methyl-N-nitrosourea-induced retinal degeneration in C57BL/6 mice.

N-methyl-N-nitrosourea (MNU) is known to cause apoptosis of photoreceptor cells and changes in retinal pigment epithelium (RPE). However, the changes in choriocapillaris, which nourishes photoreceptor cells by diffusing tissue fluid through RPE, have not been reported in detail. Therefore, we studied the ultrastructural transformation in and around the choriocapillaris to characterize the interdependence between choriocapillaris and surrounding tissue components in a mouse model. Seven-week-old male C57BL/6 mice were given a single intraperitoneal injection of MNU (60 mg/kg of body weight). Perfusion-fixed eyeballs were examined chronologically using immunohistochemistry and electron microscopy until the photoreceptor cells were lost. Sequential ultrastructural changes were observed in photoreceptor cells, RPE, Bruch's membrane, choriocapillaris, and choroidal melanocytes after an MNU injection. The lumens of the choriocapillaris narrowed following dilation, and the vascular endothelium showed structural alterations. When the photoreceptor cells were completely lost, the choriocapillaris appeared to be in a recovery process. Our results suggest that transport abnormality through Bruch's membrane and structural changes in the choroid might have influenced the morphology of choriocapillaris. The thin wall of the choriocapillaris appears to be the cause of the vulnerability with its altered morphology.

Foxc2 influences alveolar epithelial cell differentiation during lung development.

FOXC2, a forkhead transcriptional factor, is a candidate gene for congenital heart diseases and lymphedema-distichiasis syndrome and yellow nail syndrome; however, there are no reports on Foxc2 and the development of the lung. We have identified lung abnormalities in Foxc2-knockout embryos during investigation of cardiac development. The aim of this study was to clarify the morphological characteristics during lung development using ICR-Foxc2 knockout lungs. Mutant fetuses at embryonic days 10.5-18.5 were obtained from mating of Foxc2+/- mice and then analyzed. Notably, Foxc2-knockout lungs appeared parenchymatous and much smaller than those of the wild-type littermates. In the Foxc2 knockout lungs, the capillary beds remained distant from the alveolar epithelium until the late stages, the number of type2 alveolar cells per alveolar progenitor cell was lower and the type1 alveolar cells were thicker in Foxc2 knockout mice. In contrast, Foxc2 expression was only detected in the mesenchyme of the lung buds at E10.5, and it disappeared at E11.5 in Foxc2-LacZ knockin mice. Furthermore, the expression of Lef1 was significantly inhibited in E11.5 lungs. All of these results suggest that the abnormalities in Foxc2 knockout mice may involve maldifferentiation of alveolar epithelial cells and capillary vessel endothelial-alveolar epithelial approach as well as lymph vessel malformation. This is the first report about relationship between Foxc2 and lung development. This animal model might provide an important clue for elucidating the mechanism of lung development and the cause of respiratory diseases.

Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing tumor angiogenesis.

BACKGROUND: Vasohibin-2 (VASH2) has been identified as an endogenous and vascular endothelial growth factor (VEGF)-independent angiogenic factor that is highly expressed in tumor cells. In the present study, we aimed to determine whether pre-existing vascular changes can be used to predict tumor transformation as benign or malignant. We sought to characterize microvascular changes and tumor development in the intestinal tract of ApcMin/+ mice and ApcMin/+/Vash2-/- mice. METHODS: ApcMin/+ mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, a phenomenon termed the adenoma-carcinoma sequence. ApcMin/+ mice were mated with Vash2-/- mice with a mixed C57BL/6 background and the resulting pups were screened for the Min mutation and for the Vash2-/- gene by PCR. Intestinal tumors from ApcMin/+ mice and ApcMin/+/Vash2-/- mice were removed and either frozen or epon-embedded for subsequent analyses. For 3-dimensional imaging using confocal laser-scanning microscopy and transmission electron microscopy, cryosections were made, and immunofluorescent staining for various markers was performed. RESULTS: We found that structural abnormalities in tumor vessels from benign tumors resembled those in malignant tumors. In addition, a novel angiogenic factor, vasohibin-2 (VASH2) protein, was detected around tumor blood vessels in late-stage adenomas and adenocarcinomas, but was absent from early-stage adenomas in ApcMin/+ mice. Tumors used to examine endogenous VASH2 (derived from CMT93 colon carcinomas) were less vascularized in Vash2-/- mice and were more regular than those seen in wild-type (WT) mice. In addition, tumors in Vash2-/- mice were smaller than those in WT mice. Furthermore, cross-breeding of mice homozygous for a deletion of Vash2 with mice heterozygous for the APC mutation resulted in animals that showed a significant decrease in the number of polyps in the small intestine. CONCLUSION: We propose that VASH2 may modulate the onset of tumors in the gastrointestinal tract by regulating tumor angiogenesis.

Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats.

A single intravitreal injection of erythropoietin (EPO) (50 ng/eye) or phosphate-buffered saline was administered to 5-week-old Sprague-Dawley rats at the onset of diabetes mellitus (DM) to determine and evaluate the protective effect of EPO on retinal microvessels. DM was induced by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Morphological changes in microvessels in flat retinal preparations were evaluated during the subsequent 4 weeks by three-dimensional imaging of all blood vessels stained with fluorescein isothiocyanate-conjugated tomato lectin, following immunofluorescence techniques. No marked differences were observed in the shape or density of retinal vessels and the number of retinal capillary branches of the four groups [control, EPO, DM, and DM/EPO] up to 4 weeks after STZ administration. We also observed unique type IV collagen-positive filamentous structures that lacked both cellular elements and blood circulation (lectin-/type IV+ acellular strands), suggesting regressed vessel remnants. The lectin-/type IV+ acellular strands were detected soon after the onset of DM in the diabetic rats, and the number of these structures increased in the DM group (P < 0.01). A single intravitreal injection of EPO caused a significant reduction in the number of lectin-/type IV+ acellular strands to levels observed in the control group. However, the lectin-/type IV+ acellular strands were observed in the central area of the retina near the optic disc in all four groups. Intravitreal injection of EPO resulted in downregulation of the EPO receptor, vascular endothelial growth factor (VEGF), and VEGF receptor at 4 weeks. We conclude that EPO may play a primary role against the progression of diabetic retinopathy by reducing blood vessel degeneration at a very early disease stage.

A glioblastoma arising from the attached region where a meningioma had been totally removed.

The co-occurrence of different histological tumors in the nervous system is rare and is mainly associated with phakomatoses or radiation exposure. A 72-year-old man underwent surgery for a frontal convexity meningioma. Four years after the surgery, a new lesion was detected in the attached region where the meningioma had been removed. The second tumor exhibited a high degree of cellularity, atypical mitosis, pseudo-palisading and microvascular proliferation, and was immunohistologically positive for GFAP and was diagnosed as a glioblastoma. Wild-type isocitrate dehydrogenase 1 was found in the second specimen. A genetic analysis using comparative genomic hybridization showed a DNA copy number loss on 1p35, 9pter-21, 10, 11q23, 13q, 14q, 20q, 22q and a gain on 7 in the second specimen. Although the mechanism responsible for the consecutive occurrence of meningioma and glioblastoma has not been elucidated, five hypotheses are feasible: (i) the lesions occurred incidentally; (ii) a low-grade astrocytoma present at the time of the first operation transformed into a high-grade glioma during the next 4 years; (iii) radiation received during the endovascular treatment induced glioblastoma; (iv) a brain scar created at the time of the first operation for meningioma led to the occurrence of a glioblastoma; and (v) the previous meningioma affected the surrounding glial cells, causing neoplastic transformation.

Diffusion magnetic resonance imaging for enhanced visualization of malignant cerebral tumors and abscesses.

BACKGROUND: Several malignant tumors and brain abscesses have similar magnetic resonance imaging (MRI) findings. Because the prognosis and treatment strategies differ among these disorders, accurate preoperative diagnosis is very significant. Recently, diffusion-weighted imaging (DWI) and calculation of apparent diffusion coefficients (ADCs) have been reported to be useful to differentiate between the two disorders. MATERIALS AND METHODS: MRI and DWI were performed in 37 patients: 13 with glioblastomas, 14 with metastatic tumors, 7 with malignant lymphomas, and 3 with brain abscesses. The minimum ADC value (ADC min ) and mean ADC value (ADC mean ) were taken into consideration. RESULTS: Statistically significant differences were found in the enhanced lesions for ADC min and ADC mean between metastatic tumors and malignant lymphomas. The receiver operating characteristic analyses revealed no statistically significant differences among them. There were statistically significant differences in ADC mean in the cores of cystic lesions between brain abscesses and metastatic tumors or glioblastomas. CONCLUSIONS: Our results suggest that evaluation using ADC values may facilitate differentiating metastatic tumors from malignant lymphomas, and also metastatic tumors or glioblastomas from brain abscesses.

Community-acquired pneumonia distinguished from influenza infection based on clinical signs and symptoms during a novel (swine) influenza A/H1N1 pandemic.

AIMS: The numbers of patients with influenza-like illnesses increase during influenza outbreaks. A study was undertaken to distinguish community-acquired pneumonia (CAP) from influenza based on clinical signs and symptoms. METHODS: This retrospective study investigated patients with positive results in the rapid influenza antigen test and those diagnosed with CAP during an influenza A/H1N1 pandemic. Significant factors for predicting risk for CAP within 48 hrs from onset and at diagnosis were selected by multiple regression analysis. RESULTS: Within 48 hrs of onset and at diagnosis, age and coarse crackles significantly increased the risk of CAP whereas sick contact, sore throat, and rhinorrhoea significantly decreased the risk of CAP. Duration of illness, sputum, dyspnoea, chest pain, and coarse crackles also significantly increased the risk of CAP at diagnosis. CONCLUSIONS: CAP differed somewhat from influenza even within 48 hrs of onset and the differences became even more evident thereafter.

Epstein-Barr virus-related atypical lymphoproliferative disorders in Waldeyer's ring: a clinicopathological study of 9 cases.

BACKGROUND AND STUDY AIM: Because of the small biopsy specimens in the Waldeyer's ring (WR) the differential diagnosis between Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) and malignant lymphoma is occasionally difficult. We report here clinicopathological, immunohistochemical and genotypic findings of 9 cases of EBV-associated LPDs in WR. PATIENTS AND METHODS: Using formalin-fixed paraffin-embedded sections, histological analyses, immunohistochemistry, in situ hybridization and polymerase chain reaction were performed. RESULTS: Clinically, all 9 cases showed more than one atypical clinical finding of infectious mononucleosis including absence of systemic symptoms, absence of atypical lymphocytosis and age over 30 years. Histologically, 3 types were delineated: (1) Hodgkin lymphoma-like (n = 1), (2) T cell/histiocyte-rich large B cell lymphoma-like (n = 4), and (3) marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT)-like (n = 4). The in situ hybridization study demonstrated EBV-encoded small RNA (EBER)+ cells in all 9 lesions. The immunohistochemical and flow cytometry study demonstrated the reactive nature of the B cells in all 9 lesions. However, 3 of our 7 cases examined demonstrated immunoglobulin heavy chain gene rearrangement on PCR study. There was no development of B cell lymphoma in any of the 3 lesions demonstrating IgH rearrangement. CONCLUSION: EBV-associated LPDs of the WR showed marked histological diversity. Among these, a MALT-like pattern was frequently seen. Marginal zone B cell lymphoma frequently affects WR. We emphasized that EBV-associated LPD should be added to the differential diagnosis of primary tonsillar MALT-type lymphoma.

Recruited peripheral blood monocytes participate in the liver extramedullary hematopoietic milieu.

The hematopoietic microenvironment has been investigated and well defined in the bone marrow. However, there is a lack of studies on the extramedullary hematopoietic milieu such as in the liver, to which hematopoietic stem cells migrate and there commence hematopoiesis under pathological conditions such as bone marrow failure. We induced extramedullary hematopoiesis by phenylhydrazine in the adult mouse liver and investigated the immunohistochemical, ultrastructural, and molecular changes within this organ. Using an intravital lectin injection technique, we found numerous monocytes attached to the central vein prior to hematopoietic foci formation. These cells were later incorporated into the hematopoietic foci. An increase in the mRNA expressions of the monocyte attracting chemokine CCL-2 (MCP-1) was noted in the central vein region as well as in cells within the hematopoietic foci. Together with local liver components, we regard these monocytes as components of the extramedullary hematopoietic milieu. We conclude that the recruitment of extra-hepatic monocytes is an important event during extramedullary hematopoiesis in the liver and that these monocytes participate in the liver hematopoietic microenvironment.

Significance of the progression of respiratory symptoms for predicting community-acquired pneumonia in general practice.

BACKGROUND AND OBJECTIVE: Early diagnosis improves outcomes in patients with community-acquired pneumonia (CAP). However, prediction of CAP based on symptoms and signs is difficult. The present study investigated the evaluation of progression of symptoms as a factor for predicting the occurrence of CAP in general practice. METHODS: Consecutive patients (n = 406) suspected of having CAP on routine clinical examination were studied retrospectively. Selection of patients with suspected CAP was based on progression of symptoms after 5 days, as well as published criteria. Diagnostic yields for the recommended criteria and our proposed criteria were then compared. Scoring systems for the prediction of CAP were designed, based on the results of multiple regression analysis. The diagnostic performance of these systems, including or excluding symptom progression, was compared using the areas under receiver operating characteristic curves. RESULTS: The sensitivity and specificity of the recommended criteria and our proposed criteria were 0.75 and 0.44, and 0.93 and 0.38, respectively. Sputum production, dyspnoea, fever > 38 degrees C, heart rate > 100 beats/min, decreased breath sounds, coarse crackles and progression of symptoms significantly increased the likelihood of CAP. Areas under receiver operating characteristic curves analysis showed that the diagnostic prediction of CAP was significantly improved when the scoring system included progression of symptoms. CONCLUSIONS: Progression of symptoms was a significant factor for predicting CAP and selecting patients who required CXR. Inclusion of progression of symptoms among the other recommended criteria, namely, dyspnoea, fever > 38 degrees C, heart rate > 100 beats/min and abnormal chest findings, improved prediction of the incidence of CAP in general practice.

Cystic cavernous angiomas.

Cystic cavernous angiomas are rarely found in patients. We have reviewed 25 cases of cystic cavernous angiomas, including our case. The patients were predominantly women (15 women and 10 men). The patients' ages ranged from 4 months to 75 years (mean age, 44.0 years). The most frequent symptoms were headache (32%) and cerebellar signs (32%), followed by papilledema (24%), hemiparesis (20%), and seizures (20%). The cystic cavernous angiomas were located in the supratentorial region in 16 (64%) cases, the cerebellopontine angle in 4 (16%) cases, and the cerebellum in 5 (20%) cases. Multiple cystic lesions were observed in only two cases (8%). The typical magnetic resonance images of these patients showed a mixed-intensity nodule on the T1- and T2-weighted images, iso- to high-intensity cysts on the T1-weighted images, and high-intensity cysts on the T2-weighted images. In some of the images, the nodules and cyst walls were enhanced. On the T2-weighted images, the periphery of the cyst showed low intensity. The approach involving total removal of the nodule, partial resection of the cyst, and drainage of the content of the cyst is considered a preferable strategy. Histologically, the nodule showed a network of thin-walled vascular channels lined by endothelium. Hemosiderin deposits and calcification were observed in some cases, and neural tissue was absent. The cyst wall was composed of neocapillary-containing fibrous tissue and showed a proliferation of inflammatory cells and hemosiderin deposits. The etiology of cyst formation remains unclear; however, recurrent hemorrhage from the sinusoids of the vascular malformation or from the neocapillary of the cyst wall and the osmotic transport of water into the cyst are thought to induce the growth of the cyst.

Alteration of angiogenic patterns on B16BL6 melanoma development promoted in Matrigel.

Because the progression and metastasis of solid tumors depend on their local microcirculation, we sought to characterize tumor angiogenesis three dimensionally in a highly metastatic mouse melanoma model, B16BL6 (B16), injected with Matrigel into the subcutis in the skin on the back of syngeneic C57BL/6 mice. We found that B16 with Matrigel grew significantly faster than B16 alone and had altered tumor angiogenesis. Tumor vessels apparently grew vigorously in the opposite direction of the tumor without invading the tumor mass until at least day 10 of injection. In addition, vascular branching resulted not only from sprouting as was seen in B16 without Matrigel but also from vascular splitting, either because of compression from outside the vessels or from septum formation by endothelial cells. This phenomenon was characteristic of B16 cells, but not of other tumor cells, including Lewis lung carcinoma and ASH-1 hybridoma cell lines, both of which were tested under the same conditions. The reduction in various angiogenic factors in Matrigel did not affect the angiogenic patterns and tumor growth. We hypothesize that tumor vessels may vigorously alter their angiogenic patterns in response to the local microenvironment.

Local lymphogenic migration pathway in normal mouse spleen.

Although the immunological and hemodynamical significance of the spleen is of great importance, few reports detail the lymphatic vessels in this organ. We have used an immunohistochemical three-dimensional imaging technique to characterize lymphatic vessels in the normal mouse spleen and have successfully demonstrated their spatial relationship to the blood vascular system for the first time. Lymphatic markers, such as LYVE-1, VEGFR-3, and podoplanin, show different staining patterns depending on their location in the spleen. LYVE-1-positive lymphatic vessels run reverse to the arterial blood flow along the central arteries in the white pulp and trabecular arteries and exit the spleen from the hilum. These lymphatic vessels are surrounded by type IV collagen, indicating that they are collecting lymphatic vessels rather than lymphatic capillaries. Podoplanin is expressed not only in lymphatic vessels, but also in stromal cells in the white pulp. These podoplanin-positive cells form fine meshworks surrounding the lymphatic vessels and central arteries. Following intravenous transplantation of lymphocytes positive for green fluorescent protein (GFP(+)) into normal recipient mice, donor cells appear in the meshworks within 1 h and accumulate in the lymphatic vessels within 6 h after injection. The GFP(+) cells further accumulate in a draining celiac lymph node through the efferent lymphatic vessels from the hilum. These meshworks might therefore act as an extravascular lymphatic pathway and, together with ordinary lymphatic vessels, play a primary role in the cell traffic of the spleen, additional to the blood circulatory system.

MALT type lymphoma demonstrating prominent plasma cell differentiation resembling fibrous variant of Hashimoto's thyroiditis: a three case report.

Fibrous variant of Hashimoto's thyroiditis (HT) is characterized by marked fibrous replacement of one third or more of the thyroid parenchyma. We present here three cases of mucosa associated lymphoid tissue (MALT) type lymphoma demonstrating prominent plasma cell differentiation resembling fibrous variant of HT. Histologically, thyroid structures were disturbed by a diffuse and focally nodular infiltration by mature plasma cells and cells with plasma cell differentiation against a background of prominent hyalinosis. In addition, scattered centrocyte-like (CCL) cells and lymphoepithelial lesions were observed in all three lesions. A portion of the resected specimens in all three cases exhibited HT. However, immunohistochemical study demonstrated that the plasma cells and CCL-cells of these three lesions had monotypic intracytoplasmic kappa light chain. Moreover, these three lesions demonstrated a clonal band on polymerase chain reaction assay for the immunoglobulin heavy chain gene. To avoid underdiagnosis, we emphasize that careful attention should be paid to these immunological features as well as to morphological findings.

Upper gastrointestinal pathophysiology due to mouse malaria Plasmodium berghei ANKA infection.

BACKGROUND: Epigastric pain, vomiting, and other gastrointestinal problems are among the most important symptoms of malaria infection as they suggest the possibility that the condition is serious. Pathophysiologies such as gastric mucosal changes and delayed gastric emptying have been reported in serious cases of malaria infection. However, it is unclear whether or not pathophysiological involvement of the upper gastrointestinal tract occurs in Plasmodium berghei ANKA (PbA)-infected mice. METHODS: PbA-infective Anopheles mosquitoes were used to infect mice via the natural route of infection. Fifteen PbA-C57BL/6 mice were used as a cerebral malaria model and the same numbers of PbA-BALB/c mice were used as a cerebral malaria-resistant model, and then we investigated the pathophysiological involvement of the stomach and small intestine. RESULTS: On day 8 post infection, six PbA-C57BL/6 mice showed cerebral malaria and nine others had uncomplicated infection. All the PbA-C57BL/6 mice on that same day showed severe weight loss with multiple, red gastric patches and changes to the course of the small intestine with villus goblet cell enlargement. In addition, cerebral malaria cases showed gastric gas retention with submucosal edema and small intestinal shortening. In PbA-BALB/c mice, overextension of the stomach and gas retention were evident from week 2 after PbA infection, as well as changes to the course of the small intestine and mesenteric thinning with fragility. CONCLUSIONS: We described the upper gastrointestinal pathophysiology representing new findings directly linked to malarial severity and subsequent death in PbA-infected mice as a mouse model of malaria infection.

Characterization of sinusoidal endothelial cells of the liver and bone marrow using an intravital lectin injection method.

The vascular endothelia express a variety of structural and biological phenotypes. We used an intravital injection method of plant derived lectins (Lycopersicon esculentum lectin (LEL), Ricinus communis Agglutinin-I (RCA-I), Ulex europaeus Agglutinin-I (UEA-I) and Concanavalin A (ConA)) to elucidate the morphology and function of the sinusoidal endothelium of the liver and bone marrow. All four lectins stained the sinusoidal endothelia of the liver and bone marrow in a patchy granular pattern which differed from the uniform and smooth staining pattern of non-sinusoidal vessels in other organs. By transmission electron microscopy, the granular pattern was identified as internalization of these lectins and subsequent accumulation within the endothelial cells, suggesting their active endocytosis. The endocytosis of these lectins emphasizes the fact that sinusoidal endothelial cells of the liver and bone marrow belong to the reticuloendothelial system (RES), a cell system characterized by internalization of foreign material. We introduce this intravital lectin injection as a useful technique to discriminate sinusoidal endothelial of the liver and bone marrow from other vascular endothelia.

Focal lymphoid hyperplasia of the terminal ileum presenting mantle zone hyperplasia with clear cytoplasm. A report of three cases.

We report three unusual cases of focal lymphoid hyperplasia of the ileocecal valve. The gross specimens showed thickening of the ileocecal valve. Low power magnification showed a dense lymphoid infiltrate in the mucosa and submucosa. This condition was characterized by reactive lymphoid follicles with large reactive germinal centers surrounded by a pale cuff of mantle zone lymphocytes presenting a marginal zone distribution pattern. These cells had intermediate- to- medium-sized round or slightly indented nuclei and a broad rim of clear cytoplasm. However, immunohistochemical study demonstrated that both the mantle zone lymphocytes and the pale cuff of the lymphoid cells were CD20+, sIgM+, sIgD+, CD5-, CD10-, CD23-, CD43-, Bcl-2+, Bcl-6-, CyclinD1-. The polytypic nature of these cells was demonstrated by immunohistochemistry and polymerase chain reaction. This unusual mantle cell hyperplasia with clear cytoplasm associated with focal lymphoid hyperplasia in middle-aged and elderly patients should be differentiated from the extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue type or mantle cell lymphoma showing a marginal zone distribution pattern. To avoid overdiagnosis and overtreatment, it is suggested that immunophenotypic and genotypic studies might be required, and careful attention should be paid to the morphologic examination.