Current World Health Organization Classification Research Articles

Hepatocyte nuclear factor‐1 α inactivated hepatocellular adenomas in patient with congenital absence of the portal vein: A case report

Hepatocellular adenomas (HCAs) have been recognized recently as a heterogeneous group, and are subclassified according to genotype as well as morphological characteristics. We report a case of a 35-year-old Japanese woman who exhibited hepatocyte nuclear factor (HNF)-1α-inactivated HCA in the background of the congenital absence of the portal vein (CAPV). On a dynamic contrast computed tomography (CT) scan, the hypovascular tumor enlarged from 1 cm to 3 cm and another tumor emerged in the course of 7 years. Because the possibility of hepatocellular carcinoma (HCC) with multiple metastases was not excluded, partial hepatectomy was performed. On a cut section, two well-demarcated tumors were observed and one tumor had a central fibrous scar. The histological features of these tumors were similar to those of focal nodular hyperplasia (FNH) with a central scar and HCA; however, these tumors were diagnosed as HNF-1α-inactivated HCA by immunohistochemistry according to the criteria of the current World Health Organization (WHO) classification. In non-tumorous liver tissue, an abnormal architecture of the vessels and a vague nodular appearance of lobuli were observed, which were likely to be those of nodular regenerated hyperplasia (NRH). We discuss its pathogenesis and relationship with CAPV.

Columnar Cell Variant of Papillary Thyroid Carcinoma: A Study of 10 Cases with Emphasis on CDX2 Expression

Columnar cell variant is a recognized rare variant of papillary thyroid carcinoma (PTC) that has an uncertain clinical course. This variant has two subvariants, and one is regarded as a more aggressive form in comparison to the more common classical and follicular variants. These tumors have morphological resemblance with endometrial or colonic adenocarcinoma. CDX2, a transcription factor of the caudal homeobox family, plays a key role in intestinal development and differentiation, and it is widely used as a marker to detect adenocarcinomas of intestinal and colonic origin. CDX2 has been rarely reported in PTC. We studied 10 cases of columnar cell variant of PTC (CCV-PTC). The histological, architectural, and cytological features fulfilled the diagnostic criteria of the CCV-PTC, as defined by the current World Health Organization classification. Ten patients (six men and four women) ranging in age from 32 to 90 years (mean, 58.3 years) presented with tumors classified as indolent (four cases) or aggressive (six cases); three harbored a BRAF(V600E) mutation. All cases were β-catenin negative. The Ki-67 proliferative index was up to 50%. All cases were thyroid transcription factor-1-positive. Using paraffin-embedded blocks, immunohistochemistry for CDX2 was performed to evaluate the reactivity of this antibody to this variant of PTC. Nuclear positivity for CDX2 was detected in one out of the 10 cases studied (10%); the other nine cases did not express CDX2. Only one of our cases showed nuclear positivity for CDX2. Therefore, our study failed to confirm it as a marker for CCV-PTC. The absence of CDX2 in the majority of the cases does not support the theory of CDX2 playing a role in the intestinal phenotype of these tumors.

CEBPA double-mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76·8% of cases with TET2 and GATA2 alterations impacting prognosis.

Acute myeloid leukaemia (AML) with CEBPA mutations is listed as a provisional entity in the current World Health Organization classification. A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported, whereupon CEBPAdm cases were shown to be associated with better overall survival (OS). The occurrence and prognostic impact of concomitant molecular mutations in addition to CEBPAdm has not been assessed until now with exception of GATA2 mutations. Here, we investigated a cohort of 95 AML CEBPAdm cases for concomitant mutations. TET2 was found to be most frequently mutated (34·0%) gene, followed by GATA2 (21·0%), WT1 (13·7%), DNMT3A (9·6%), ASXL1 (9·5%), NRAS (8·4%), KRAS (3·2%), IDH1/2 (6·3%), FLT3-internal tandem duplication (6·3%), FLT3-tyrosine kinase domain (2·1%), NPM1 (2·1%), and RUNX1 (1/94). Patients harbouring additional mutations in the TET2 gene showed significantly worse OS than TET2 wild-type cases (P=0·035), whereas GATA2-mutated patients showed improved OS (P=0·032). Serial analyses were performed for 39 CEBPAdm cases with concomitant mutations. Here, we observed that CEBPA mutations present the primary pathogenetic event in the majority of cases (76·9%). Further, a distinct gene expression profile (GEP) was confirmed for CEBPAdm versus CEBPAsm or CEBPA wild-type cases while no significant changes in GEP were observed related to additional mutations within the CEBPAdm AML.

Endometrial sarcomas: an immunohistochemical and JAZF1 re-arrangement study in low-grade and undifferentiated tumors

The current World Health Organization classification divides endometrial sarcomas into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma. Recent studies suggest undifferentiated endometrial sarcoma is a heterogeneous group and a subgroup with uniform nuclei is more akin to low-grade endometrial stromal sarcoma in terms of morphologic, immunohistochemical and genetic features. We classified endometrial sarcomas treated at our institution from 1998 to 2011 into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma, the latter being further categorized into a group with either uniform or pleomorphic nuclei. Morphological features, immunoprofile and fluorescence in situ hybridization rearrangements of JAZF1 and PHF1 genes were correlated with tumor category and outcome. A total of 40 cases were evaluated comprising 23 low-grade endometrial stromal sarcomas, 10 undifferentiated endometrial sarcomas with nuclear uniformity and 7 undifferentiated endometrial sarcomas with nuclear pleomorphism. Low-grade endometrial stromal sarcomas were more often estrogen and progesterone receptor positive (83%) compared with undifferentiated endometrial sarcoma with nuclear uniformity (10%) or with nuclear pleomorphism (0%) (P<0.001). Positivity for p53 was restricted to undifferentiated endometrial sarcomas with more frequent expression in the group with nuclear pleomorphism (57%) than with nuclear uniformity (10%) (P=0.06). Ki-67 proliferation index in >10% of tumor cells more frequent in undifferentiated endometrial sarcoma than low-grade endometrial stromal sarcoma (P=<0.001). JAZF1 rearrangement was detected in 32% of low-grade endometrial stromal sarcomas and in none of the undifferentiated sarcomas. Rearrangement of PHF1 was found in two patients, one with JAZF1−PHF1 fusion. There were no significant differences in clinical behavior between undifferentiated endometrial sarcoma with nuclear uniformity versus nuclear pleomorphism. In conclusion, we found undifferentiated endometrial sarcoma subtypes and low-grade endometrial stromal sarcoma have distinct immunohistochemical and cytogentic profiles. Our data do not show any difference in clinical behavior between subgroups in undifferentiated sarcomas.

Finding and Characterizing Mammary Analogue Secretory Carcinoma of the Salivary Gland

BackgroundA new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features.MethodsThirty cases of MASC candidates were selected after review of 196 salivary gland tumors, and subjected to break-apart ETV6 fluorescence in situ hybridization (FISH), and immunohistochemical study for S100 protein, gross cystic disease fluid protein 15, DOG1, estrogen receptor, and progesterone receptor.ResultsValid FISH results were obtained in 23 cases, and 13 positive cases were retrieved. MASCs were histologically varied, and the most frequent features observed in 10 cases were low-grade papillary/cystic/glandular patterns, intraluminal secretory materials, ovoid/wrinkled nuclei, and relatively abundant granular eosinophilic cytoplasms, corresponding to papillary-cystic or follicular types of AciCC. All cases showed diffuse immunopositivity for S100 protein. Three cases developed recurrences, but all patients remained alive.ConclusionsMASC could be a molecularly well-defined salivary gland neoplasm, encompassing some portions of AciCC and ANOS, but its histological spectrum and clinical implication require further investigation.

Aspectos clinicopatológicos y moleculares de valor diagnóstico y pronóstico en gliomas

Diffuse infiltrative gliomas, the most common primary brain tumours, account for almost 80% of malignant brain tumours. 60-70% of gliomas are astrocytic and over 80% of these tumours is considered high grade malignancy (grade III and IV) according to current World Health Organization classification. Infiltrating gliomas include diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas. To review the clinical and histological features of cerebral gliomas, and molecular alterations that add relevant information for novel approaches in diagnosis, prognosis and treatment. The current gold standard diagnosis of these tumours relies on histopathological classification, which provides a grading of malignancy as a predictor of biological behaviour. However emerging molecular abnormalities have been discovered in the last years and these molecular changes are playing an increasingly prominent role as predictive biomarkers or in the development of diagnostic and prognostic. Now the neuropathologist is in crossroads between pathology and molecular biology and he plays a significant role in implementation of treatments and/or clinical trials. The study of proteomics and molecular biomarkers should complement the histopathological analysis and sometimes allows to determine direct or indirect predictive factors as well as the study of affected pathways which may become selective therapeutic targets.

Micronodular Thymoma with Lymphoid Stroma in a Multilocular Thymic Cyst: A Case Study

Herein, we report a case of micronodular thymoma with lymphoid stroma in a previously healthy 73-year-old male. Thymectomy was performed. The solid and macrocystic masses were encapsulated with focal invasion. The solid portion consisted of nodules of bland-looking spindle or round epithelial cells in lymphoid stroma containing prominent germinal centers. The epithelial cells had moderate amount of cytoplasm and occasional mucin production. The cystic portion was lined with cuboidal epithelium. According to World Health Organization (WHO) classification, the mass was diagnosed as a micronodular thymoma with lymphoid stroma accompanied by a pre-existing multilocular thymic cyst. Micronodular thymoma with lymphoid stroma, a possible variant of type A thymoma, is an extremely rare tumor. This so-called "unusual" variant may imply the schematic weakness of the current WHO classification that cannot cover all morphologic types. Further study is recommended for clarification of this variant and its incorporation into the current classification.

Colorectal mixed adeno-neuroendocrine carcinomas

Mixed adeno-neuroendocrine carcinomas (MANEC) are rare gastrointestinal neoplasms most commonly diagnosed in the large bowel. They contain mixed exocrine and endocrine components and for diagnosis at least 30% of either component must be identi-fied. We present two recent cases, the first of which was a 69-year-old male who presented with anaemia and weight loss and was found to have a rectal tumour. He received combined chemo-radiotherapy and subsequent surgery revealed a 15 mm MANEC invading into the perirectal tissue. The tumour showed radiation-induced changes with neuroendocrine carcinoma adjacent to ad-enocarcinoma. The second case was a 75-year-old male who presented with obstructive symptoms and a palpable abdominal mass. Following surgery, he was found to have a 95 mm MANEC in the ascending colon invading into the pericolic tissue. Both cases were confirmed using neuroendocrine immunohistochemical markers. Positive staining of the neuroendocrine components was seen with at least two of CD56, synaptophysin and chromogranin. The current World Health Organization (2010) classification recognises that size >20 mm, invasion of the muscularis propria, lymphatic invasion and atypical histology are significant risk factors for malignant behaviour. The two cases presented contain most, if not all of these factors.

Cutaneous EBV‐positive γδ T‐cell lymphoma vs. extranodal NK/T‐cell lymphoma: a case report and literature review

Primary cutaneous γδ T-cell lymphoma and extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type are two distinct lymphoma entities in the World Health Organization (WHO) classification. We report the case of an aggressive cutaneous lymphoma of γδ T-cell origin showing overlapping features of both lymphomas. A 78-year-old female presented with confluent erythematous plaques with ulcerations over her right thigh. Microscopically, section of the skin showed a diffuse dermal and subcutaneous lymphocytic infiltration with tumor necrosis and angioinvasion. The medium- to large-sized tumor cells expressed CD3, CD8, cytotoxic molecules and T-cell receptor (TCR)-γ but not CD4, CD20, CD30, CD56 or βF1. In situ hybridization for Epstein-Barr virus-encoded mRNA (EBER) was diffusely positive. Polymerase chain reaction-based clonality assay showed a clonal TCR-γ chain gene rearrangement. The features compatible with γδ T-cell lymphoma include dermal and subcutaneous involvements, cytotoxic phenotype, expression of TCR-γ, as well as an aggressive course. On the other hand, the diffuse EBER positivity, angioinvasion, tumor necrosis and cytotoxic phenotype may also fit in the diagnosis of an ENKTL of T-cell lineage. We review the literature on EBER-positive γδ T-cell lymphoma and discuss the diagnostic dilemma using the current WHO classification system.

Diagnostic reproducibility of thymic epithelial tumors using the World Health Organization classification: note for thoracic clinicians

Histopathological diagnosis of thymic epithelial tumors according to the current World Health Organization classification is not adequately reproducible; however, most thoracic clinicians are unaware of this. We illustrate this problem in practical settings to raise clinician awareness. An expert pathologist specialized in thymic pathology and a trained general pathologist independently diagnosed 158 resected thymic epithelial tumors. Assuming that the expert's diagnoses were more accurate, the two pathologists' diagnoses were judged to be concordant when tumor subtypes (thymoma) or categories (thymic carcinoma and neuroendocrine tumor) were in agreement. The concordance rates for different thymoma subtypes were 75 % (3/4), 30 % (11/37), 100 % (17/17), 80 % (39/49), and 53 % (9/17) for types A, AB, B1, B2, and B3, respectively. Discordant cases of type AB thymoma were mainly diagnosed as type B1 or B2 by the general pathologist. Discordant cases of type B2 thymoma were diagnosed as type AB, B1, or B3, and discordant cases of type B3 thymoma were diagnosed as type A, B2, or carcinoma. Discordant cases of thymic carcinoma were diagnosed as type A or B3 thymoma. Investigation of the concordant and discordant cases suggested that reasonable discrepancies can occur because of the noncommittal categorical boundaries inherent in this classification. Thoracic clinicians should consider this potential problem in daily practice.

Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Bone marrow morphology predicts additional chromosomal abnormalities in patients with myelodysplastic syndrome with del(5q)

The current World Health Organization classification considers myelodysplastic syndrome with isolated del(5q) a distinct entity owing to its characteristic clinical and pathologic features. Recently, several studies have examined survival, leukemic transformation, and various prognostic factors in these patients. However, there is a lack of detailed comparative pathologic analysis of myelodysplastic syndrome cases in which del(5q) is present in association with additional cytogenetic abnormalities. We studied 26 cases of myelodysplastic syndrome at initial diagnosis with 5q- alone, 5q- plus 1 additional abnormality, and 5q- as part of a complex karyotype. Four of 17 patients had evidence of JAK2 V617F mutation. In contrast to cases of myelodysplastic syndrome with isolated 5q-, patients with additional abnormalities had normal mean corpuscular volume and decreased platelet counts (P < .001). Based on bone marrow examination, they were significantly more likely to have increased cellularity, trilineage dysplasia, lower proportion of small hypolobated megakaryocytes, higher number of blasts, and fibrosis. The presence of these morphologic features can be used to distinguish these more aggressive cases from those with myelodysplastic syndrome with isolated 5q- and a more benign clinical course.

Biomarkers Classification and Therapeutic Decision-Making for Malignant Gliomas

Diffuse gliomas are the most common primary brain tumors, with glioblastoma (GBM) encompassing more than 50 % of all cases. Despite aggressive therapy, patients nearly always succumb to their disease and the survival for patients with GBM is approximately 1 year. During past years, numerous scientific contributions have reshaped the field of neuro-oncology and neuropathology. A series of molecular discoveries have shed light on new pathogenic mechanisms, as well as new prognostic and predictive biomarkers with clinical relevance. The current World Health Organization (WHO) classification system is solely based on morphologic criteria; however, there is accumulated evidence that tumors with similar histology have distinct molecular signatures with a clinically significant impact on treatment response and survival. Molecular markers and signatures could be incorporated into the glioma classification and grading system to mirror the clinical outcomes. Additionally, molecular markers could lead to a redefinition of currently controversial entities, such as mixed oligoastrocytomas. Newly discovered molecular alterations also have the potential to become targets for future drug development. Despite tremendous progress in the past decade, therapeutic progress for diffuse gliomas has been slow. A further understanding of glioma biology, in concert with well-designed clinical trials, is necessary to identify more putative molecular biomarkers and unravel the mysteries in the pathogenic mechanisms that trigger this menacing disease.

Follicular T-cell lymphoma: a member of an emerging family of follicular helper T-cell derived T-cell lymphomas

Unlike B-cell lymphomas, where knowledge of normal B-cell origin and differentiation has greatly contributed to their classification, the current classification of peripheral T-cell lymphomas is limited by a lack of understanding of their cellular origin. In the current World Health Organization classification of lymphomas, follicular T-cell lymphoma was formally recognized as a morphologic variant of peripheral T-cell lymphoma, not otherwise specified. There is growing evidence, however, that follicular T-cell lymphoma may be a unique clinicopathologic entity based on its morphologic features and derivation from follicular helper T-cells. In addition, there are abundant recent data supporting the concept that follicular helper T-cells can give rise to other types of T-cell lymphoma, including angioimmunoblastic T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoma, and a subset of neoplasms, in addition to follicular T-cell lymphoma, currently classified as peripheral T-cell lymphoma, not otherwise specified. In this review, we focus primarily on the clinicopathologic, immunophenotypic, and molecular features of follicular T-cell lymphoma and discuss its potential relationship with other types of T-cell lymphoma thought to be derived from follicular helper T-cells.

Microscopic Diffuse Large B-Cell Lymphoma (DLBCL) Occurring in Pseudocysts

We report 2 cases of localized, microscopic diffuse large B-cell lymphoma (DLBCL) that were detected incidentally within pseudocysts. In case 1, the neoplasm was identified within a 26-cm, 860-g adrenal gland pseudocyst. In case 2, the neoplasm was detected within a 9-cm, 90-g paratesticular pseudocyst. In both cases, the neoplastic cells were large, had a nongerminal center B-cell immunophenotype, and were positive for Epstein-Barr virus (EBV)-encoded RNA detected by in situ hybridization. The most appropriate classification of these tumors using current World Health Organization classification is uncertain. The best fit seems to be DLBCL associated with chronic inflammation (DLBCL-CI), defined as DLBCL arising in the context of long-standing chronic inflammation and associated with EBV infection, with the prototype for this category being pyothorax-associated lymphoma. This term has been used by others in the literature for tumors similar to the cases reported here. However, in the 2 cases we report chronic inflammation was not a prominent feature, and the inflammatory cells that were present showed little relationship to the lymphoma cells. The findings in these cases have led us to question the role of chronic inflammation in pathogenesis. Perhaps the closed space of the pseudocyst, by preventing a cytolytic response to EBV-infected cells, results in local immunodeficiency that may be most important for pathogenesis. We also have concerns about using the term DLBCL-CI for these tumors. Perhaps the cases we report and the few other similar cases reported previously deserve their own category in a future version of the World Health Organization classification.

The spectrum of lymphoblastic, nodal and extranodal T-cell lymphomas: characteristic features and diagnostic dilemmas

T-cell lymphomas represent a heterogeneous group of neoplasms that encompass considerable clinical, morphologic, and immunophenotypic variation. The diagnosis of T-cell lymphoma is challenging because of its relative rarity, the lack of an immunophenotypic marker of clonality, and significant morphologic overlap with infectious/inflammatory processes and neoplasms, including Hodgkin and other non-Hodgkin lymphomas, and even mesenchymal or epithelial lesions. In the current World Health Organization classification of hematopoietic tumors, all except 1 subtype (ie, T-lymphoblastic lymphoma) are recognized as mature neoplasms derived from postthymic T cells. In addition to T-lymphoblastic lymphoma, this review will focus on nodal and extranodal T-cell lymphomas and exclude T-cell lymphomas presenting primarily in the skin. Extranodal natural-killer-cell/T-cell lymphoma, nasal type, will also be discussed because the derivation of this lymphoma from natural killer and natural killer-like T cells shows morphologic and immunophenotypic features that overlap with other T-cell lymphomas. In this review, we discuss the salient clinicopathologic, immunophenotypic, and genetic features, as well as our approaches to the diagnosis of lymphoblastic, nodal, and extranodal T-cell lymphomas.

NK/T-Cell Lymphomas: Pathobiology, Prognosis and Treatment Paradigm

The current World Health Organization (WHO) classification includes two types of natural killer (NK)-cell lymphomas: extranodal NK/T-cell lymphoma, nasal type (ENKL), and aggressive NK-cell leukemia (ANKL). These diseases are mostly endemic to East Asia and Latin America. The Epstein-Barr virus (EBV) is usually detected in tumor cells, suggesting that EBV plays an important role in lymphomagenesis. At the site of origin, ENKL can be divided into two major subtypes: nasal and extranasal diseases. The advanced disease presentation, highly aggressive clinical course, and poor prognosis of the latter are analogous to ANKL. It is well known that P-glycoprotein, which is a product of the multi-drug resistance (MDR1) gene, is expressed on neoplastic cells of ENKL or ANKL. This is a major cause of the refractoriness of malignant lymphoma to conventional chemotherapeutic regimens containing anthracycline. Recent studies, however, have identified that L-asparaginase-containing regimens, such as SMILE (steroid, methotrexate, ifosfamide, L-asparaginase and etoposide), are effective for ENKL. Considering the myelotoxicity of SMILE, its use in the treatment of ANKL needs some modifications, but this treatment scheme is promising in improving the prognosis of NK-cell lymphomas.

An Unusual Form of Superficially Disseminated Glioma in Children

Three children, aged 4, 5, and 9 years, had an insidious onset of ataxia. Magnetic resonance imaging (MRI) showed hydrocephalus and countless foci of high T2 signal coating the cerebellum, basilar cisterns, brainstem, and fourth ventricle. Similar lesions were present in the spinal cord. Symptoms were relatively mild given the massive tumor burden. Biopsies were composed of superficially infiltrating cells with oligodendroglioma-like features (perinuclear halos and cytologic monotony) and microcysts. Classical cytogenetic analysis of 2 cases showed normal karyotypes. Chromosome fluorescence in situ hybridization revealed 1p36 deletion with intact 19q in 2 cases and no abnormality in one. A similar combination of clinical, MRI, and histopathologic findings has been reported previously in 10 other cases. The pathologic findings suggest a glioma with diffuse or multifocal superficial origin and do not correspond to a described entity in the current World Health Organization (WHO) classification of brain tumors.

World Health Organization Classification of Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are characterized by an ineffective hematopoiesis and functional abnormalities of hematopoietic lineages. Patients with MDS present with cytopenia(s) associated with morphological dysplasia and /or increase in number of blasts, and can progress to acute myeloid leukemia. The pathogenesis of MDS is exceedingly complex and involves the hematopoietic stem cells, bone marrow microenvironment and an interaction between these two compartments. The laboratory diagnostic strategy in MDS has evolved significantly over the years from a purely morphological one based almost exclusively on peripheral blood smear and bone marrow aspirate cytology to the integrated multiparametric approach used in the 2001 and 2008 WHO classification schemes. An evolution has also occurred in the prognostic assessment and the evaluation of treatment response to include novel disease related factors as well as patient specific characteristics such as non-hematologic comorbidities. This progress in clinically relevant subclassification of MDS and inclusion of specific variables related to treatment response are particularly important considering the increasing treatment options available for MDS. This review is largely focused on the diagnostic approach to MDS including discussion of the significance of cytogenetic/genetic and immunophenotypic features. We present the overview of the minimal diagnostic criteria for diagnosing MDS and a detailed description the current World Health Organization (WHO) classification scheme.

Two cases of mantle cell lymphoma mimicking marginal zone lymphoma

Mantle cell lymphoma (MCL) is a B cell lymphoma with four morphologic variants recognized by the current World Health Organization classification. MCL mimicking marginal zone lymphoma (MZL) (MCL mimicking MZL) is the rarest variant and could be a potential diagnostic pitfall due to its deceiving “monocytoid” appearance. We report two cases of extranodal MCL mimicking MZL occurring at different sites—the oropharynx and the rectosigmoid colon. Both cases showed unexpected diffuse submucosal lymphoid infiltration of small- to medium-sized lymphocytes with focal monocytoid appearance. Immunohistochemistry showed the presence of an abnormal CD5(−)/CD10(−) B cell population expressing cyclin D1. The diagnosis of MCL was further substantiated by cytogenetic evidence of t(11;14)(q13;q32). Ki-67 proliferation indexes of both cases were low. In summary, MCL mimicking MZL may have unusual morphologic and immunophenotypic characteristics that could be a diagnostic pitfall.