[Ibrutinib therapy for a blastoid variant mantle cell lymphoma patient with early extranodal relapse after autologous stem cell transplantation].

A 65-year-old man with multiple lymphadenopathy presented to our hospital and was diagnosed with StageIVA blastoid-variant mantle cell lymphoma (MCL), with a Ki-67 index of 93%. Partial response was achieved after four courses of CHASER (cyclophosphamide, cytarabine, dexamethasone, etoposide, and rituximab) chemotherapy, and complete response was achieved after autologous stem cell transplantation (ASCT). Six months after ASCT, the MCL relapsed with occurrence of tumors one on the left upper arm and one in the cerebrum, which were proved to be resistant to the conventional chemotherapy and progressed rapidly. These tumors disappeared with scarring following the local irradiation (45 Gy). However, the unirradiated regions became enlarged. The bulky abdominal lesion was treated with local irradiation (41 Gy) combined with 560 mg of ibrutinib but still resulted in progressive disease 1 month after initiating the ibrutinib treatment. Finally, the patient died 5 months post-relapse. The prognosis of patients with blastoid-variant MCL with high Ki-67 index is extremely poor. Furthermore, the risk of central nervous system (CNS) involvement is very high. Therefore, ibrutinib maintenance therapy post ASCT might be a treatment option to prevent CNS involvement. Further efforts might be needed to improve the outcomes of blastoid-variant MCL with a high Ki-67 index.

Blastoid Mantle Cell Lymphoma Presenting as an Oropharyngeal Mass.

Blastoid mantle cell lymphoma (MCL) is an extremely rare neoplasm with a dismal prognosis. MCL with an initial presentation in the oral cavity has been rarely reported. This report describes a 75-year-old male who presented with an oropharyngeal mass causing dysphonia and intermittent hypoxia. A biopsy and immunophenotyping confirmed MCL, favoring the blastoid variant. Imaging showed a 4.2 cm left oropharyngeal polypoid mass with extensive lymphadenopathy. His prognosis was considered unfavorable with elevated Ki-67 index, blastoid morphology, and p53 positivity of malignant cells. There was no central nervous system involvement. He received palliative radiation, resulting in profound tumor reduction and resolution of symptoms. An intensive chemoimmunotherapy was not deemed beneficial due to age, comorbidities, absence of TP53 mutation, and a personal preference for a less aggressive treatment. This case highlights the importance of risk-adapted and personalized management approaches in a very unique presentation of blastoid MCL.

Skin Involvement by Hematological Neoplasms with Blastic Morphology: Lymphoblastic Lymphoma, Blastoid Variant of Mantle Cell Lymphoma and Differential Diagnoses.

Hematological neoplasms sharing a blastic morphology may involve the skin. The skin may be either the primary site of occurrence of hematological malignancies with blastic features or cutaneous lesions are the first manifestation of an underlying systemic malignancy. The assessment of skin biopsies of hematological neoplasms with blastic features poses diagnostic problems and requires expert hematopathologists considering a wide range of differential diagnoses. The precise diagnosis of diseases sharing blastic features but with different outcomes and requiring distinct therapies is essential for patient management. The present paper mainly focuses on cutaneous involvement of the blastoid variant of mantle cell lymphoma and lymphoblastic lymphoma of B-cell or T-cell origin. The relevant literature has been reviewed and the clinical aspects, pathological features, prognosis, and therapy of both blastoid mantle cell lymphoma and lymphoblastic lymphoma involving the skin are discussed. A focus on other hematological entities with blastic features, which may involve the skin, to be taken into consideration in differential diagnosis is also given.

Blastoid Mantle Cell Lymphoma of the Palate: Report of a Rare Aggressive Entity and Review of the Literature.

Mantle cell lymphoma (MCL) is a well-defined, non-Hodgkin lymphoma of B-cell origin displaying diverse morphological phenotypes and variable disease course. The World Health Organization recognizes two aggressive histopathologic variants of this type of lymphoma: pleomorphic and blastoid MCL. To date, only few cases of MCL affecting the oral cavity have been reported. Additionally, the involvement of the oral and maxillofacial area by aggressive MCL subsets is considered extremely rare with only two patients reported in the English language literature to the best of our knowledge. Herein, we describe a 69 year-old male with a prior history of MCL of the right lateral pharyngeal wall developing a recurrent lesion extending to the palatal mucosa as diffuse ulceration and exhibiting histomorphological features of blastoid MCL. We also review the pertinent literature with emphasis on the diagnostic challenges and distinction between the different MCL variants.

Blastoid mantle cell lymphoma presenting as acute leukemia: a case report.

Blastoid variant of mantle cell lymphoma (MCL) is an aggressive and incurable form of B-cell lymphoma. Various chemo-immunotherapy regimens have been used with a limited success. Autologous stem cell transplant (ASCT) is being increasingly recommended in first remission for patients with blastoid variant MCL. Here, we describe the case of a 45-year-old lady suffering from blastoid variant of MCL. Patient was administered R-CHOP and underwent autologous stem cell transplant (ASCT). Currently, patient is disease-free and is on a regular follow up for 26 months now. This is an extremely rare case documented in the Indian literature with a long survival post-transplant.

CD5-negative blastoid variant mantle cell lymphoma: a diagnostic dilemma.

We encountered two cases of CD5- blastoid variant mantle cell lymphoma (MCL), prompting us to investigate the proportion of CD5 negativity in MCL and assess the diagnosis of aggressive MCL variants. Among 117 patients diagnosed with MCL, CD5 negativity was observed in 13% (13/104) of cases with classical MCL and 15% (2/13) of cases with blastoid/pleomorphic variant MCL. Of the aggressive MCL variant cases, tumor cells exhibited intermediate nuclear size and required differential diagnosis between blastoid variant and classical MCL in six patients, and classical MCL cells were found in the background of aggressive variant tumors or in other sites in six patients. Of 1534 patients with diffuse large B-cell lymphoma (DLBCL), CD5 positivity was observed in 8% (121/1534) of cases. Immunohistochemical staining for cyclin D1 performed for these cases revealed one cyclin D1-positive and IGH/CCND1 fusion-positive case (0.9%, 1/114), namely pleomorphic variant MCL. Of the remaining 1413 patients initially diagnosed with CD5- DLBCL, the diagnoses of two patients (0.1%) were amended to CD5- blastoid variant MCL in the relapse phase based on morphology, cyclin D1 immunostaining, and fluorescence in situ hybridization. The incidence of CD5 negativity was similar between classical MCL and two aggressive variants. Accurate diagnosis of MCL variants was enabled by identifying a classical MCL component and/or CD5 positivity; however, we misdiagnosed two cases of CD5- blastoid variant MCL. A small number of MCL variants may be included in CD5- DLBCL cases. The diagnosis of CD5- aggressive variant MCL remains challenging but crucial because of its therapeutic significance.

Palatine Tonsils Primary Presentation of Blastoid Variant of Mantle Cell Lymphoma: Case Report.

Head and neck lymphomas can present with a wide range of symptoms. Timely and accurate diagnosis is often challenging. The blastoid variant of mantle cell lymphoma (MCL) accounts for less than one-third of all MCL cases. Isolated primary presentation on the palatine tonsils is rare, and prognosis and outcome are seemingly unfavorable. An 81-year-old man presented with persistent odynophagia, dysphagia, and obstructive hypertrophic palatine tonsils with purulent exudate. The signs and symptoms were non-responsive to antibiotic therapy, and the tonsils were biopsied. The cellular morphology, immunophenotype, and genotype supported a diagnosis of the blastoid variant of MCL. After staging, the patient underwent chemotherapy with Rituximab-Bendamustine (R-Benda). The patient is in clinical remission more than two years after therapy. We report an exceedingly rare case of blastoid MCL that is prone to be misdiagnosed as tonsillitis. We review the literature and discuss treatment options of this uncommon malignancy.

Blastoid variant of mantle cell lymphoma in palatine tonsil.

Blastoid variant of mantle cell lymphoma (MCL) is an aggressive and extremely rare malignancy. MCL may be diagnosed in lymph nodes and/or extranodal sites exhibiting a poor prognosis. MCL with primary presentation in palatine tonsils has been rarely reported. Herein, we report the case of a 73-year-old man with a painless nodular mass on the right palatine tonsil. A biopsy was performed, and microscopic analysis revealed a neoplasm composed of small to medium sized lymphocytes with finely dispersed chromatin, roundish nucleus and many mitoses. The tumor cells were positive for CD20 (L26), CD5 (4C7), Cyclin D1 (EP12), Bcl2 (124) and Ki-67 (MIB-1; 90%), and negative for Bcl6 (PG-B6p), MUM1 (MUM1p) and CD3 (Polyclonal). These findings led to the diagnosis of blastoid variant of MCL. Diagnostic workup with computed tomography scan excluded other sites of disease. The patient was treated successfully with cyclophosphamide, doxorubicin, vincristine and prednisolone (mini-CHOP regimen). Although the blastoid variant of MCL is rare, it should be included in the differential diagnosis of rapid-growing masses in the palatine tonsil.

Blastic Transformation of a Mantle Cell Lymphoma Presenting as an Enlarging Unilateral Orbital Mass.

Mantle cell lymphoma (MCL) is an uncommon form of non-Hodgkin lymphoma predominantly affecting male individuals of advanced age. Approximately 1-9% of cases of lymphoma affecting the orbital and ocular adnexal regions are attributed to MCL. We describe the case of a 65-year-old man with a 24-year history of MCL with initial remission followed by multiple relapses who presented with acute-onset binocular diplopia and proptosis of the left eye. Subsequent imaging demonstrated a new left superior orbital mass. Biopsy of the mass revealed two clonally related, yet distinct cellular components demonstrating the classical mantle cell morphology and large cells that appeared to have transformed to the blastoid variant of MCL. Transformation of classical MCL to the blastoid variant of MCL is rare, with few reports in the literature. The blastoid variant of MCL tends to be aggressive and associated with a poor prognosis. The case we describe represents perhaps the first report of MCL transformation observed in the orbit.

Composite Blastoid Variant of Mantle Cell Lymphoma and Classical Hodgkin Lymphoma.

Composite lymphoma (CL) describes the rare occurrence of 2 or more distinct types of lymphoma in a single anatomical location. We present the case of a 78-year-old man presenting with a 3-month history of weakness, malaise, and increasing dyspnea. A lymph node excised from the posterior triangle of the neck revealed the coexistence of 2 morphologically and phenotypically distinct lymphoid neoplasms consistent with a blastoid variant of mantle cell lymphoma (MCL) occurring in composite with classical Hodgkin lymphoma (cHL), mixed cellularity subtype. A t(11;14)(q13;q32) translocation was demonstrated by fluorescence in situ hybridization in the MCL and Hodgkin Reed-Sternberg cells of the cHL. Multiplex polymerase chain reaction detected clonal Immunoglobulin heavy chain (VFR1-J, VFR2-J, and VFR3-J), clonal immunoglobulin light chain kappa (V-J and V/JC intron-kde) and clonal immunoglobulin light chain lambda (V-J) gene rearrangements in the MCL. This report represents the first case of a blastoid variant of MCL occurring in composite with cHL.

Classical type and blastoid variant mantle cell lymphoma in the same lymph node: Histology and cytological findings from a touch imprint specimen.

Blastoid variant (BV) is one of the aggressive variants of mantle cell lymphoma (MCL). BV-MCL is defined by its blastic cytomorphology. Previous studies using sequential biopsies in cases with MCL have demonstrated that classical type MCL (C-MCL) often transforms or relapses as an aggressive variant, but a histopathological transition from C-MCL to an aggressive MCL variant in the same pathological specimen has been shown in only a limited number of the cases. We present a case of MCL in which a histological transition between C-MCL and BV-MCL was observed in the same lymph node. A 53-year-old man presented with a submandibular tumor. Touch imprint cytology revealed a monotonous proliferation of large blastic lymphoid cells. Histology revealed a transition between a large lymphoid cell component and small foci of small- to medium-sized cell component within the tumor. Both components were CD5(+), CD10(-), CD20(+), cyclin D1(+), and SOX11(+) on immunohistochemistry. Fluorescent in situ hybridization revealed the translocation of IgH/BCL1 locus. These findings led to a final diagnosis of BV-MCL with coexistent C-MCL. The present case suggests the existence of a pathogenetic pathway of MCL from C-MCL to BV-MCL. Because it is important to accurately identify BV-MCL for prognostication, appropriate ancillary diagnostic tools should be used in suspected cases. Diagn. Cytopathol. 2017;45:364-370. © 2016 Wiley Periodicals, Inc.

Clinicopathologic features, management and outcomes of blastoid variant of mantle cell lymphoma: a Nebraska Lymphoma Study Group Experience.

The objective of this retrospective study (N = 169) was to compare the overall survival (OS) of different subtypes of mantle cell lymphoma (MCL) treated by the Nebraska Lymphoma Study Group between 1984 and 2012. The overall response rate to various therapies including stem cell transplant (SCT) was similar (p = 0.44) between blastoid, diffuse and nodular subtypes. At 5 years, blastoid and diffuse subtypes had worse OS (overall p = 0.005) compared to nodular subtype. In multivariate analysis, the blastoid and diffuse subtypes had similar risk of death (p = 0.14) whereas the nodular subtype had a lower risk compared to blastoid (HR 0.48, 95% CI 0.27-0.87, p = 0.01). The use of SCT was associated with lower risk of death. In univariate analysis, blastoid subtype had better OS with intensive upfront therapy. In conclusion, the OS of blastoid subtype is worse than nodular MCL but may improve with the use of SCT and probably intensive induction therapy.

Clinicopathologic features and management of blastoid variant of mantle cell lymphoma.

The blastoid variant of mantle cell lymphoma (MCL), which accounts for less than one-third of MCL, may arise de novo or as a transformation from the classical form of MCL. Blastoid variant, which predominantly involves men in their sixth decade, has frequent extranodal involvement (40-60%), stage IV disease (up to 85%) and central nervous system (CNS) involvement. Diagnosis relies on morphological features and is challenging. Immunophenotyping may display CD23 and CD10 positivity and CD5 negativity in a subset. Genetic analysis demonstrates an increased number of complex genetic alterations. Blastoid variant responds poorly to conventional chemotherapy and has a short duration of response. Although the optimal therapy remains to be established, CNS prophylaxis and the use of aggressive immunochemotherapy followed by autologous stem cell transplant may prolong the remission rate and survival. Further studies are crucial to expand our understanding of this disease entity and improve the clinical outcome.