Large Lymphoid Cells Research Articles

Fatal Case of EBV-negative Posttransplant Lymphoproliferative Disorder With Hemophagocytic Lymphohistiocytosis in an Adult Kidney Transplant Recipient.

Fatal Case of EBV-negative Posttransplant Lymphoproliferative Disorder With Hemophagocytic Lymphohistiocytosis in an Adult Kidney Transplant Recipient.

Malar rash with pancytopenia

Malar rash with pancytopenia

Unveiling the journey of diagnosing cutaneous lymphomas- A case series

Cutaneous manifestation of Non-Hodgkin lymphoma can histologically and clinically manifest as Mycosis fungoides or Vasculitis. Histopathologic features of cutaneous lymphoma show dense tumor with a “bottom heavy” configuration. Tumor comprises either large lymphoid cells or sheets of monotonous small lymphoid cells with plasmacytoid configuration. A detailed work up is mandatory to conclude the diagnosis and provide definitive treatment in cutaneous lymphomas. In our case series, we present and describe 5 cases of Non-Hodgkin lymphoma with cutaneous manifestations. Two cases of Angioimmunoblastic T Cell Lymphoma with clinical and histological presentation as vasculitis, 2 cases of Mycosis fungoides concluded as Human T-cell Lymphotrophic Virus (HTLV) positive Adult T Cell Lymphomas on evaluation, 1 case which was lost to follow up are discussed. Thus, this case series emphasizes on the need to do complete work up of cutaneous lymphomas.

Anaplastic Large Cell Lymphoma: Molecular Pathogenesis and Treatment.

Simple SummaryAnaplastic large cell lymphoma is a rare type of disease that occurs throughout the world and has four subtypes. A summary and comparison of these subtypes can assist with advancing our knowledge of the mechanism and treatment of ALCL, which is helpful in making progress in this field.Anaplastic large cell lymphoma (ALCL) is an uncommon type of non-Hodgkin’s lymphoma (NHL), as well as one of the subtypes of T cell lymphoma, accounting for 1 to 3% of non-Hodgkin’s lymphomas and around 15% of T cell lymphomas. In 2016, the World Health Organization (WHO) classified anaplastic large cell lymphoma into four categories: ALK-positive ALCL (ALK+ALCL), ALK-negative ALCL (ALK−ALCL), primary cutaneous ALCL (pcALCL), and breast-implant-associated ALCL (BIA-ALCL), respectively. Clinical symptoms, gene changes, prognoses, and therapy differ among the four types. Large lymphoid cells with copious cytoplasm and pleomorphic characteristics with horseshoe-shaped or reniform nuclei, for example, are found in both ALK+ and ALK−ALCL. However, their epidemiology and pathogenetic origins are distinct. BIA-ALCL is currently recognized as a new provisional entity, which is a noninvasive disease with favorable results. In this review, we focus on molecular pathogenesis and management of anaplastic large cell lymphoma.

Primary Cutaneous Anaplastic Large Cell Lymphoma: A Rare Case Report in a Young Soldier

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) usually presents with scaly patches or plaques and nodular skin lesion. Most people with C-ALCL have indolent (i.e., chronic, slow growing) lymphomas which are treatable and curable. Histologically cutaneous anaplastic large cell lymphoma is diffuse, non-epidermotropic with anaplastic large lymphoid cells. Immunohistochemically most of the tumor cells express CD30 antigen and prognosis is good. Excision of the lesion followed by radiotherapy and/or low dose methotrexate are the treatment of choice. The present study reports a rare case of 30-year-old-man presenting with multifocal papulonodular lesions in the right forearm and biopsy confirmed that the case is cutaneous anaplastic large-cell lymphoma. He was treated with low dose of methotrexate and patient became completely cured without any residual disease. JAFMC Bangladesh. Vol 17, No 1 (June) 2021: 46-48

ALK-positive large B-cell lymphomas: A clinicopathologic study.

Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphomas (ALK+-LBCLs) are aggressive CD20-negative lymphomas, accounting for <1% of diffuse LBCLs. Being rare and with peculiar immunophenotypic characteristics, these can be easily misdiagnosed. We present 11 cases of ALK+-LBCLs diagnosed over a period of 11 years at a tertiary care hospital in South India to analyze the clinical, morphological, and immunophenotypic profile of these tumors. ALK+-LBCL cases diagnosed from September 2009 to August 2020 were included. Clinical details were obtained from stored electronic records and summarized. Available hematoxylin and eosin (H and E) stained slides and immunohistochemistry slides were reviewed and observations tabulated. Eleven patients (nine males and two females) were diagnosed with ALK+-LBCLs in the study period with seven presenting primarily with extranodal disease manifestations. Tumors in the lymph nodes showed diffuse architecture effacement and variable sinusoidal invasion. All tumors showed immunoblastic and plasmablastic-type large lymphoid cells with scattered anaplastic/multinucleate large cells, including rare Reed-Sternberg-like cells. Cytoplasmic granular ALK-1 staining, CD20 negativity, and immunohistochemical features of plasmablastic differentiation were noted in all. Of eight patients treated, only one achieved remission with multi-agent chemotherapy but relapsed after 6 months. Two patients died of disease and five others had progressive/persistent disease and were lost to follow-up. Although rare, these tumors should always be in the differential diagnoses of tumors with plasmablastic and immunoblastic morphology, especially in extranodal sites to avoid diagnostic delay/misdiagnosis.

EBV-positive Diffuse Large B-Cell Lymphoma, NOS in a Filipino Patient: Mimickers and Essential Ancillary Studies

Epstein-Barr virus positive diffuse large B-cell lymphoma (EBV+ DLBCL) is prevalent among Asians but is underreported in the Philippine setting. We report the case of an 88-year-old male who presented with difficulty swallowing. CT scan showed an ill-defined soft tissue focus with calcifications in the supraglottic to hypopharyngeal region measuring approximately 2.6 x 1.7 x 1.5 cm, and multiple lymphadenopathies in the head and neck. Biopsy of the masses at the left tonsil, left arytenoid mucosa, pyriform sinus, and aryepiglottic fold showed large lymphoid cells with several Reed-Sternberg-like cells in a background of small lymphocytes, neutrophils, few eosinophils and histiocytes. A panel of immunohistochemical stains and EBER-ish were performed to differentiate among six entities that were morphologically similar to the patient’s case, namely, classic Hodgkin lymphoma, T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), DLBCL, NOS, anaplastic variant, B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic HL (gray zone lymphoma), and infectious mononucleosis (IM). The neoplastic cells expressed CD20, CD30, CD45, PAX5, CD10, MUM-1, BCL6, BCL2, and c-myc, while CD3, CD15 and ALK-1 were negative. The cells of interest also showed nuclear staining (30-40%) on Epstein-Barr virus encoding RNA in-situ hybridization (EBER-ish). The Ki-67 showed a proliferation index of 40-50%. Given the differences in prognosis and treatment among these diseases, judicious use of immunostains and EBER-ish is recommended for accurate diagnosis.

Florid Lymphoid Hyperplasia or Lymphoma-like Lesion of the Lower Genital Tract: A 35-Year Literature Review in View of the New WHO Classification.

Florid lymphoid hyperplasias of the lower female genital tract, also known as pseudolymphoma or lymphoma-like lesions, are benign lesions displaying histologic features which mimic aggressive B-cell lymphomas. Initially described by Young and colleagues in 1985, fewer than 100 cases have been published, making this lesion rather uncommon and subject to misdiagnoses. However, given that this entity has now been included in the World Health Organization's most recent classification, greater clarity would be beneficial for pathologists and physicians. Thus, our report aims to review these entities and provide all available data. We reviewed the available literature according to PRISMA guidelines. We found that lymphoma-like lesions, regardless of their localization, display numerous superficial lymphoid B cells admixed with a polymorphic small lymphocytic and plasmocytic background and, sometimes, superficial ulceration. Large lymphoid cells show prominent nucleoli and mitotic figures. Immunohistochemistry can usually exclude large cell lymphomas, such as high-grade follicular lymphoma and Burkitt lymphoma, when a starry sky pattern is found, as well as Hodgkin Lymphoma; however, the exclusion of diffuse large B-cell lymphoma or marginal zone lymphoma is more difficult. Explorations seeking infectious agents may show Epstein-Barr virus or, rarely, Borrelia burgdorferi involvement. Molecular study occasionally finds a monoclonal B-cell population, but without the subsequent follow-up which would otherwise be worrisome. Despite its somewhat aggressive histologic features, the benignity of this entity must be highlighted to avoid misdiagnosis and complications due to overtreating.

The Rare Face of an Infrequent Lymphoma Diagnosed by an Exquisite Method: Case Report with Review of Literature

AbstractLarge B-cell lymphomas include both the commonly encountered, as well as not so frequent entities. We report a rare case of hepatic intravascular large B-cell lymphoma (IVLBCL). These cases usually pose a major challenge to timely diagnosis due to the limited clinical exposure and nonspecific symptoms; however, timely diagnosis is possible with awareness of this entity and close coordination between radiology and pathology. The patient presented with pain abdomen, fever, edema, hepatomegaly but no lymphadenopathy or cutaneous lesions were identified. Blood investigations revealed pancytopenia, high lactate dehydrogenase (LDH) levels and bone marrow investigations were not helpful. Left-sided portal hypertension, coagulopathy, and hypoalbuminemia raised a clinical suspicion of chronic liver disease with high LDH levels and liver biopsy was challenging in view of very low platelet counts. The uniquely explored transjugular biopsy helped in obtaining liver tissue which showed sinusoidal large atypical lymphoid cells positive for CD20 rendering a diagnosis of IVLBCL. After administration of the R-miniCHOP chemotherapy, there was evident clinical and radiological response. This case highlights the importance of considering transjugular liver biopsy in scenarios where the clinical presentation is unusual. At the same time, a meticulous histological examination is needed to diagnose a rare yet potentially treatable large B cell lymphoma.

SARCOMATOID DIFFUSE LARGE B-CELL LYMPHOMA: A RARE MORPHOLOGICAL VARIANT WITH MULTI-VISCERAL INVOLVEMENT

Diffuse Large B-Cell Lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin's lymphoma (NHL), accounting for 50% of all NHL cases seen at HC-FMUSP. Up to 40-50% of DLBCL cases have extranodal involvement. However, female genital tract involvement is very rare, accounting for less than 0.5% of cases. Spindle/sarcomatoid cell neoplasms usually have mesenchymal histogenesis, however rare cases of aggressive NHL with a spindle-shaped morphological aspect have been recently described, although this variant is still not fully recognized as a specific pathological entity. To describe a rare case of DLBCL with primary uterine cervix involvement, and sarcomatoid morphological pattern, as well as multi-visceral involvement. We intend to highlight the importance of recognizing this entity in the differential diagnosis of spindle-shaped malignant neoplasms. A 51-year-old woman, with no previous comorbidities, sought medical service at the HC-FMUSP due to a vulvovaginal tumor with progressive growth over the last 12 months. Gynecological examination showed an ulcerated tumor in the cervix, extending to the vaginal cavity and exteriorizing through the vulvar introitus. Computed tomography showed a 7 cm tumor mass in the cervix and pathological bone fracture of the L3 vertebra. A biopsy of the uterine cervix showed atypical fusiform cell proliferation, inferring a diagnosis of uterine leiomyosarcoma. However, bone biopsy showed proliferation of large atypical lymphoid cells, suggestive of NHL. Immunohistochemical study of both samples revealed: Ki67+ (80%), CD45+, PAX-5+, diffuse staining for CD20+, BCL-6+, CD79a+, CD30+, with negativity for epithelial and mesenchymal lineage markers. 18-FDG-PETCT revealed involvement of lymph nodes, bones, liver, kidney, thyroid, breasts and bulky in the female genital tract. Diagnosis of DLBCL sarcomatoid variant was established and therapy was scheduled with 6 x R-CHOP, 3 cycles of 3 g/m 2 methotrexate for CNS prophylaxis and uterine cervix radiotherapy depending on residual uptake on PET-CT after chemotherapy. She is currently after 1st. R-CHOP cycle. Sarcomatoid variant of DLBCL is rare and already recognized as a morphological variant of DLBCL NOS by WHO-2016 Classification. The explanation for the occurrence of fusiform neoplastic cells remains unclear, but it is believed that tumor stromal fibrosis can justify deformation of the cell membrane of neoplastic cells, giving the sarcomatoid aspect. Its clinical significance, as well as prognostic impact, have not been established, nor has there been any definition of the need for therapy different from conventional treatment based on anthracyclines (R-CHOP). We described a case of uterine cervix sarcomatoid DLBCL, a rare entity that establishes a differential diagnosis with sarcomas of the female genital tract. Although it is an isolated case, our patient had multivisceral involvement and high-risk IPI, leading us to infer that this morphological variant may be related to greater biological aggressiveness, high tumor burden and poor outcomes, but this needs to be validated with description of other cases and cases series.

Modeling Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia in Transgenic Mice Using Human MYD88L256P Mutated Protein

Lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) is a B-cell disorder resulting from the accumulation of cloncal lymphoplasmacytic cells in the bone marrow (BM) along with excessive secretion of immunoglobulin M paraprotein. Despite recent advances in treatment LPL/WM remains incurable. Generating a refined LPL/WM mouse model that would facilitate studying this disease as well as enable stringent in vivo validation of potential therapeutic approaches has been a long-sought goal for the filed. Interestingly, among the most common mutations identified by recent high-throughput studies there was a single gain of function point mutation in the MYD88 gene, with a predicted non-synonymous amino acid (L265P) change, found in over 91% of patients. Therefore, we hypothesized that generation of transgenic mice overexpressing MYD88L256Pcould recapitulate the human setting of LPL/WM.To overcome problems inherently related to embryonic lethality, we generated MYD88WT and MYD88L256P conditional transgenic mice expressing human proteins. To remove a transcriptional stop cassette and activate MYD88 expression in vivo, we mated the conditional mice with mice expressing Cre recombinase under the control of Activation-Induced Cytidine Deaminase (AID) gene promoter to generate AIDCre/-;MYD88WT/- and AIDCre/-;MYD88L256P/- double-mutant mice. Recombinase activity driven by the AID gene promoter caused removal of the stop cassette and expression of MYD88 in germinal center (GC) and post-GC B cells, the appropriate B-cell compartment from which LPL/WM clones are thought to originate in humans. Young (up to 30 weeks of age) AIDCre/-;MYD88WT/- and AIDCre/-;MYD88L256P/- mice where indistinguishable from AIDCre/- mice as assessed by external physical examination. Moreover, obvious histologic and IHC differences in spleens, lymph nodes, and bone marrows between the mutant genotypes and the AIDCre/- control mice were not found. No clonal bands for the IgH gene, nor M-spikes were detected in Southern blots and serum protein electrophoresis, respectively. However, after 30 weeks of age, and at variable times thereafter, some of the AIDCre/-; MYD88L256P/- aging cohort (n=27) mice developed skin rash and excoriation as well as loss of hair in the submandibular areas. A fraction of AIDCre/-; MYD88L256P/- animals that weren't sacrificed because of the severe dermatitis had enlarged lymph nodes and appeared sick. To assess whether MYD88 transgenic mice develop B-cell lymphomas or major pathologic alterations consistent with the diagnosis of LPL/WM, animals were euthanized at different ages and lymphoid organs were rigorously examined. In spleens and lymph nodes of 8 of the AIDCre/-; MYD88L256P/- animals, a nodular lymphoid infiltrate composed predominantly of small atypical cells varyingly infiltrated with CD138+ plasma cells was observed. Lymphoid cells infiltrated other organs including the BM. Enhanced expression of MYD88 and activation of NF-κB activity within atypical lymphoid nodules in diseased transgenic mice was documented by IHC staining for MYD88 and p65. However, no clonal bands of the IgH gene were detected in Southern blots, suggesting that overexpression of MYD88L256P/- mutant protein in activated B-cells gave rise to a polyclonal lymphoproliferative disorder. Consistently, serum protein electrophoresis analysis showed diffuse, polyclonal increase in γ-globulins. Moreover, stains of peripheral blood smears revealed rouleaux formation suggesting increased concentrations of plasma proteins. In addition, one of AIDCre/-; MYD88L256P/- animals developed a more aggressive monoclonal disease resembling human diffuse large B-cell lymphoma. However, large atypical lymphoid cells in this mouse lacked expression of MYD88 and nuclear p65. All AIDCre/- controls and AIDCre/-; MYD88WT/- mice lacked described phenotypes and were histologically unremarkable.Taken together, these results demonstrate that although MYD88L256P/- alone might not be sufficient to induce a malignant transformation in the mature B-cell compartment, it gave rise to a low-grade mature non-clonal B-cell lymphoproliferative disorder with some of the characteristic futures of LPL/WM. Therefore, the MYD88L256P/- mutation might be necessary but not sufficient for LPL/WM development and must be present with concomitant “second hit” genetic alterations for a neoplasm to develop. DisclosuresTreon:Pharmacyclics: Consultancy, Research Funding.

Two Variants of Follicular Lymphoma Grade 3

Actuality: FL3 is a heterogeneous group of follicular lymphomas. Detailed morphological, immunophenotypic and genetic characteristics of FL3 allow to explain clinical heterogeneity of the disease and to develop differentiated therapeutic approaches.Aim: to characterize clinical, morphological, immunohistochemical (IHC) and genetic features of follicular lymphoma (FL) grade 3 and assess their prognostic value in patients treated with R-CHOP-21.Materials and Methods: In this retrospective and prospective study, 93 primary patients with FL3 (median age 53 years, range 21 - 78 years, f:m=1:1,4) observed in «National Research Center for Hematology» in Moscow, Russian Federation (2001-2016), were included. Morphological and IHC studies of the lymph nodes and corresponding bone marrow trephines obtained prior to therapy have been carried out. Standard cytogenetics or FISH for BCL-2 have been performed.Results: Two variants of the disease were identified: de novo FL (n=22) and transformed FL (tFL) - as a result of histological transformation of low grade follicular lymphoma (n=21). De novo FL3 was characterized by CD10 negativity (86%), MUM1 positivity (90%, with strong monotonous staining), absence of BCL-2 rearrangement (100%), although BCL-2 was found positive in 78% of cases. Bone marrow involvement in cases of de novo FL3 was rare (33%), and in all positive cases - with plenty of large lymphoid cells (centroblasts). tFL3 was positive for CD10 (90%), BCL-2 (95%) and carried rearrangements of BCL-2 in 90%. MUM1 was positive in 76% (heterogeneous staining) and negative in 19%. Bone marrow involvement was documented in 67 %, in most cases with predominance of small lymphoid cells - centrocytes (71%). These data were included in the algorithm for differential diagnosis of two variants of FL3. There was no correlation between the 2 variants of FL3 (de novo or transformed) and grades (3A, 3B or 3A+B) (p=0,11). 26 (60 %) patients from the whole group were treated with R-CHOP-21. The 5-year relapse-free survival of pts with de novo FL3 was 87% compared to 16% for pts with tFL3 (p=0,06), Me=41 months (Figure 1).Conclusion: Two variants of FL3 are described: de novo FL and tFL, which are characterized by different morphological, IHC and genetic features and have various sensitivity to immunochemotherapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

An Unusual Riddle of Thyroid Swelling; Hodgkin’s Lymphoma Masquerading as Riedel’s Thyroiditis

Introduction: Thyroid swellings are one of the most common encountered endocrinological presentations however the prevalence of malignancy is about 4-6.5%. Hodgkin lymphomas usually present as neck swelling in form lymphadenopathy and Hodgkin disease affecting the thyroid gland is extremely rare (1-2.5% of all lymphomas). It usually occurs in middle age and has predilection for female gender. It can pose a diagnostic challenge with the histology of sclerosing fibrosis mimicking Riedel’s thyroiditis; another rare cause of stony hard goitre. Case History: A 39yr old female presented with rapidly enlarging painful thyroid mass. She complained of mild dysphagia but denied to have dyspnoea, dysphonia wheeze or stridor. There was no history of weight loss, B symptoms or any significant past illness. Clinically and biochemically she was euthyroid with normal TSH 0.73mU/l(0.35-3.50), Free thyroxine 13pmol/L (8-21), Free T3 3.9pmol/L (3.8-6.0). Blood count showed mild neutrophilia 8.21 (2-7x109/L). IGG subclasses 1-4 were all with normal limits. Initial Ultrasonography demonstrated 4.6 X 3.6cm U3 thyroid nodule extending retrosternally. FNA x2 was THY. Core biopsy demonstrated dense core of fibrous tissue with crushed aggregates of mature lymphoid cells and mixed neutrophils and histiocytes in keeping with fibro inflammatory process suggestive of Riedel’s thyroiditis. Patient was initiated on Prednisolone 100mg OD by the ENT surgeons after MDT discussion and patient had some symptomatic improvement in pain but no discernible reduction in size. Due to side effects from steroids she was referred to endocrinology department. Tamoxifen 20mg BD was started for symptom management. CTNCAP was organised to rule out lymphoproliferative disorder which was negative barring the known thyroid mass. She had no response to Tamoxifen either hence she underwent surgical resection. Surgical resection deemed very difficult due to mass infiltrating the strap muscles and neck vasculature hence wedge resection of the isthmus was done. Histology now revealed bands of dense fibrous tissue with admixed large lymphoid cells showing enlarged, red nucleoli. Immunohistochemistry of the large atypical lymphoid cells expressed CD30, CD15, MUM1, PAX5, CD20, CD79a and BCL6 and diagnosis was revised to Classic Hodgkin lymphoma, nodular sclerosis subtype. She was then referred to haematologist who initiated ABVD chemotherapy and her latest FDG PET scan shows complete metabolic response with significant reduction in the thyroid mass to 17mm X16 mm. Conclusion: Primary thyroid lymphoma can mimic Riedel’s and other forms of fibrosing thyroiditis. Most lymphomas arise from Hashimoto’s thyroiditis. Stony hard neck swellings are difficult to FNA and even core biopsy may not reveal the diagnosis, hence surgical resection and histological diagnosis should be sought earlier as most lymphomas respond well to chemotherapy.

A Rare Case of Classical Hodgkin Lymphoma of the Thyroid Gland

Background: Hodgkin lymphoma (HL) classically occurs in the lymph nodes and only in about 5% of cases occurs in extra-nodal sites. Primary thyroid lymphomas, most of which are non-Hodgkin lymphomas, comprise less than 5% of all thyroid malignancies. Only a few cases of HL of the thyroid have been reported in the literature, and in most of these cases, fine-needle aspiration biopsy (FNAB) was unreliable for diagnosis. We present a case of classical Hodgkin lymphoma of the thyroid that was falsely negative from both FNAB and core needle biopsy specimens and was diagnosed after surgery.Clinical Case: A 51-year-old female was seen for a rapidly enlarging neck mass associated with progressive dyspnea and dysphagia. Despite being a telemedicine visit due to the COVID-19 pandemic, significant enlargement and deformity of the neck were startling. The patient was clinically and biochemically euthyroid with a TSH of 2.49 mIU/L (0.5-5.0 mIU/L) and normal FT4. She denied a personal or family history of thyroid disease and neck irradiation. Thyroid ultrasound revealed a 5.3 cm hypoechoic, wider than tall nodule with smooth margins in the left lobe, and a 1.9 cm hypoechoic and taller than wide nodule in the right lobe of the thyroid. A CT scan of the neck also revealed a 1.2 cm lymph node in the left lateral aspect of the thyroid. FNAB of the nodules showed Hurthle cells in a background of crushed lymphocytes with occasional large atypical lymphoid cells. Flow cytometry performed on a repeat FNAB specimen revealed no evidence of lymphoma. A repeat CT scan of the neck performed 2 weeks later due to worsening symptoms demonstrated middle mediastinal lymphadenopathy and a large 8x4.7x4.7 cm mass contiguous with the thyroid with a 3.8 cm cystic collection within. The patient was scheduled for an oncology consultation due to the high likelihood of lymphoma but was admitted to another institution with symptoms. She underwent a thyroid core biopsy and flow cytometry, which again failed to reveal her diagnosis. She then underwent left partial thyroidectomy, and pathology demonstrated infiltrates of small lymphocytes with histiocytes, interspersed with clusters of large, irregular, multilobate cells consistent with Reed-Sternberg cells. She was diagnosed with nodular sclerosing variant of classical HL. Chemotherapy was instituted with rapid improvement in symptoms.Clinical Lesson: Primary HL of the thyroid is extremely rare and most often presents as a rapidly enlarging neck mass with or without compressive symptoms. Diagnosis with FNAB is challenging and can be misinterpreted as lymphocytic thyroiditis. In our patient, flow cytometry was performed twice and was falsely negative. The treatment of HL differs entirely from that of other primary thyroid cancers and thyroiditis. Hence, in patients presenting with classic symptoms, a high index of suspicion is needed to make an accurate and prompt diagnosis of HL.

Multiple small tumor formation on both surfaces of the aortic valve cusps in Epstein\u2013Barr virus-associated T/NK-cell lymphoproliferative disease: a case report

A 41-year-old woman presented acute cerebral infarction. Transesophageal echocardiography revealed multiple masses only on both surfaces of the aortic valve cusps. There was no primary lesion outside the heart according to various examinations. After treatment for cerebral infarction, we replaced the aortic valve instead of preservation because the intraoperative histological examination reported that malignancy was highly suspected. Contrary to the rapid frozen section diagnosis, histological and immunohistochemical examinations failed to exhibit malignancy. The tumors were composed of atypical large lymphoid cells and they were assessed to be related to T-/natural killer-cells. Furthermore, Epstein–Barr virus related markers were also positive. Her three-year postoperative course was uneventful without chemotherapy. We report an extremely rare case of Epstein–Barr virus-associated T-/natural killer-cell lymphoproliferative disease which formed multiple small tumors on both surfaces of the aortic valve.

The Transformation of Burnet's Immune Surveillance Cells into Natural Killer Cells and its Circumstances

In 1969 it was very difficult to explain the sudden unexpected appearance of some finely granulated large lymphoid cells that had been hidden in the human blood for over a full century, as they suddenly revealed themselves in our laboratory at M.D. Anderson Hospital, Houston TX. At first, the hematopathologists considered these cells to be of monocytoid (M) derivation

Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype

AbstractAnaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P < .0001), lower serum lactate dehydrogenase level (P = .01), better performance status (P = .03), less frequent extranodal involvement (P = .01), lower international prognostic index (IPI) categories (P = .002), and superior survival (P = .0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56+ cases showed a significantly poor prognosis overall (P = .002) as well as in both ALK-positive and ALK-negative subgroups (P = .02 andP = .04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56+ cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56+ and CD56− groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.

Clinicopathologic Comparison of Plasmablastic Lymphoma Patients According HIV-Status: Peruvian Experience

Background:Plasmablastic lymphoma (PBL) is an aggressive lymphoma associated mainly to HIV infection, although cases in immunocompetent patients are described as well. Objective:To describe the clinicopathologic features and determine the overall survival of lymphoma patients according human immunodeficiency virus (HIV) status in Peruvian patients. Methods:We reviewed the pathology databases of 2 cancer centers and a general hospital from Peru. Forty cases were documented between 2005 and 2020. Categorical variables were compared using Fisher's exact test. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Statistical analysis was based on SPSS Program version 23. All cases were reviewed by two pathologists. Results:32 patients (80%) were HIV-positive. The median age for the whole cohort was 40 years (range, 22-86). The median age for HIV-positive and HIV-negative PBL patients were 37 years (range 22-67 years) and 57 years (range 27-86 years), respectively. The proportion of patients ≥60 years was lower in HIV-positive than in HIV-negative patients (8% and 37%, respectively; p= 0.046). 80% of patients in the whole cohort were female, and 84% and 62% in the HIV-positive and HIV-negative group, respectively. Extra-oral primary sites were the most frequent primary sites in both groups (66% and 88%, respectively). There were no statistically significant differences in Ann Arbor stage, Ki-67 expression, LDH levels, IPI scores, albumin levels, and neutrophil/lymphocyte ratio between HIV-positive and HIV-negative patients. All cases showed large lymphoid cells, of plasmablastic morphology with expression of at least one plasma cell marker (CD138, CD38, MUM1), CD45 positivity, variable expression of EMA, CD79 and CD30 and absence of expression of CD20, CD3, CD68 and LMP1; the proliferative index Ki67 varied between 60 and 90%. A small proportion of patients (18%) did not receive chemotherapy because of poor performance status or a personal decision. DA-EPOCH regimen was used in 52% and 25% of HIV+ and HIV- patients, respectively and CHOP/CHOEP regimen in 48 % and 75%, respectively. The overall response rate was 68% and 57% in HIV+ and HIV- patients with complete response (CR) in 32% and 14%, respectively. In the HIV-positive group, 66% of patients were antiretroviral therapy (ART)-naïve. The median progression-free survival (PFS) was 38 months and 7 months for HIV+ and HIV- patients, and the 1-year PFS was 74% and 0%, respectively. The median overall survival (OS) was 43 months (range 0.2-86.5) in HIV-positive patients and 10 months (range 0.5-19.0 months) in HIV-negative patients and the 1-year OS were 59% y 38%, respectively (p=0.27). Conclusions: PBL is a rare lymphoma, specially, if not related to HIV infection. In this study, 60 years or older was the only variable that showed significant difference. In our cohort, HIV-positive patients had better prognosis than HIV-negative PBL patients. Disclosures No relevant conflicts of interest to declare.

Pediatric-Type Follicular Lymphoma With A Prolonged Clinical Course And Unusual Mutational Profile

Abstract Casestudy: Pediatric-type follicular lymphoma is crucial to differentiate from other subtypes of follicular lymphomas since it carries an excellent prognosis and generally does not require radio- or chemotherapy. We present a 22-year-old male with an 8-year history of a left submandibular mass. Interval imaging studies showed no change in the mass size over time and no other sites of involvement. The patient underwent excision of the mass. Histologic sections showed effacement of nodal architecture with expansile follicles composed of medium sized to large lymphoid cells with blastoid features. Follicles showed abundant tingible body macrophages. Polarization was not seen. Neoplastic follicles were positive for CD20, PAX5, BCL6, CD10, and FOXP1, and negative for BCL2. PD1 positive cells were localized peripherally in the follicles. Clonality was confirmed by flow cytometry (kappa restricted CD10 positive B-cells in a polyclonal background) and by IGH PCR analysis (clonal peaks in FR1 and FR2). Molecular genetic testing showed the following mutations: TNFRSF14 W12* (VAF 14.8%), MAP2K1 F53V (5.7%), EZH2 Y646N (6.9%), ARID1A R1461* (7.1%). BCL2 rearrangement was not detected. MAP2K1 and TNFRSF1 are frequently reported in pediatric-type follicular lymphoma, however in the majority of cases they do not occur together. EZH2 mutation does not typically occur in pediatric-type follicular lymphoma, and is more common in classic adult- onset follicular lymphomas. Despite typical morphologic and clinical features, this patient showed a more complex genetic profile and EZH2 mutation, unusual findings in pediatric-type follicular lymphoma. It is conceivable that a higher genetic complexity has been acquired over time and is related to the long duration of the disease.

Pediatric Patient With Neurological And Leukemic Peripheral Blood Involvement By Small Cell Variant Of ALK- Positive Anaplastic Large Cell Lymphoma (ALCL): Case Study

Abstract Casestudy Anaplastic large cell lymphoma (ALCL), is a T-cell lymphoma typically consisting of large lymphoid cells including characteristic horseshoe- shaped hallmark cells. The rare small cell morphological variant of ALCL may pose a challenge in diagnosis, especially when the initial presentation is unusual. Results Our patient, a 7-year-old girl presented with a headache. A complete blood count showed leukocytosis and anemia. The smear was reported to have segmented neutrophils, reactive lymphocytes, and monocytes. A spinal tap was performed and flow analysis identified a minute aberrant T cell population (0.3% of total), positive for CD3, CD4, bright CD7; negative CD5, CD8 in the CSF sample. The peripheral blood sample was reviewed again; some small- medium atypical lymphocytes, with irregular nuclear contours and cytoplasmic azurophilic granules were noted. Flow immunophenotyping displayed an aberrant T cell population positive for CD45, CD2, CD3, bright CD7, CD4, CD13; negative CD30, TdT CD5, CD8, CD117, CD34; consistent with T cell lymphoma/leukemia. A cell block prepared from peripheral blood sample showed blood with numerous atypical cells with irregular nuclei positive for ALK, CD30, CD3, CD4, CD7; negative CD5 and CD8. A diagnosis of leukemic ALK(+) ALCL was rendered, though classic hallmark cells were difficult to see. A marrow biopsy showed interstitial and sinusoidal pattern of mainly small to medium-sized cells with irregular nuclei. Molecular study revealed ALK gene alteration showing characteristic NPM1-ALK fusion. The patient underwent a bone bone marrow transplantation but recently relapsed with a submandibular lymph hode biopsy showing the presence of many larger ALCL cells. Conclusion Correct clinical diagnosis of the small-cell variant of ALCL is often challenging as the scarce “hallmark cells” are scattered and difficult to recognize. While leukemic peripheral blood involvement is rare in ALCL, an association has been reported with small-cell variants, which may be a potential explanation for the poor prognosis and aggressive nature of small-cell variant ALCL. A meticulous examination of peripheral blood smears, comprehensive immunophenotypic studies, and early bone marrow and lymph node/tissue biopsy are needed to facilitate diagnosis.