Reactive Lymphoid Proliferations Research Articles

Cutaneous Reactive Lymphoid Proliferation Arising in the Setting of Concomitant Antidepressant and Antihypertensive Therapy

Cutaneous Reactive Lymphoid Proliferation Arising in the Setting of Concomitant Antidepressant and Antihypertensive Therapy

Characterization of T-/natural killer cell lymphoproliferative neoplasms associated with systemic, chronic, active Epstein-Barr virus in adults: A report of 5 cases in a Western population.

Because of its low frequency in adult populations and clinical and laboratory overlap with hemophagocytic lymphohistiocytosis and other T-cell lymphomas, T-cell/natural killer (NK) cell systemic, chronic, active Epstein-Barr virus (EBV) (T/NK sCAEBV) infection remains underdiagnosed, preventing critical, prompt therapeutic interventions. We report a 5-case series that included 2 adult patients with T/NK sCAEBV and 3 additional adult patients with T/NK lymphomas with concomitant systemic EBV infection to review these entities' overlapping diagnostic and clinical features. Approximately 95% of the world population has been infected with EBV during their lifetime, and infection is usually asymptomatic, with symptomatic cases eventually resolving spontaneously. A small subset of immunocompetent patients develops CAEBV, a life-threatening complication resulting from EBV-infected T-cell or NK cell neoplastic lymphocytes. The sites of end-organ damage in T/NK sCAEBV demonstrate pathologic findings such as reactive lymphoid proliferations, making the diagnosis difficult to establish, with the only curative option being an allogeneic hematopoietic stem cell transplant. This diagnosis is most prevalent in Asia, with few cases reported in Western countries. Adult age is an independent risk factor for poor outcomes, and most cases are diagnosed in pediatric populations.

Lymphomas with plasmablastic features: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Lymphomas with plasmablastic features are a heterogeneous group of aggressive and mostly uncommon neoplasms of varied aetiologies, presenting in immunocompetent individuals as well as in immunodeficiency, associated with EBV and Kaposi sarcoma virus infections, and some as progression from indolent B-cell lymphomas. They show overlapping diagnostic features and pose a differential diagnosis with other aggressive B-cell lymphomas that can downregulate the B-cell expression programme. The spectrum of rare reactive proliferations and all lymphomas defined by plasmablastic features, together with an expanding range of poorly characterised, uncommon conditions at the interface between reactive lymphoid proliferations and neoplasia submitted to the session V of the 20th European Association for Haematopathology/Society for Hematopathology lymphoma workshop are summarised and discussed in this paper.

Tissue-Specific microRNA Expression Profiling to Derive Novel Biomarkers for the Diagnosis and Subtyping of Small B-Cell Lymphomas.

Accurate diagnosis of the most common histological subtypes of small B-cell lymphomas is challenging due to overlapping morphological features and limitations of ancillary testing, which involves a large number of immunostains and molecular investigations. In addition, a common diagnostic challenge is to distinguish reactive lymphoid hyperplasia that do not require additional stains from such lymphomas that need ancillary investigations. We investigated if tissue-specific microRNA (miRNA) expression may provide potential biomarkers to improve the pathology diagnostic workflow. This study seeks to distinguish reactive lymphoid proliferation (RL) from small B-cell lymphomas, and to further distinguish the four main subtypes of small B-cell lymphomas. Two datasets were included: a discovery cohort (n = 100) to screen for differentially expressed miRNAs and a validation cohort (n = 282) to develop classification models. The models were evaluated for accuracy in subtype prediction. MiRNA gene set enrichment was also performed to identify differentially regulated pathways. 306 miRNAs were detected and quantified, resulting in 90-miRNA classification models from which smaller panels of miRNAs biomarkers with good accuracy were derived. Bioinformatic analysis revealed the upregulation of known and other potentially relevant signaling pathways in such lymphomas. In conclusion, this study suggests that miRNA expression profiling may serve as a promising tool to aid the diagnosis of common lymphoid lesions.

Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Hematolymphoid Proliferations and Neoplasia.

In the 5th edition of the World Health Organization (WHO) Classification of Head and Neck Tumours, the discussion of hematolymphoid proliferations is substantially reorganized and expanded in comparison to the prior edition. The 5th edition includes, in addition to hematolymphoid neoplasms, reactive lymphoid proliferations. Much more information on hematolymphoid proliferations that commonly affect cervical lymph nodes, in addition to those affecting extranodal sites in the head and neck, is included. For the first time, there are dedicated sections on multiple entities, including recently described lymphoproliferative disorders such as EBV+ mucocutaneous ulcer and pediatric-type follicular lymphoma, and several types of histiocytic neoplasms. Tremendous advances have been made in understanding the genetic features that underlie the pathogenesis of hematolymphoid neoplasms, and these have been incorporated into the WHO Classification.

Use of Ultrasensitive RNA In Situ Hybridization for Determining Clonality in Cutaneous B-Cell Lymphomas and Lymphoid Hyperplasia Decreases Subsequent Use of Molecular Testing and Is Cost-effective.

Primary cutaneous B-cell lymphomas (PCBCLs) are diagnostically challenging entities due to significant overlap in clinical and morphologic features with reactive lymphoid proliferations. Traditional methods for evaluating clonality such as immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) are limited by low sensitivity, which leads to additional costly and time-consuming molecular clonality assays. More recent technology has introduced ultrasensitive bright-field RNA in situ hybridization (BRISH) to the field, which can detect single molecules of light-chain mRNA. The current study evaluated 274 cases of PCBCL in addition to atypical and reactive lymphoid infiltrates, with CISH or BRISH performed on 180 (65.7%). CISH was performed on 105 (58.3%), and BRISH was performed on 75 (41.7%). Significantly fewer immunoglobulin heavy-chain (IGH) rearrangement studies were performed on cases that were evaluated with BRISH as compared with CISH (P=0.02). Subgroup analysis demonstrated that cases with restriction by BRISH were significantly less likely to have subsequent IGH studies performed (P=0.01). The expected costs of cases using CISH versus BRISH were $1053.89 versus $810.32 to the patient and $245.63 versus $225.23 to the laboratory. The use of ultrasensitive BRISH to evaluate clonality in PCBCL reduced the use of IGH rearrangement studies when compared with CISH. In particular, cases with light-chain restriction by BRISH did not result in confirmatory molecular testing. Despite slightly higher costs to the laboratory to perform BRISH, routine use of this methodology can result in cost savings to both the patient and laboratory by decreasing the use of expensive molecular methods.

B CELL LYMPHOMA PRESENTING AS A CYSTIC LUNG DISEASE

TOPIC: Lung Cancer TYPE: Fellow Case Reports INTRODUCTION: Cystic lung airspaces can be seen in a multitude of diseases including lymphangioleiomyomatosis, Langerhan cell histiocytosis, Birt-Hogg-Dube syndrome, cystic metastases, or even postinfectious pneumatoceles. Lymphoma, however, is not often included in the differential diagnosis. We describe a rare presentation of B cell lymphoma presenting as a cystic lung disease. CASE PRESENTATION: Forty five year old female with a past medical history of diabetes mellitus and hypertension was originally referred to us for a lung biopsy. Patient had worsening shortness of breath for 1 year. She had a computed tomography of the chest at another facility which showed extensive cystic spaces in the lungs, suspicious for lymphangiomyomatosis. Patient was evaluated by a pulmonologist as an outpatient and had a bronchoscopy with biopsy. After receiving inconclusive results, she was given a course of antibiotics and had relief of her symptoms for some time. Months later the patient had an episode of severe coughing which prompted a visit to a hospital within our system where she had another computed tomography of the chest with contrast revealing the same diffuse cystic disease that was worse at the bases. She was subsequently referred to us and underwent video-assisted thoracic surgery with right upper, middle, and lower lobe biopsies. Pathology of the right middle lobe was revealed diffuse large B-cell lymphoma. Cystic change was seen in all of the biopsies. DISCUSSION: Lymphoma is one of the great masqueraders in medicine. Because of this, it should be included in the differential diagnosis for patients such as this with multiple cystic airspaces. Primary pulmonary extranodal lymphomas are rare, accounting for 0.4% of all lymphomas, and only 15-20% of these are high grade. These lymphomas are usually either mucosa-associated (MALT) or bronchus-associated lymphoid tissue (BALT) lymphomas. Presentations vary but are most often found as solitary nodules or masses and may be found incidentally. With more diffuse disease, other symptoms like shortness of breath, cough, chest pain, or even hemoptysis may arise. There is an association between immunosuppression and pulmonary lymphomas, as well with human immunodeficiency virus (HIV) infection and inflammatory conditions like rheumatoid arthritis and Sjogren disease. Diagnosis requires surgical biopsy because a bronchoalveolar lavage or fine needle biopsy may show lymphoma cell infiltration but cannot exclude other differential diagnoses such as reactive lymphoid proliferation, or lymphoid interstitial pneumonia. CONCLUSIONS: Lymphoma is one of the great masqueraders in medicine and can present in many different ways. Because of this, it should be included in the differential diagnosis in patients such as this with multiple cystic airspaces of the lungs. Diagnosis requires a surgical biopsy which should be included in these cases. REFERENCE #1: Girard, N., & Cadranel, J. (n.d.). Rare Primary Lung Tumors. In Murray and Nadel's Textbook of Respiratory Medicine (6th ed., pp. 965-980). Elsevier. REFERENCE #2: Hagga, John. "Nonneoplastic Parenchymal Lung Disease." CT and MRI of the whole body, 6th ed., Elsevier, 2017, pp. 928–983. REFERENCE #3: Myers, J. L. (2018). Lung. In Rosai and Ackerman's Surgical Pathology (11th ed., pp. 372-443). Elsevier. DISCLOSURES: no disclosure on file for Bishoy Hanna; No relevant relationships by Diego Marin, source=Web Response no disclosure on file for Christina Migliore Patel; no disclosure on file for Xinlai Sun

Epstein-Barr Virus Positive B-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract.

Simple SummaryEpstein-Barr virus (EBV) contributes to the reactive and neoplastic lymphoid proliferation of B-, T-, and NK-cell lineages, which represent a vast clinicopathological spectrum ranging from indolent, self-limited disease to aggressive lymphomas. EBV-positive B-cell lymphoproliferative disorder (EBV+ B-LPD) is the most common of these diseases, accounting for 3% to 15% of diffuse large B-cell lymphomas. The spectrum of EBV+ B-LPD is expanding with advances in understanding immunosenescence and iatrogenic immunodeficiency in the era of immune-oncology. We review EBV+ B-LPD affecting the gastrointestinal tract with a focus on the PD-L1 expression in tumor and non-malignant immune cells to better understand this peculiar disease.Epstein-Barr virus positive B-cell lymphoproliferative disorder (EBV+ B-LPD) encompasses a broad clinicopathological spectrum and distinct clinical behavior that relatively favors the gastrointestinal (GI) tract. In this review, we provide an update on the clinicopathological features and biological behavior of EBV-positive mucocutaneous ulcer (EBVMCU) and primary EBV+ diffuse large B-cell lymphoma (DLBCL) of the GI tract. EBVMCU is a newly recognized entity but well known as an indolent and self-limited EBV+ B-LPD occurring in various immunodeficiencies. In contrast, EBV+ DLBCL constitutes the largest group of EBV+ B-LPDs and is regarded as an aggressive neoplasm. These two distinct diseases have historically been distinguished in the reappraisal of age-related EBV-associated B-LPDs but are challenging in routine practice regarding their differential diagnostic and therapeutic approaches. An increasing number of reports indicate that they are epidemiologically prevalent beyond western and eastern countries, but their comprehensive analysis is still limited. We also describe the PD-L1 positivity of tumorous large cells and non-malignant immune cells, which is relevant for the prognostic delineation among patients with primary DLBCL of the GI tract with and without EBV on tumor cells.

Hiperplasia linfoide folicular oral: clinicopatológico de uma série de casos

ABSTRACT Follicular lymphoid hyperplasia (FLH) is a reactive lymphoid proliferation that can simulates lymphomas, both clinically and histologically. The aim of the present study was to investigate the clinical, morphological and immunohistochemical characteristics of a series of FLH cases of the oral cavity, and discuss important diagnostic aspects and differential diagnosis concerning follicular lymphomas. A retrospective analysis of the records of a database comprising 38 years revealed nine cases diagnosed as FLH of the oral cavity. Patient age ranged from 8 to 44 years. Most lesions were located in the buccal mucosa and the presence of a painless nodule was the most common clinical finding. Histopathological analysis revealed the proliferation of lymphoid cells arranged in a follicular pattern, presenting primary and secondary follicles with a germinal center and mantle zone, with evidence of macrophages containing apoptotic bodies in their interior, as well as evidence of typical mitosis figures. Interfollicular region, lymphocytes, macrophages and epimioepithelial islands were observed. Immunohistochemical analysis revealed positivity of the lymphoid follicles for CD20, CD68, CD3 and B-cell lymphoma 2 (Bcl-2). The clinical presentation of FLH and histopathological evidence of lymphatic follicles presenting indistinct germinal centers with poorly defined mantle zone may represent a problem due to theresemblance to follicular lymphoma.

Spleen: Development, anatomy and reactive lymphoid proliferations.

The unique architecture of the spleen enables it to play a key role in the interactions between the circulatory, reticuloendothelial and immune systems. Response to circulating antigens in the setting of infection, autoimmune disease or other conditions may result in a range of benign lymphoid proliferations. Moreover, patients with underlying immune deficiency may also show abnormal lymphoid proliferations within the spleen. This review will highlight the histologic, immunophenotypic and clinical features of reactive lymphoid proliferations to aid in their recognition and provide a context for understanding their development in relation to normal splenic structure and function.

Primary Cutaneous Composite Lymphomas.

Composite lymphomas have been defined as 2 distinct subtypes of lymphoma occurring at a single anatomic site. Composite lymphomas limited to the skin are a rare occurrence and pose a unique challenge. Many reported cases within the skin are combined B-cell and T-cell lymphomas, typically mycosis fungoides and a low-grade B-cell lymphoma. These cases are challenging to recognize because lymphoid infiltrates within the skin often include a mixed population of B cells and T cells. In particular, reactive lymphoid proliferations (pseudolymphomas), primary cutaneous low-grade B-cell lymphomas, and primary cutaneous CD4+ T-cell lymphoproliferative disorder may show nearly equal numbers of B cells and T cells. In order to exclude these possibilities, overwhelming evidence in support of each lymphoma is helpful, including abnormal architecture, cytology, and immunophenotype, as well as molecular genetic evidence of clonality.

Adult T cell leukemia/lymphoma complicated by proliferation of large B cells: a diagnostic dilemma

Peripheral T cell lymphomas are clinically and pathologically complex and generally associated with overall poor prognosis and aggressive clinical course. In recent years, there is a greater recognition of abnormal B cell expansion as a component of T cell lymphomas especially those derived from follicular helper T cells. Most of these B cells are EBV positive and show a wide range of morphology which includes large mononuclear cells and Hodgkin-like cells. The number of the abnormal B cells can also vary. It is possible to misdiagnose this entity as a B cell lymphoma, Hodgkin lymphoma, composite lymphoma, or reactive lymphoid proliferation based on the number and morphology of the proliferating B cells. Herein, we report the case of an 82-year-old woman who presented with cervical lymphadenopathy, excision biopsy of which showed diffusely arranged atypical small- to medium-sized cells with irregular nuclei admixed with large number of immunoblast-like large cells. Immunophenotyping showed the small- to medium-sized cells to be CD20 negative, CD3 positive, and CD5 positive and showed downregulation of CD7. These cells were CD25 positive and showed a high MIB 1 labelling index. The large cells were CD20 positive and CD30 positive and showed EBV-encoded small nuclear RNA (EBER) positivity. Serum HTLV-1 estimation was positive. Molecular studies showed TCR gene rearrangement and a polyclonal population of B cells. Based on morphology, immunoprofile, and molecular studies, a diagnosis of adult T cell leukemia/lymphoma complicated by proliferation of large B cells was given. The presence of large B cell proliferation in adult T cell leukemia/lymphoma is an exceptionally rare phenomenon.

Pulmonary Nodular Lymphoid Hyperplasia: A Rare Case Mimicking Malignancy

Pulmonary nodular lymphoid hyperplasia (PNLH) is a reactive lymphoid proliferation manifesting as multiple solitary nodules or localized infiltrates in the lungs. It is a type of benign lymphoproliferative disease that can affect the lungs. We present the case of a 41-year-old female patient with respiratory symptoms such as productive cough, left chest pain, and dyspnea. Imaging findings revealed two lesions with lobulated contour in the left upper lobe apicoposterior segment and left lower lobe superior segment. After examining the minimally invasive diagnostic methods, this rare PNLH case mimicking malignancy was both diagnosed and treated by surgery. Further studies including more patients and longer follow-ups are needed for this rare disease.

Epstein-Barr Virus (EBV) associated reactive and indeterminate lymphoid proliferations in the lymph node.

Epstein-Barr Virus (EBV) associated reactive and indeterminate lymphoid proliferations in the lymph node.

Potential mechanism and prognostic value of promoter methylation of PRDM1 gene in diffuse large B cell lymphoma

Objective: To investigate PRDM1 gene methylation status, immune classification and their prognostic significance in diffuse large B cell lymphoma (DLBCL). Methods: Immunohistochemical (IHC) staining for CD20, CD10, bcl-2, bcl-6, PRDM1/Blimp-1 and MUM1 was carried out in 100 cases of DLBCL specimens and 20 reactive lymphoid proliferation samples. All patients were classified into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtype according to Hans' algorithmin. PRDM1 gene methylation was detected by methylation-specific PCR (MSP) and its relationship with clinicopathologic parameters was analyzed. OCI-Ly1 (GCB type) and OCI-Ly3 (ABC type) cell lines were transfected by Small interfering RNA(siRNA) with cationic lipid reagent transfection mediated, and the PRDM1/Blimp-1 expression in before and after transfected cell lines were detected with reverse transcription-PCR and Western blot methods. The relationship between PRDM1 gene methylation, clinicopathologic parameter and survival was analyzed using one-way analysis of variance. Results: One hundred patients were classified into 73 (73%) cases of GCB subtypes and 27 (27%) cases of ABC. PRDM1/Blimp-1 was expressed in 21 DLBCL and highly expressed in 20 reactive lymphoid proliferation. PRDM1 gene methylation was detected in 23% (23/100) of DLBCL, while no methylation was detected in all 20 reactive lymphoid proliferation. The difference of the PRDM1 methylation status between DLBCL and the control samples was statistically significant (P=0.004). However, there was no significant correlation between the PRDM1 gene methylation and clinicopathologic parameters (P>0.05). Reverse transcription-PCR and Western blot showed that PRDM1 gene expression was reduced in siRNA-induced group compared with blank control group and negative control group. One-way analysis of variance revealed that aged ≥60 years, performance status score above 3, and the presence of general symptoms were associated with significantly lower overall survival rate. Conclusions: PRDM1 gene silencing with aberrant CpG methylation is probably one of the critical events in the oncogenesis of DLBCL. This may have important implications as a candidate marker for diagnosis and targeted gene therapy. Meanwhile in vitro siRNA transfected OCI-Ly1 and OCI-Ly3 cell lines confirm that PRDM1 gene is a suppressor gene in DLBCL and may represent a novel therapeutic target.

Cutaneous Pseudolymphomas

The term cutaneous pseudolymphoma refers to benign reactive lymphoid proliferations in the skin that simulate cutaneous lymphomas. It is a purely descriptive term that encompasses various reactive conditions with a varied etiology, pathogenesis, clinical presentation, histology, and behavior. We present a review of the different types of cutaneous pseudolymphoma. To reach a correct diagnosis, it is necessary to contrast clinical, histologic, immunophenotypic, and molecular findings. Even with these data, in some cases only the clinical course will confirm the diagnosis, making follow-up essential.

Pseudolinfomas cutáneos

The term cutaneous pseudolymphoma refers to benign reactive lymphoid proliferations in the skin that simulate cutaneous lymphomas. It is a purely descriptive term that encompasses various reactive conditions with a varied etiology, pathogenesis, clinical presentation, histology, and behavior. We present a review of the different types of cutaneous pseudolymphoma. To reach a correct diagnosis, it is necessary to contrast clinical, histologic, immunophenotypic, and molecular findings. Even with these data, in some cases only the clinical course will confirm the diagnosis, making follow-up essential.

Evaluation of pathologic lesions in superficial lymph node biopsies

Introduction: Lymphadenopathy can be due to any disease process involving lymph nodes. Enlargement of lymph node is a very common clinical symptom seen in outpatient department of any hospital. Lymphadenopathy can occur at any age group and at any site of the body. Detail clinical history for signs and symptoms, size of lymph nodes, presence of generalized lymphadenopathy, and hepatosplenomegaly help to arrive at provisional diagnosis. Histopathological examination of the lymph node biopsies is a gold standard test in the distinction between reactive and malignant lymphoid proliferations as well as for detailed subtyping of lymphomas. Aim: The aim of present study is to analyze pathological spectrum of various neoplastic and non-neoplastic lesions affecting superficial lymph nodes in the neck, axilla, inguinal region and correlation with clinical findings. Materials and Methods: The present study was a retrospective study conducted in the department of Pathology, at Chalmeda Anand Rao Institute of Medical Sciences, Bommakal Karimnagar,during the period from february 2014 to march 2015. Lymph node biopsies of all patients of both sexes and all age groups were included. Total 47 lymph node biopsies were selected for histopathological evaluation which constituted the study material. Among these 25 were from males and 22 were from females with male to female ratio being 1.2:1. The age of the patients ranged from 3 to 71 years with a mean age of 40-49 years. Results: Out of total 47 cases, 15(31.9%) cases were tuberculous lymphadenitis ,13 cases (27.6%) were malignant lymphoma while metastasis was found in 10(21.2%) cases, reactive hyperplasia in 5(10.6%) cases, suppurative lymphadenitis in 2(4.2%) cases, castleman disease and kikuchi disease, the least common condition was seen in only one case(2.1%) each. Cervical lymph nodes were most commonly biopsied group of lymph nodes in our study. Conclusion: Tuberculosis was the most common cause of lymphadenopathy, followed by malignant lymphoma and the cervical group of lymph nodes was most frequently affected.

The comparison of the pathological data of oropharyngeal masses between HIV and non-HIV patients

Conclusion: Although this study did not show higher risk of oropharyngeal malignancy in HIV patients overall, they still had much higher prevalence of NHL as well as HL than HIV negative patients. Presence of cervical lymphadenopathy is unreliable in differentiating malignant oropharyngeal tumours from benign lymphoid hyperplasia in HIV patients.Objectives: The aim of this study was to compare the histology of oropharyngeal masses between HIV positive and negative patients.Methods: A retrospective review of 119 patients who underwent oropharyngeal biopsies in a tertiary institution between 2007–2014 and whose HIV status was known (HIV positives =47; negatives =72).Results: Malignancies occurred in 63.8% of HIV patients and 65% of the negative group (p = 0.87). While non-Hodgkin’s lymphoma (NHL), squamous cell carcinoma (SCC), and Hodgkin’s lymphoma (HL) constituted 40%, 27%, and 17% of malignancies in HIV patients, respectively; in the HIV-negative group, it was 53%, 13%, and 2% for SCC, NHL, and HL, respectively (p = 0.039, 0.017, and 0.035, respectively). Reactive lymphoid proliferation accounted for 82.4% of the benign masses in the HIV positive group. Malignant tumours were recorded more in younger patient in the HIV positive than the negative group (p = 0.001).

Clonality Testing in Veterinary Medicine

The accurate distinction of reactive and neoplastic lymphoid proliferations can present challenges. Given the different prognoses and treatment strategies, a correct diagnosis is crucial. Molecular clonality assays assess rearranged lymphocyte antigen receptor gene diversity and can help differentiate reactive from neoplastic lymphoid proliferations. Molecular clonality assays are commonly used to assess atypical, mixed, or mature lymphoid proliferations; small tissue fragments that lack architecture; and fluid samples. In addition, clonality testing can be utilized to track neoplastic clones over time or across anatomic sites. Molecular clonality assays are not stand-alone tests but useful adjuncts that follow clinical, morphologic, and immunophenotypic assessment. Even though clonality testing provides valuable information in a variety of situations, the complexities and pitfalls of this method, as well as its dependency on the experience of the interpreter, are often understated. In addition, a lack of standardized terminology, laboratory practices, and interpretational guidelines hinders the reproducibility of clonality testing across laboratories in veterinary medicine. The objectives of this review are twofold. First, the review is intended to familiarize the diagnostic pathologist or interested clinician with the concepts, potential pitfalls, and limitations of clonality testing. Second, the review strives to provide a basis for future harmonization of clonality testing in veterinary medicine by providing diagnostic guidelines.