Benign Lymphoid Proliferations Research Articles

Lymphoid Interstitial Pneumonia (LIP) Revisited: A Critical Reappraisal of the Histologic Spectrum of "Radiologic" and "Pathologic" LIP in the Context of Diffuse Benign Lymphoid Proliferations of the Lung.

The use of lymphoid interstitial pneumonia (LIP) as a diagnostic term has changed considerably since its introduction. Utilizing a multi-institutional collection of 201 cases from the last 20 years that demonstrate features associated with the LIP rubric, we compared cases meeting strict histologic criteria of LIP per American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus ("pathologic LIP"; n=62) with cystic cases fulfilling radiologic ATS/ERS criteria ("radiologic LIP"; n=33) and with other diffuse benign lymphoid proliferations. "Pathologic LIP" was associated with immune dysregulation including autoimmune disorders and immune deficiency, whereas "radiologic LIP" was only seen with autoimmune disorders. No case of idiopathic LIP was found. On histology, "pathologic LIP" represented a subgroup of 70% (62/88) of cases with the distinctive pattern of diffuse expansile lymphoid infiltrates. In contrast, "radiologic LIP" demonstrated a broad spectrum of inflammatory patterns, airway-centered inflammation being most common (52%; 17/33). Only 5 cases with radiologic cysts also met consensus ATS/ERS criteria for "pathologic LIP." Overall, broad overlap was observed with the remaining study cases that failed to meet consensus criteria for "radiologic LIP" and/or "pathologic LIP." These data raise concerns about the practical use of the term LIP as currently defined. What radiologists and pathologist encounter as LIP differs remarkably, but neither "radiologic LIP" nor "pathologic LIP" present with sufficiently distinct findings to delineate such cases from other patterns of diffuse benign lymphoid proliferations. As a result of this study, we believe LIP should be abandoned as a pathologic and radiologic diagnosis.

Complicated ways of diagnosing common variable immune deficiency (case report)

Common variable immunodeficiency (CVID) is one of the most frequent forms of primary immunodeficiencies with predominant antibody deficiency. Unlike most other primary immunodeficiencies, this variant often manifests in adults thus creating certain difficulties in its detection. Manifestations of common variable immune deficiency are very diverse: infectious syndrome (respiratory tract infections, septic arthritis), diarrheal clinical pattern of both infectious and non-infectious genesis, autoimmune syndrome (autoimmune cytopenias, systemic rheumatic diseases), lymphoproliferative syndrome (benign lymphoid proliferation, lymphomas), interstitial lung disease and sarcoidosis-like granulomatous changes are quite common. Due to the lack of a distinct clinical pattern, the common variable immunodeficiency is often diagnosed too late. Such patients are observed for a long time by various specialists, and the absence of pathogenetic therapy (intravenous immunoglobulins) leads to steady progression of the disease and, often, to lethal outcome. The article presents a clinical observation illustrating the difficulties in making this diagnosis. A woman hospitalized with pneumonia presented with a mass in colonic submucosa. After excluding tuberculosis and lymphoma, a diagnosis of colon lipoma was made on the basis of histological examination. A few years later, the patients submandibular lymph nodes were periodically enlarged. Upon repeated histological examination, the diagnosis of granulomatous necrotizing lymphadenitis was established, the patient was referred to a rheumatologist to rule out systemic vasculitis. This diagnosis was not confirmed, but further examination revealed a sharp decrease in the gamma fraction of serum proteins. Therefore, an immunologists counseling was recommended to rule out immunodeficiency. The following blood serum analysis revealed an extremely low IgG and IgM content, with absence of detectable immunoglobulin A. On the basis of these findings, the diagnosis of common variable immune deficiency was made for the first time. Replacement therapy with high-dose intravenous immunoglobulins with control of pre-transfusion Ig levels was recommended, with further transition to a supporting treatment schedule. Hence, one may state that general practitioners are still poorly aware of primary immunodeficiencies, especially if non-infectious manifestations dominating in the clinical pattern. Routine analysis of total protein content and protein fractions can provide information that allows to suspect deficiency of antibodies and, therefore, to assess contents of distinct serum immunoglobulins in order to confirm CVID diagnosis.

The clinicopathologic features and differential diagnosis of ocular Kimura disease and epithelioid hemangioma

Objective: To investigate the clinicopathologic features and differential diagnosis of ocular Kimura disease (KD) and epithelioid hemangioma. Methods: It was a retrospective case series study. The data of 10 patients with ocular KD and 3 patients with ocular epithelioid hemangioma from the Pathology Department of Eye & ENT Hospital of Fudan University from January 2010 to December 2019 were retrospectively analyzed, including clinical manifestations, morphology and immunophenotypes. Results: Among patients with ocular KD, there were 9 males and 1 female with an age from 7 to 75 years (mean, 30 years). There were 6 unilateral cases and 4 bilateral cases. The disease mainly involved the orbit in 3 patients, the lacrimal gland in 5 patients and the eyelid in 2 patients. The ophthalmic presentation included a palpable periorbital or eyelid mass with eyelid swelling and ptosis, proptosis and displacement of the eyeball, and ocular dysmotility. Three patients had a history of lymphadenopathy. The disease course ranged from 6 months to 7 years (mean, 34 months). All the patients had elevated peripheral blood eosinophilia. Three patients of ocular epithelioid hemangioma were all males with age from 25 to 60 years old. They were all unilateral cases with 1 right eye and 2 left eyes. The disease respectively involved eyelid and orbit, the eyebrow skin and the inner canthus skin. They presented with eyelid swelling, orbital mass or subcutaneous nodule for 5 months to 2 years. All patients (11 eyes) with KD underwent incisional or excisional biopsy. The histopathology revealed follicular hyperplasia of lymphoid tissue with active germinal centers in orbital fibroadipose tissue. There were massive interfollicular eosinophils with eosinophilic microabscesses. Some swelling endothelial cells of proliferating vessels were seen. All the 3 patients (3 eyes) with ocular epithelioid hemangioma underwent excision of the lesions. Histopathological examination showed proliferation of small and medium blood vessels. The vessels were lined by endothelial cells with abundant eosinophilic cytoplasm which protruded into the lumen. The endothelial cells were positive for CD31, factor Ⅷ-related antigen and E26 transformation-specific related gene immunohistochemically. There was a moderate amount of lymphocytes, plasma cells and eosinophils surrounding blood vessels without eosinophilic microabscess. Conclusions: Both ocular KD and epithelioid hemangioma are more commonly seen in males and share the common histopathological features of vascular proliferation, swelling endothelial cells and eosinophilic infiltration. KD is an allergic benign lymphoid tissue proliferation characteristic of massive eosinophilic infiltration, whereas epithelioid hemangioma is a benign neoplasm of blood vessels with plump and epithelioid endothelial cells. (Chin J Ophthalmol, 2021, 57: 689-695).

Next-Generation Sequencing–Based Clonality Assessment of Ig Gene Rearrangements: A Multicenter Validation Study by EuroClonality-NGS

Ig gene (IG) clonality analysis has an important role in the distinction of benign and malignant B-cell lymphoid proliferations and is mostly performed with the conventional EuroClonality/BIOMED-2 multiplex PCR protocol and GeneScan fragment size analysis. Recently, the EuroClonality-NGS Working Group developed a method for next-generation sequencing (NGS)-based IG clonality analysis. Herein, we report the results of an international multicenter biological validation of this novel method compared with the gold standard EuroClonality/BIOMED-2 protocol, based on 209 specimens of reactive and neoplastic lymphoproliferations. NGS-based IG clonality analysis showed a high interlaboratory concordance (99%) and high concordance with conventional clonality analysis (98%) for the molecular conclusion. Detailed analysis of the individual IG heavy chain and kappa light chain targets showed that NGS-based clonality analysis was more often able to detect a clonal rearrangement or yield an interpretable result. NGS-based and conventional clonality analysis detected a clone in 96% and 95% of B-cell neoplasms, respectively, and all but one of the reactive cases were scored polyclonal. We conclude that NGS-based IG clonality analysis performs comparable to conventional clonality analysis. We provide critical parameters for interpretation and discuss a first step toward a quantitative scoring approach for NGS clonality results. Considering the advantages of NGS-based clonality analysis, including its high sensitivity and possibilities for accurate clonal comparison, this supports implementation in diagnostic practice.

Markers of Follicular Helper T Cells Are Occasionally Expressed in T-Cell or Histiocyte-Rich Large B-Cell Lymphoma, Classic Hodgkin Lymphoma, and Atypical Paracortical HyperplasiaA Diagnostic Pitfall For T-Cell Lymphomas of T Follicular Helper Origin.

Follicular helper T cell (TFH) markers are expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma of the TFH phenotype (PTCL-TFH). However, differential expression and coexpression of these markers in benign and other malignant lymphoid proliferations have not been well studied. We performed programmed death-1 (PD-1), C-X-C motif chemokine ligand 13 (CXCL13), inducible costimulator (ICOS), CD10, and B-cell lymphoma 6 protein (BCL-6) immunohistochemistry on AITL, PTCL not otherwise specified (PTCL-NOS), PTCL-TFH, T-cell or histiocyte-rich large B-cell lymphoma (THRLBCL), classic Hodgkin lymphoma (CHL), atypical paracortical hyperplasia (PCH), progressive transformation of germinal centers (PTGC), and reactive follicular hyperplasia (RFH). CXCL13 and ICOS were more sensitive but less specific for AITL than PD-1, CD10, and BCL-6. Moreover, 74% of AITL (none of PTCL-NOS or PTCL-TFH) coexpressed more than 2 TFH markers. In background T cells of THRLBCL, 70% of cases coexpressed more than 1 marker. The background T cells of CHL expressed all TFH markers except CD10 in all cases. In addition, 13% of PCH cases coexpressed more than 1 marker. In RFH and PTGC, all markers were expressed mainly in germinal centers with rare extrafollicular staining. AITL, PTCL-NOS, and PTCL-TFH show differential expression of TFH markers. AITL frequently coexpresses more than 2 TFH markers. TFH markers can be expressed in PCH and in background T cells of THRLBCL and CHL. Consequently, caution should be used before a diagnosis of AITL is established, particularly with limited samples.

MULTIFOCAL PULMONARY NODULAR HYPERPLASIA IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare lympho-proliferative disorder characterized by benign polyclonal lymphoid proliferation. We describe a case of a 44-year-old woman with biopsy proven multifocal pulmonary nodular lymphoid hyperplasia in the setting of SLE. CASE PRESENTATION: 44-year-old woman presented to the emergency room with complaints of intermittent pleuritic chest pain and exertional dyspnea for 3 months. Review of systems was positive for joint pains and morning stiffness. Physical examination was remarkable for tenderness and swelling at proximal interphalangeal joints. Cardiac work up including electrocardiogram, troponin levels and echocardiogram was unremarkable. CT scan of chest with contrast showed numerous bilateral cavitary ground glass opacities measuring about 1-2 cm in size. Transbronchial biopsy was non-diagnostic. A subsequent video-assisted thoracoscopic surgical biopsy revealed nodular lymphoid hyperplasia. Specimen was negative for malignancy, granulomatous disease or vasculitis. Lymphoma was also ruled out by flow cytometry. AFB, fungal and bacterial stains and cultures were negative. Hepatitis panel and HIV testing was negative. Rheumatologic work up showed negative rheumatoid factor and positive ANA, anti-SSA, anti-dsDNA Ab, anti smith and anti-U1-RNP antibodies. Inflammatory markers, ESR and CRP, were elevated. She was evaluated by rheumatology and further history revealed presence of alopecia and nasal sores in addition to serositis (pleuritis) and arthritis. Her clinical picture and serologies met the diagnostic criteria for SLE. DISCUSSION: Pulmonary lymphoid nodular hyperplasia is a rare benign lymphoproliferative disease. It is relatively more common in women and often an incidental finding on imaging. Most patients are asymptomatic, however symptoms such as cough, chest pain or dyspnea can be present. Diagnosis is made by surgical biopsy. It is essential to rule out malignancy, particularly mucosal associated lymphoid tissue lymphoma and infectious etiologies such as bacterial or fungal pulmonary infections. So far PNLH has been described in patients with Sjogren’s disease, without conclusive association. Most common pulmonary manifestation in SLE is pleurisy. Interstitial lung disease (ILD) is less common in SLE and is seen in patients who have anti–U1-RNP antibodies. Imaging findings are nonspecific; however, ground-glass opacities or consolidations may be present. PNLH has not been described in association to or as a manifestation of SLE in medical literature. There is paucity of data for correlation and larger studies are required to study this potential association. CONCLUSIONS: Pulmonary nodular lymphoid hyperplasia is a rare benign lymphoproliferative disorder. After malignancy and infectious etiology is ruled out autoimmune disease should be considered in patients with PNLH. Further work is warranted to establish this relation. Reference #1: Abbondanzo SL, Rush W, Bijwaard KE, Koss MN. Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases. Am J Surg Pathol. 2000;24(4):587–597. Reference #2: Song MK, Seol YM, Park YE, et al. Pulmonary nodular lymphoid hyperplasia associated with Sjögren's syndrome. Korean J Intern Med. 2007;22(3):192–196. doi:10.3904/kjim.2007.22.3.192. Reference #3: Quadrelli SA, Alvarez C, Arce SC, et al: Pulmonary involvement of systemic lupus erythematosus: analysis of 90 necropsies. Lupus 2009; 18: pp. 1053-1060 DISCLOSURES: No relevant relationships by William Han, source=Web Response No relevant relationships by Immad Munawar, source=Web Response No relevant relationships by Theresa Nicol, source=Web Response

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.

GLILD Revisited: Pulmonary Pathology of Common Variable and Selective IgA Immunodeficiency.

Common variable immunodeficiency (CVID) and selective immunoglobulin A deficiency (IgAD) often cause chronic lung disease, but the pulmonary pathologic features of these systemic diseases are poorly recognized by pathologists. It has been claimed that CVID cases show a characteristic combination of noncaseating granulomas-lymphoid proliferations termed granulomatous-lymphocytic interstitial lung disease (GLILD). We present 34 surgical lung biopsy cases of CVID and 4 of IgAD. Noncaseating granulomas were seen in 23/34 (68%) CVID and 2/4 (50%) IgAD cases. A statistically identical pattern of benign lymphoid proliferation was found in CVID and IgAD whether or not granulomas were present. Organizing pneumonia, sometimes considered a part of GLILD, was seen in 25/34 (74%) CVID and 2/4 (50%) IgAD cases and did not correlate with the presence of granulomas. On follow-up, 3 CVID patients died (only 1 of pulmonary disease), while 21 others are alive at 1 to 300 months with no difference by presence or absence of granulomas. Three IgAD patients with follow-up are alive. We conclude that CVID and IgAD are indistinguishable in surgical lung biopsies and a subset of both show patterns that would qualify as GLILD, while other cases lack granulomas but have identical patterns of lymphoid infiltration and organizing pneumonia. We suggest that GLILD is neither a specific nor a useful entity, and biopsies from CVID and IgAD patients should be diagnosed simply by microscopic pattern(s) observed. The prognosis of CVID with lymphoid infiltrates with or without granulomas in this series was good, contrary to claims in the literature about GLILD.

Methotrexate-associated lymphoproliferative disorder in the stomach and duodenum: a case report

BackgroundMethotrexate-associated lymphoproliferative disorder (MTX-LPD) can present as a benign lymphoid proliferation or a malignant lymphoma in patients taking MTX. Almost 50% of MTX-LPD cases show spontaneous remission after withdrawal of MTX treatment. Studies have suggested that the hyper-immune state of rheumatoid arthritis, the immunosuppressive state associated with MTX, and the carcinogenicity of the Epstein-Barr virus might contribute to MTX-LPD development. Although most cases of MTX-LPD occur at extranodal sites, few cases of MTX-LPD affecting the stomach and duodenum have been reported. To our knowledge, no other study has reported on the endoscopic observations of dramatic withdrawal and appearance of multiple digestive tract lesions in a short period of time. Herein, we report the clinical course and imaging findings of our case, which may be useful for understanding the pathological condition of MTX-LPD.Case presentationWe describe the case of a 70-year-old woman with MTX-LPD of the stomach and duodenum. Disease regression was temporarily achieved after cessation of MTX treatment; however, it subsequently recurred, and complete response was only achieved after six cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (R-CHOP) chemotherapy.ConclusionsThe first-choice therapy for patients taking MTX who develop suspected MTX-LPD should be the withdrawal of MTX treatment. Even after remission is achieved, patients should be kept under careful observation, and if the disease recurs, chemotherapy should be commenced promptly.

Impact on clinical follow‐up of the Milan System for salivary gland cytology: A comparison with a traditional diagnostic classification

No universally accepted classification exists for salivary gland FNA. The proposed Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) offers a uniform classification with management recommendations. We compared FNA diagnoses from a prior study with specific diagnoses with corresponding MSRSGC diagnoses. One-hundred and sixty-four cases from a prior cytological study with histological follow-up were re-reviewed by one of the authors and assigned to one of the MSRSGC categories. The original and MSRSCG diagnoses were compared, as were follow-up recommendations. The MSRSGC system classified 29 specimens as non-diagnostic (seven histologically shown to be benign salivary gland, two non-mucinous cysts, 14 sialadenitis, one pleomorphic adenoma, one haemangioma, one lymphoma, one adenoid cystic carcinoma, one squamous carcinoma and one benign lymphoid proliferation). The original study diagnosed these lesions as: seven benign cysts, 15 benign salivary gland tissue, one benign neoplasm and two insufficient for diagnosis. In seven cases, MSRSGC disagreed with original diagnoses and surgical resection showed lesions where optimal follow-up was more consistent with original cytological diagnosis. In 10 cases with disagreement, the MSRSGC was associated with a more appropriate follow-up based on the surgical diagnosis. Malignancy risks for the Milan categories were: non-diagnostic (12%), non-neoplastic (5%), atypia of undetermined significance (19%), neoplasm, benign (5%), neoplasm (40%), suspicious for malignancy (60%) and malignant (93%). MSRSGC was comparable with the original reported diagnoses in the majority of cases. Both systems had high accuracy for distinguishing benign from malignant lesions and both were associated with appropriate follow-up in most cases.

Cutaneous pseudolymphoma: An enigma

Cutaneous pseudolymphoma, also called lymphoid infiltrates of the skin mimicking lymphomas, is defined as reactive polyclonal benign lymphoproliferative process predominantly composed of either B-cells or T-cells, localized or disseminated. A 62-year-old male presented with multiple asymptomatic swellings over the posterior aspect of the left ear of 1-year duration. On examination, multiple nodules were present over the left retroauricular area, 2 of which were skin colored, firm, and nontender. Histopathology revealed pseudolymphoma with the features of a dense diffuse and nodular infiltrate of small and large lymphocytes and histiocytoid cells involving the whole of reticular dermis and extending to subcutis. A patch test was done using Indian standard battery series showed positive reaction - 2+ for paraphenylenediamine. A diagnosis of cutaneous pseudolymphoma was made. The lesions were treated with intralesional Triamcinolone acetonide injection 10 mg/ml for 2 sittings, 3 weeks apart following which there was remission of the nodules. Pseudolymphomas are benign but persistent lymphoid proliferations in the dermis, which may be difficult to distinguish from a low-grade malignant lymphoma. Pseudolymphomas are classified according to the histological components into B-cell and T-cell variants. So far no case of cutaneous pseudolymphoma suggestive of insect bite with coincidental paraphenylenediamine allergy has been reported. Hence, this case is reported as its histopathology was suggestive of pseudolymphoma secondary to insect bite reaction.

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.

Angiolymphoide Hyperplasie mit Eosinophilie und Morbus Kimura – ein klinischer und histopathologischer Vergleich

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular neoplasm mainly affecting middle-aged women. Lesions typically affect the head and neck region. ALHE is considered a distinct disease entity different from Kimura's disease, a benign reactive lymphoid proliferation that is predominantly seen in young Asian men although it can affect all ethnic groups. In contrast to ALHE, Kimura's disease is typically associated with peripheral blood eosinophilia, increased serum IgE and lymphadenopathy. Several case reports suggest an overlap between ALHE and Kimura's disease. We review the current literature and discuss whether AHLE and Kimura's disease might represent two extreme variants of the same disease entity.

The evolution of clonality testing in the diagnosis and monitoring of hematological malignancies

Currently, distinguishing between benign and malignant lymphoid proliferations is based on a combination of clinical characteristics, cyto/histomorphology, immunophenotype and the identification of well-defined chromosomal aberrations. However, such diagnoses remain challenging in 10-15% of cases of lymphoproliferative disorders, and clonality assessments are often required to confirm diagnostic suspicions. In recent years, the development of new techniques for clonality detection has allowed researchers to better characterize, classify and monitor hematological neoplasms. In the past, clonality was primarily studied by performing Southern blotting analyses to characterize rearrangements in segments of the IG and TCR genes. Currently, the most commonly used method in the clinical molecular diagnostic laboratory is polymerase chain reaction (PCR), which is an extremely sensitive technique for detecting nucleic acids. This technique is rapid, accurate, specific, and sensitive, and it can be used to analyze small biopsies as well as formalin-fixed paraffin-embedded samples. These advantages make PCR-based approaches the current gold standard for IG/TCR clonality testing. Since the completion of the first human genome sequence, there has been a rapid development of technologies to facilitate high-throughput sequencing of DNA. These techniques have been applied to the deep characterization and classification of various diseases, patient stratification, and the monitoring of minimal residual disease. Furthermore, these novel approaches have the potential to significantly improve the sensitivity and cost of clonality assays and post-treatment monitoring of B- and T-cell malignancies. However, more studies will be required to demonstrate the utility, sensitivity, and benefits of these methods in order to warrant their adoption into clinical practice. In this review, recent developments in clonality testing are examined with an emphasis on highly sensitive systems for improving diagnostic workups and minimal residual disease assessments.

Atypical lymphoid proliferations: the pathologist’s viewpoint

Lymphoid proliferations are traditionally thought to be either benign conditions (reactive hyperplasia and lymphadenitis) or malignant lymphomas. However, not all lymphoid lesions at present can be precisely placed into one of these categories. Therefore, in addition to these two extremes, there also exist a third group of lymphoid proliferations – the atypical lymphoid proliferations (AtLP). AtLP is a descriptive term used when it is not possible for the pathologist to differentiate between the benign and the malignant nature of a given lymphoid infiltrate. AtLP represent biologically indeterminate lesions that have some worrisome clinicopathologic features but cannot be interpreted as malignant lymphomas using all criteria currently available. They have some likelihood for subsequent transformation into lymphomas, and therefore AtLP occupy a middle ground between benign and malignant lymphoid proliferations. Nevertheless, sometimes AtLP are not necessarily premalignant and may very well represent a fully benign situation mimicking malignancy. In the author’s opinion, when confronted with a challenging lymphoproliferative lesion, the pathologist should marshall all resources available to interpret it as precisely as possible and therefore place it into one of the two categories: unequivocally benign condition or malignant lymphomas. The resources should include immunohistochemical and molecular studies, obtaining expert opinion and rebiopsy. However, if clinical, morphologic and molecular findings are not sufficient for diagnosis of a benign condition versus lymphoma, the descriptive term AtLP can be used. In the author’s opinion, the use of this descriptive term AtLP may obviate the need to force some lymphoid proliferations (equivocal lesions or mimickers of lymphomas) into either the benign or malignant categories.

Lymphoid Proliferations Associated With Human Immunodeficiency Virus Infection

Individuals who are immune deficient are at an increased risk for developing lymphoproliferative lesions and lymphomas. Human immunodeficiency virus (HIV) infection is 1 of 4 clinical settings associated with immunodeficiency recognized by the World Health Organization (WHO) in which there is an increased incidence of lymphoma and other lymphoproliferative disorders. To describe the major categories of benign lymphoid proliferations, including progressive HIV-related lymphadenopathy, benign lymphoepithelial cystic lesions, and multicentric Castleman disease, as well as the different types of HIV-related lymphomas as defined by the WHO. The characteristic morphologic, immunophenotypic, and genetic features of the different entities will be discussed in addition to some of the pathogenetic mechanisms. The WHO classification of tumors of hematopoietic and lymphoid tissues (2001 and 2008), published literature from PubMed (National Library of Medicine), published textbooks, and primary material from the authors' current and previous institutions. HIV infection represents one of the clinical settings recognized by the WHO in which immunodeficiency-related lymphoproliferative disorders may arise. Although most lymphomas that arise in patients with HIV infection are diffuse, aggressive B-cell lesions, other lesions, which are "benign" lymphoid proliferations, may also be associated with significant clinical consequences. These lymphoproliferations, like many other immunodeficiency-associated lymphoproliferative disorders, are often difficult to classify. Studies of HIV-associated lymphoid proliferations will continue to increase our understanding of both the immune system and lymphomagenesis.

Mantle Cell Lymphoma and Involvement of the Orbit and Ocular Adnexa

Orbital and ocular adnexal lymphomas are rare and represent around 1-2% of lymphomas and about 8% of the extranodal lymphomas. However, these entities represent the majority of orbital malignancies. Lymphomas of the ocular adnexal region are primary or secondary lymphomas, and the majority of them are composed of small, mature lymphocytes, which provide a large differential diagnosis. Thus, these entities are not easily distinguished from indolent lymphoid processes such as reactive lymphoid hyperplasia. Extranodal marginal zone lymphoma is the most common lymphoma in the ocular adnexal region. However, this entity cannot be distinguished from benign lymphoid proliferations or other lymphomas composed of small, mature lymphocytes by routine histopathology. We describe a 78-year-old man who presents with bilateral upper eyelid masses, which had been present and grew in size over the past twelve months prior to his presentation. A biopsy of the mass shows a monotonous population of small, mature lymphocytes. The immunohistochemical studies performed on the eyelid mass confirmed a monoclonal proliferation of B cells expressing cyclin-D1; therefore, a final diagnosis of mantle cell lymphoma was rendered. A literature review of mantle cell lymphoma with orbital and ocular adnexal involvement and the diagnostic pitfalls in this area of hematopathology are discussed.

Selected Topics on Lymphoid Lesions in the Head and Neck Regions

Lymphoid tissue located in the head and neck region include multiple regional lymph node chains as well as mucosa associated lymphoid tissue of the conjunctiva, buccal and nasopharyngeal cavities (Waldeyer's ring), and thyroid and salivary glands. This region is a rich source of antigenic stimuli including infectious agents coming from the outside environment. Many reactive conditions that affect lymphoid tissue in this region may mimic neoplasia. In fact, distinguishing between benign and malignant lymphoid proliferations in the head and neck region is a relatively frequent diagnostic challenge and in many instances, this distinction is not straightforward. It therefore behooves the practicing pathologist to be able to recognize the benign lymphoproliferative disorders that affect this region so as to effectively guide the appropriate clinical management of such patients. Kimura disease, Epstein Barr lymphadenitis, HIV associated salivary gland disease and chronic sialadenitis are benign conditions that not infrequently affect lymphoid tissue in the head and neck region and that share certain overlapping features with malignant lymphoma. In this brief review, we discuss these conditions and highlight clinicopathological features that may help distinguish them from neoplastic lymphoproliferations that may share similar features.

Lymphoproliferative disorders in the immunosuppressed

Lymphoproliferative disorders occur at a higher frequency in immunosuppressed patients than in the general population and these are a group of diseases that range from benign lymphoid proliferations to full-blown lymphomas. These proliferations develop as a consequence of immunosuppression. Their histological appearances and immunophenotypic features are varied. While some resemble lymphoid lesions seen in immune competent patients, others have unique characteristics, with some posing diagnostic problems. Furthermore, within some clinical contexts like the post-transplant setting, the distinction between benign and malignant proliferations is blurred. Identification of specific entities requires a clear understanding of clinical context and morphology, together with a wide immunohistochemical panel, investigations for viral association and clonality studies. Precise identification of the disease entity has an impact on patient management and follow-up.