Reactive Follicular Hyperplasia Research Articles

Advanced Pediatric-Type Follicular Lymphoma, Consequences of a Late Presentation in a Resource-Poor Setting: Case Report and Literature Review

AbstractPediatric-type follicular lymphoma (PFL) is a rare, nonaggressive, slow-growing (indolent), non-Hodgkin lymphoma that is typically seen in males as a localized disease with excellent outcomes. It is largely different from follicular lymphoma (FL). Few published studies on PFL are case series in developed nations. We report on a patient with advanced PFL, a 14-year-old female with 5-year history of neck swellings, abdominal distension for a month, and pericardial effusion, among others. The swellings waxed and waned; and involved all the peripheral lymph nodes. Tuberculosis (TB) GeneXpert and human immunodeficiency virus (HIV) screening were negative. She received anti-TB drugs prior to presentation in our hospital where nodal histopathology showed effaced architecture with diffuse follicles and abundant blastoid cells as well as negative CD5 and BCL2, and positive CD10 and CD20. Diagnosis of PFL (stage 3) was made. She completed six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone and is well 9 months after therapy. The PFL usually presents with stage 1 or 2 disease unlike in the index female case that was also complicated by effusion and ascites due to late presentation. It responded to chemotherapy and has not reoccurred; in contrast to classic FL and reactive follicular hyperplasia (RFH) which should be differentiated from PFL. Although RFH can be caused by TB or HIV, they are not causes of malignant lymphadenopathy. Physicians should be aware of PFL which may present in high clinical stages, but still retain its good prognosis, for the purposes of counseling.

Mechanisms of impaired expression of p53-responsive microRNA genes in diffuse B-large cell lymphoma

Introduction. A more in-depth description of molecular events that disrupt the functioning of the p53 signaling pathway is important for understanding the mechanisms of formation and progression of diffuse B-large cell lymphoma (DCCL), as well as its sensitivity to treatment. The p53 protein exhibits its oncosuppressive function and mediates the antitumor effects of drugs by regulating transcription and/or maturation of a wide range of target genes, including MIR-34A, MIR34B/C, MIR-129-2 and MIR-203. In the tumor tissue of lymphomas, in comparison with normal lymphoid tissue, a decrease in the level of microRNAs encoded by these genes is shown.Aim. The aim of this study was to conduct a comprehensive analysis of the methylation of the genes of the p53-responsive microRNAs MIR-34A, MIR-34B/C, MIR-203 and MIR-129-2, as well as mutations in the DNA-binding domain and destruction of the polyadenylation signal of the TP53 gene in DLBCL.Materials and methods. 136 DNA samples isolated from tumor tissue of patients with DLBCL and 11 DNA samples obtained from lymph nodes with reactive B-cell follicular hyperplasia were analyzed. The methylation status of MIR-203 and MIR-129-2 genes was determined by the method of methyl-specific polymerase chain reaction, MIR-34A and MIR-34B/C genes by the method of methyl-sensitive analysis of high-resolution melting curves. In tumor samples, rs78378222 genotyping was performed by polymerase chain reaction with restriction fragment length polymorphism, resulting in the destruction of the polyadenylation signal, and the nucleotide sequence of the region of the TP53 gene encoding the DNA-binding domain was determined by capillary direct sequencing by Sanger.Results. The methylation detected in lymphoma tissue was tumor-specific. The frequency of analyzed aberrations in the TP53 gene and methylation of MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 was 21, 23, 55, 65 and 66 %, respectively. At the same time, methylation of the analyzed genes of p53-responsive microRNAs and aberrations in the TP53 gene in the tumor tissue of patients with DLBCL were independent events with a tendency to mutual exclusion. At the same time, it was shown that in the vast majority of lymphoma samples, the methylation of the MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes was combined.Conclusion. Along with aberrations in TP53, methylation of MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes may be an important cause of decreased expression of miR-34a, miR-34b, miR-34c, miR-129 and miR-203 in DLBCL. The combined methylation of the MIR-203, MIR-129-2 and MIR-34B/C genes, as well as the MIR-34B/C and MIR-34A pairs, potentially has a more pronounced pro-tumor effect due to the presence of common targets in the microRNAs encoded by them.

Syphilis in Hematopathology Practice: A Diagnostic Challenge.

Syphilis, a reemerging disease caused by spirochete Treponema pallidum, is becoming more frequent in surgical pathology and hematopathology practices. Hematopathologists typically receive lymph node biopsies from patients with syphilis who have localized or diffuse lymphadenopathy. Occasionally, syphilis infection in the aerodigestive tract can show a prominent lymphoplasmacytic infiltrate and mimic lymphoma. Besides the varying and occasional atypical morphology, the fact that clinical suspicion tends to be low or absent when histologic evaluation is requested adds to the importance of making this diagnosis. To summarize histologic features of syphilitic lymphadenitis and syphilis lesions in the aerodigestive tract, and to review differential diagnosis and potential diagnostic pitfalls. Literature review via PubMed search. Characteristic histologic findings in syphilitic lymphadenitis include thickened capsule with plasma cell-rich inflammatory infiltrate, reactive follicular and paracortical hyperplasia with prominent lymphoplasmacytic infiltrate, and vasculitis. Lymph nodes, however, can show a number of other nonspecific histologic features, which frequently makes the diagnosis quite challenging. In the aerodigestive tract, syphilis is characterized by plasma cell-rich infiltrates. Immunohistochemistry for T pallidum is the preferred method for detecting spirochetes; however, this immunohistochemical stain shows cross-reactivity with other treponemal and commensal spirochetes. Differential diagnosis of syphilis in lymph nodes and the aerodigestive tract is broad and includes reactive, infectious, and neoplastic entities. Pathologists should be aware of the histologic features of syphilis and keep this challenging entity in the differential diagnosis.

DP22 Cutaneous lymphoid hyperplasia: clinicopathological correlation and a therapeutic option

Abstract Cutaneous reactive lymphoid hyperplasia, also known as cutaneous pseudolymphoma, is an uncommon entity in which there are skin lesions that histologically, and sometimes clinically, mimic cutaneous lymphoma but are not, both morphologically and immunohistochemically. Correlating clinical, pathological, immunohistochemical and, occasionally, molecular findings is essential for the diagnosis (Romero-Perez D, Blanes Martinez M, Encabo-Duran B. Pseudolinfomas cutaneous. Actas Dermosifiliogr 2016; 107:640–51). Although the majority of cases can be regarded as idiopathic, certain infections and inflammatory conditions can precipitate cutaneous reactive lymphoid hyperplasia, examples of which include Borrelia infection, insect bite reactions and folliculitis (Mitteldorf, C, Kempf, W. Cutaneous pseudolymphoma – a review on the spectrum and a proposal for a new classification. J Cutan Pathol 2020; 47:76–97). The first case was an 18-year-old woman who presented with deep dermal and subcutaneous nodules for the last 5 years that started on her limbs and were slightly itchy. The nodules were firm and deep, with minimal surface changes (hyperpigmentation and adherent scale) but did not ulcerate. She also had nodules involving her buccal mucosa, inner lips and soft tissue in the nasal bridge and a couple of deep nodules on the cheeks. Pathological examination showed a dense lymphocytic infiltrate with plasma cells admixed with other inflammatory cells involving the deep dermis with an extension to the dermal/subcutaneous junction. The pathological picture was in the spectrum of deep tumid lupus/lupus panniculitis overlap and cutaneous lymphoid hyperplasia. Immunohistochemical stains showed a mixture of inflammatory cells with CD3+ and CD20+ cells. Lip mucosal biopsy showed florid reactive lymphoid follicular hyperplasia. Her condition was resistant to multiple systemic treatments. Eventually, she underwent treatment with rituximab and had satisfactory results. The second patient is an elderly female who had multiple erythematous papules, plaques and nodules on her face. Pathological examination showed a dense dermal lymphocytic infiltrate with periadnexal predilection and reactive follicles that also were highlighted by CD20, with Bcl2 and CD3+ cells around germinal centres. She was diagnosed as having cutaneous reactive lymphoid hyperplasia. Topical calcineurin inhibitors were initiated, with a good response. In conclusion, this paper highlights the term cutaneous pseudolymphoma/cutaneous reactive lymphoid hyperplasia, presenting a few cases with clinicopathological correlation and exploring some uncommon treatment options.

Antibody response and abomasal histopathology of lambs with haemonchosis during supplementation with medicinal plants and organic selenium

We evaluated the effects of dietary supplementation with medicinal plants (Herbmix) or organic selenium (Selplex) on the immune responses and histopathology of lambs infected with Haemonchus contortus. Twenty-seven lambs were infected and reinfected with approximately 11,000 third-stage larvae of H. contortus during the experiment (on days 0, 49 and 77). Lambs were divided into two supplemented experimental groups (Herbmix and Selplex) and unsupplemented group (Control). The abomasal worm counts at necropsy on day 119 were lower for Herbmix (4230) and Selplex group (3220) than to the Control (6613) which resulted in 51.3% and 36.0% of reduction, respectively. The mean length of adult female worms was in the order Control > Herbmix > Selplex (2.1, 2.08, and 2.01 cm, respectively). The specific IgG response against adults was significantly affected by time (P < 0.001). Serum-specific and total mucus levels of IgA in the Herbmix group were highest on day 15. Mean levels of serum IgM against adults were influenced by treatment (P = 0.048) and time (P < 0.001). The Herbmix group had strong local inflammation in the abomasal tissue, with the formation of lymphoid aggregates and the infiltration of immune cells, but the tissues of the Selplex group had higher numbers of eosinophils, globule leukocytes, and plasma cells. The lymph nodes of each animal had reactive follicular hyperplasia due to the infection. Dietary nutritional supplementation with a mixture of medicinal plants or organic selenium could improve local immune responses and thus enhance the resistance of animals to this parasitic infection.

Kimura's disease

The analysis of published clinical observations on the diagnosis and treatment of patients with Kimura's disease, which is a rather rare chronic inflammatory disease of human soft tissues of unknown etiology, is presented. The onset of Kimura's illness is hardly noticeable. The disease proceeds sluggishly, with a varied clinical picture, most often with the formation of single or multiple subcutaneous nodules or tubercles and swelling in the head and neck on one or both sides. Other localizations of lesions are also described: limbs, orbit, eyelids, palate, pharynx, armpit, chest, inguinal region. The affected areas gradually increase in size over many months or years. Other clinical manifestations of Kimura's disease are presented in the form of edema of the extraocular muscle, juvenile temporal arteritis, sleep apnea in cases of damage to the larynx, and life-threatening coronary artery spasm in children. There are reports of other rare systemic clinical signs of Kimura's disease in the form of pruritus, eczema and rash. The disease is often associated with regional lymphadenopathy and/or salivary gland involvement, eosinophilia, and an increase in serum immunoglobulin E from 800 to 35,000 IU/mL. The disease may be accompanied by kidney damage in the form of glomerulonephritis and nephrotic syndrome. Most reported cases of Kimura's disease occur in young Asian men in their 20s and 30s, sporadically the disease is diagnosed in Europeans, North Americans, Caucasians, and Africans. Diagnosis of Kimura's disease is often clinically difficult. It is primarily based on excisional biopsy of the lesion or regional lymph nodes, and the histopathological findings are consistent regardless of the location of the lesion. Morphologically, Kimura's disease is characterized by the presence in biopsy specimens of such histological features as reactive follicular hyperplasia with prominent follicles surrounded by fibrous tissue. Interfollicular infiltrates are rich in plasma cells and eosinophils, which form diffuse eosinophilic microabscesses associated with granulomatous inflammation. The vessels are numerous, with an increase in postcapillary venules. At the same time, the blood vessels remain thin-walled, with cuboidal endothelial cells. Treatment issues are highlighted, and differences between Kimura's disease and angiolymphoid hyperplasia with eosinophilia are presented.

Transcriptome analysis of tissue microbiota diversity in tumor and non-tumor lymph nodes

Metagenomic studies in recent years have demonstrated that all tissues of the human body studied by genomic and transcriptomic sequencing methods, both in pathological processes and in normality, contain fragments of DNA and RNA from a variety of microorganisms. The composition of tissue microbiota and its relationship with development of pathological changes are still poorly understood, despite increasing number of studies in this area every year. In this study, gene expression of the lymph node microbiome in reactive follicular hyperplasia and follicular lymphoma was investigated. To study expression of lymph node microbiome genes in reactive follicular hyperplasia and follicular lymphoma. The work included 38 biopsy samples of lymph nodes with follicular lymphoma of different cytological subtypes and 10 biopsy samples of lymph nodes with reactive follicular hyperplasia. Verification of diagnosis was carried out using standard histological, histochemical and immunohistochemical methods. Using sequencing method, the transcriptome was examined. Statistical analysis and data visualization were performed using the R programming language (version 4.2.1). Tumor lymph nodes are characterized by large Simpson and Shannon alpha diversity values (p-value = 0.026465 and p-value = 0.007122, respectively). Two clusters were discovered, characterized by different levels of relative abundance of microorganisms. It has been proven that diversity of microorganisms present in tumor tissue and their number are statistically significantly higher than corresponding indicators in the lymph nodes with follicular hyperplasia.

Оценка метилирования генов MIR-143 и MIR-145 в лимфоузлах больных диффузной В-крупноклеточной лимфомой

Introduction. The expression of miR-143 and miR-145 oncosuppressive microRNAs is observed in all types of normal tissues studied and, according to numerous studies, it is lost in malignant neoplasms. A decrease in the expression of these microRNAs in diffuse large B-cell lymphoma (DLBCL) is described, the mechanisms of which require additional study. Aim. To evaluate the methylation of MIR-143 and MIR-145 genes in the lymph node tissue of patients with DLBCL and lymph nodes of patients with reactive follicular hyperplasia. Materials and methods. The study included biopsies of 14 formalin-fixed and paraffinized tumor lymph nodes of patients with DLBCL and 11 lymph nodes of patients with reactive lymphadenopathy. The methylation status of the MIR-145 gene in samples was determined by the method of methyl-specific polymerase chain reaction. Direct bisulfite sequencing based on the Sanger method was used to quantify the methylation of the MIR-143 gene. Results. It was found that all the studied samples, both reactive and tumor, had methylation of the MIR-145 gene. A similar level of methylation of CpG dinucleotides of the MIR-143 gene was registered in all samples of reactive lymph node tissue, whereas tumor samples showed greater heterogeneity. In the samples of DLBCL, namely a non-germinal B cell phenotype, the average level of methylation of the studied fragment of the MIR-143 gene sequence was significantly lower, than in the samples of reactive lymph nodes (p = 0.026). Conclusion. The methylation of MIR-143 and MIR-145 genes detected in the lymph nodes of patients with DLBCL is not tumor-specific. The complex cellular composition of the analyzed samples, as well as the different density of microvessels, may explain the differences in the level of MIR-143 methylation in the tissue of reactive and tumor lymph nodes.

The Methylation of the p53 Targets the Genes MIR-203, MIR-129-2, MIR-34A and MIR-34B/C in the Tumor Tissue of Diffuse Large B-Cell Lymphoma.

The regulation of oncogenes by microRNA is a focus of medical research. hsa-miR-203, hsa-mir-129, hsa-miR-34a, hsa-miR-34b and hsa-miR-34c are oncosuppressive microRNAs that mediate the antitumor activity of p53. We seek to evaluate the frequencies, co-occurrence and clinical significance of the methylation of the MIR-203, MIR-129-2, MIR-34A and MIR-34B/C genes in the tumor tissue of diffuse large B-cell lymphoma (DLBCL). The methylation was assessed in 73 samples of DLBCL and in 11 samples of lymph nodes of reactive follicular hyperplasia by Methyl-Specific Polymerase Chain Reaction (MS-PCR) and Methylation-Sensitive High-Resolution-Melting (MS-HRM) methods. All four studied genes were not methylated in the tissue of reactive lymphatic nodes. The methylation frequencies of the MIR-129-2, MIR-203, MIR-34A and MIR-34B/C genes in lymphoma tissue were 67%, 66%, 27% and 62%, respectively. Co-occurrence of MIR-203, MIR-129-2 and MIR-34B/C genes methylation, as well as the methylation of MIR-34B/C and MIR-34A pair genes were detected. The MIR-34A gene methylation was associated with increased International Prognostic Index (IPI) (p = 0.002), whereas the MIR-34B/C (p = 0.026) and MIR-203 (p = 0.011) genes’ methylation was connected with Ki-67 expression level in tumor tissue at more than 45%. We found an increasing frequency of detection of MIR-34A gene methylation in the group of patients with the Germinal-Center B-cell like (GCB-like) subtype of DLBCL (p = 0.046). There was a trend towards a decrease in the remission frequency after the first line of therapy (p = 0.060) and deterioration in overall survival (OS) (p = 0.162) in patients with DLBCL with methylation of the MIR-34A promoter. The methylation of the MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes in DLBCL is tumor-specific and occurs in combination. The methylation of the studied genes may be a potential differential diagnostic biomarker to distinguish between lymphoma and reactive lymph nodes, while its independent predictive value has not been confirmed yet.

Human macrophages and monocyte-derived dendritic cells stimulate the proliferation of endothelial cells through midkine production.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications.

EBV-POSITIVE B-CELL ULCERATIVE PROLIFERATION IN THE ORAL CAVITY

<h3>Objective</h3> Lymphoproliferative disorders (LPDs) are a group of conditions characterized by excessive production of lymphocytes manifested by lymphadenopathy, monoclonal lymphocytosis, and bone marrow infiltration. LPDs are often associated with Epstein-Barr virus (EBV) infection. EBV-associated LPDs most commonly appear in the setting of immunocompromised status such as HIV and in transplantation with the extended use of immunosuppressive medications. Individuals with primary immunodeficiency disorders, such as common variable immunodeficiency disease (CVID) or severe combined immunodeficiency, are also at risk of LPD. <h3>Case Summary</h3> A 67-year-old woman complained of mouth ulcerations for 3 months before presentation that were progressively getting worse. Past medical history included CVID, CD4 lymphopenia, rhinosinusitis, eosinophilic asthma, chronic back pain, anxiety, and depression. Medications included immunoglobulin replacement therapy, mepolizumab, montelukast, albuterol, cetirizine, bupropion, clonazepam, fluoxetine, and gabapentin. The patient was allergic to penicillin and azithromycin. Past surgical history was notable for removal of skin melanoma and total knee replacement. Review of systems included a 3-month, 25-lb weight loss, odynophagia, constipation, weakness, and fatigue. Extraoral examination was unremarkable. Intraoral examination revealed 3 × 2 cm² necrotizing palatal ulcerations bilaterally. Necrotizing ulceration was also noted on multiple areas of the gingiva. Differential diagnosis included acute necrotizing ulcerative periodontitis, deep fungal infection (aspergillosis), and lymphoma/LPD. Complete blood count with differential, EBV polymerase chain reaction (PCR), cytomegalovirus PCR and maxillofacial computed tomography (CT) were ordered. The CT scan was unremarkable and laboratory evaluation was negative except for positive EBV PCR. Oral biopsy demonstrated EBV positive B-cell ulcerative proliferation. Positron emission tomography/CT showed widespread fluorodeoxyglucose (FDG)-avid lymphadenopathy. An axillary lymph node biopsy showed atypical lymphoid proliferation in a background of atypical and reactive follicular hyperplasia most consistent with EBV-negative follicular lymphoma, which appeared histologically distinct from the oral EBV-positive LPD. The patient is currently being treated with single-agent rituximab therapy. <h3>Conclusions</h3> EBV may cause oral diseases including infectious mononucleosis, oral hairy leukoplakia, necrotizing ulcerative mucositis, non-Hodgkin's lymphoma, and EBV-related LPD. Persistent oral lesions in patients with CVID could be related to underlying systemic disease. This case is unique because the patient seemingly had follicular lymphoma unrelated to her EBV-positive LPD oral disease, yet in the setting of severe immunosuppression from CVID.

A Case of Intussusception Due to Reactive Follicular Hyperplasia That Was Difficult to Distinguish from Malignant Lymphoma

A Case of Intussusception Due to Reactive Follicular Hyperplasia That Was Difficult to Distinguish from Malignant Lymphoma

Pulmonary Phaehyphomycosis in Retroviral Disease Patient

Pulmonary phaeohyphomycosis is a rare infection in the lung caused by black fungi containing a cytoplasmic melanin-like pigment. A 42-year-old man with underlying retroviral disease on HAART was investigated for having constitutional symptoms. Despite undetectable viral load and a high CD4 count, he was found to have unexplained significant loss of weight and appetite over a period of 6 months. Clinical examination revealed a cachexic man with multiple inguinal lymphadenopathies. Excisional biopsy of the inguinal lymph node revealed reactive follicular hyperplasia. CT Thorax, Abdomen and Pelvis was arranged to look for occult malignancy or infection and he was found to have multiple non-enhancing subcentimeter lung nodules mainly at the lateral segment of the right middle lobe of his lung. The largest nodule measured about 0.8 x 1.5 x 0.5 (AP x W x CC), with some nodules having an irregular margin with no extension into the adjacent bronchi. Bronchoscopy was done and demonstrated a black patch at the right intermedius, lateral segment of the middle lobe which did not disappear upon bronchial flush or wash. Histopathological examination found focal areas of blackish pigment and the bronchial alveolar lavage sent for fungal culture grew Cladosporium species. The patient was treated with oral Itraconazole with marked clinical improvement. This case highlights an unusual black fungi infection in the lung that stands out not only for its rarity and it's responsiveness to treatment, but also the susceptibility of an RVD positive patient to this infection despite having suppressed viral load and normal CD4 count.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S17

Histopathological Study of Pathological Specimens of Various Organs in a Tertiary Care Hospital in Bangladesh

This retrospective study of histopathological specimens was done at the Department of Pathology of Rajshahi Medical College, Bangladesh, from July 2019 to June 2020, emphasizing challenges and diagnosis outcomes. Data obtained from their case notes included age at admission, the site from where the specimens were collected, and histopathological diagnosis. Out of the 2026 histopathology samples, chronic cervicitis constitutes about 50% of the cases. Serous cystadenoma (about 1/4th cases) was common among ovarian pathology. 54.16% of the breast pathology exhibited Invasive ductal carcinoma. Reactive follicular hyperplasia and lymphoma constitute 49.44% of the lymph node pathology. About 80% of the gall bladder pathology was chronic cholecystitis, and metastatic adenocarcinoma was the commonest pathology involving the liver. Squamous cell carcinoma constitutes about 40% of the skin pathology. Osteosarcoma, osteochondroma, and giant cell tumor were the common pathologies involved in bones. Transitional cell carcinoma constitutes about 45% of urinary bladder pathology, and renal cell carcinomas were the commonest pathology of the kidney. Adenocarcinoma constitutes about 45 % of stomach pathology, 28% of small intestine pathology, and 14% of large intestine pathology. Histopathological specimens at the pathology Rajshahi Medical College department with a wide range of pathologies are a major problem. From this study necessity of screening programs for early cancer detection appeared as a time-demanding issue.&#x0D; TAJ 2021; 34: No-1: 16-25

A young girl with chronic isolated cervical lymphadenopathy found to have lupus lymphadenopathy, progressing to develop lupus nephritis: a case report

BackgroundSystemic lupus erythematosus is a rare autoimmune disorder, with the prevalence in Asia ranging from 30 to 50/100,000. The diagnosis of systemic lupus erythematosus is made according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria, and it does not contain lymphadenopathy as diagnostic criteria. However, lupus lymphadenopathy has an estimated prevalence of 5–7% at the onset of disease, and 12–15% at any stage of the disease.Case presentationA 19-year-old Sinhalese girl had neck nodules since the age of 5 years, which increased in size and became tender since 1 year. She had alopecia and joint stiffness for 6 months. She presented with a 5-day history of worsening joint pain, fever, and painful, enlarging cervical nodules. She had tender cervical lymphadenopathy, and a vasculitic rash on both lower limbs. She had pancytopenia, an erythrocyte sedimentation rate of 92, positive antinuclear antibody titer, and high anti-double-stranded deoxyribonucleic acid (DNA), with low C3 and C4 complements. She had a high reticulocyte count of 5%, with direct and indirect antiglobulin tests being positive, indicating autoimmune hemolytic anemia. Lymph node biopsy showed moderate reactive follicular hyperplasia, with scattered plasma cells and immunoblasts, with varying degree of coagulative necrosis, suggestive of lupus lymphadenopathy. On immunohistochemistry of the lymph node biopsy, Bcl2 was negative, excluding lymphoma. Contrast-enhanced computed tomography of abdomen and chest was normal with no hepatosplenomegaly or lymphadenopathy. Skin biopsy showed leukocytoclastic vasculitis. Later, with development of generalized edema, she was found to have impaired renal function, and renal biopsy showed lupus nephritis. She was started on hydroxychloroquine, prednisolone, and mycophenolate mofetil, and her symptoms improved and lymphadenopathy regressed.ConclusionIn the case of cervical lymphadenopathy in a patient with systemic lupus erythematosus, the possibilities of lupus lymphadenopathy, Kikuchi–Fujimoto disease, and lymphoma should all be considered, after excluding secondary infection due to immunosuppression. Histology confirms the differentiation of these pathologies. It is important to differentiate the cause for lymphadenopathy in systemic lupus erythematosus as the outcome and treatment varies. Lupus lymphadenopathy is usually generalized, but isolated cervical lymphadenopathy could also rarely be the first presentation of systemic lupus erythematosus. Lupus lymphadenopathy can be the only presenting feature, and needs a high index in suspecting systemic lupus erythematosus, though it is not included in the diagnostic criteria.

English

BACKGROUND Lymphadenopathy is a common clinical condition and biopsies are usually undertaken to determine the cause of nodal enlargement, which may be neoplastic or non-neoplastic. The neoplastic disorders are categorized into haematolymphoid malignancies and metastasis, while the causes of non-neoplastic lymphadenopathy are diverse. This study was undertaken to determine the histopathological spectrum in lymph node biopsies. METHODS This was a descriptive study of 357 cases of histologically diagnosed peripheral lymph node biopsies in the Department of Pathology, Govt. Medical College, Thiruvananthapuram, Kerala, S. India conducted from January 2019 to December 2019. Treated cases of malignancies were excluded. RESULTS The non-neoplastic lesions were more common accounting for 67.2 % (240 cases) which included 40.3 % (144 cases) of non-specific reactive lymphoid hyperplasia, 3.9 % (14 cases) of other specific lymphoid hyperplasia, 16.2 % (58 cases) of tuberculous lymphadenitis, 6.7 % (24 cases) of other granulomatous lesions. Neoplastic lesions accounted for 32.8 % (117 cases) and included 16.2 % (58 cases) of non-Hodgkin’s lymphoma, 3.9 % (14 cases) of Hodgkin’s lymphoma and 12.6 % (45 cases) of metastatic lesions. CONCLUSIONS Lymph node biopsy plays an important role in establishing the cause of lymphadenopathy. Among the biopsied nodes, reactive follicular hyperplasia was the most common (40.3 %) followed by Non-Hodgkin’s lymphoma and tuberculous lymphadenitis (16.2 % each) and metastasis (12.6 %). KEYWORDS Lymphadenopathy, Lymph Node, Metastasis, Non-Hodgkin’s Lymphoma, Reactive Lymphoid Hyperplasia, Tuberculosis

Follicular tissue fragments in fine-needle aspiration cytology of lymph nodes: A useful clue in differential diagnosis of follicular lymphoma and reactive follicular hyperplasia.

In Fine-needle aspiration cytology (FNAC) of lymph nodes, tissue fragments derived from follicular structures may be observed in specimens. We defined such tissue fragments as follicular tissue fragments (FTF), and investigated differences in cytological findings for FTFs of each histological type. A total of 41 cases with FNAC of lymph nodes were examined. In these cases, the histopathological diagnoses were reactive lymphoid hyperplasia (RLH) (n=17), follicular lymphoma (FL) (n=13), diffuse large B-cell lymphoma (DLBCL) (n=18), and Burkitt lymphoma (n=1). Specimens were analyzed for the presence of FTFs, and for tingible-body macrophages (TBMs) and monomorphism of lymphocytes in FTFs. FTFs with a maximum diameter of >500 μm were defined as large-FTFs. FTFs were identified in RLH (14/17, 82.4%), FL (13/13, 100%), and DLBCL (3/18, 16.7%). In the RLH subtypes, FTFs were present only in follicular hyperplasia (FH) (14/15, 93.3%) and not in paracortical hyperplasia (0/2). The number of cases with large FTFs among those with FTFs were as follows: RLH (10/14, 71.4%), FL (11/13, 84.6%), and DLBCL (0/3). Similarly, those with TBMs in FTFs were as follows: RLH (13/14, 92.9%), FL (0/13) and DLBCL (2/3, 66.7%). Monomorphism was observed in RLH (1/14, 7.1%) and FL (11/13, 84.6%), but not in DLBCL (0/3). Distinction between FL and FH is possible by identifying large-FTFs. In FL, TBMs are absent in FTFs and lymphocytes often show monomorphism. Therefore, recognizing FTFs and observing details inside the FTFs are useful for identification and differential diagnosis of FL and FH in FNAC of lymph nodes.

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.

Cytokine-related genes play critical roles in extrafollicular growth of follicular lymphoma cells.

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle-related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.

Clinical Significance of Increased FDG Uptake in the Waldeyer Ring and the Nasopharynx Region Identified by PET-CT in Postchemotherapy Follow-up in Patients With Lymphoma: When Should We Perform Biopsy?

PurposeTo identify whether fluorodeoxyglucose (FDG) uptake in the Waldeyer ring (WR)/nasopharyngeal (NP) region by positron emission tomography–computed tomography (PET-CT) was physiologic or pathologic in the follow-up of lymphoma patients receiving postchemotherapy treatment. Patients and MethodsWe retrospectively examined FDG uptake in the WR/NP region in 534 patients with lymphoma as assessed by PET-CT used for both diagnosis and follow-up. ResultsForty-nine patients had FDG uptake in the WR/NP region by PET-CT performed after completion of a chemotherapy regimen. Biopsy was performed for 11 of these patients in whom the uptake was considered to be pathologic, and results indicated the presence of reactive follicular hyperplasia. It was considered to be physiologic in 38 patients. PET-CT was repeated after 1 year, and no significant difference was identified between the standardized maximum uptake values (SUVmax; P = .107). The initial diagnosis of 20 patients was made via biopsy performed in the WR/NP region. The SUVmax for the FDG uptake in these patients, asymmetry, SUVmax of the coexisting lymphadenopathies in the neck, and FDG uptake with a counterpart finding by CT were significantly higher than other groups (P = .047, .001, and .005). ConclusionWhen deciding whether to resample after treatment completion, it should be taken into account that, in addition to the SUVmax of the lesion, asymmetry, and the SUVmax of the coexisting lymphadenopathy in the neck, a crucial criterion is whether the FDG uptake has a counterpart finding by CT.