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Learning Objectives
After completing this course, the reader will be able to:
Determine when lymphadenopathy is of concern and merits biopsy. Identify the benign causes of significant lymphadenopathy. Identify the unusual lymphoproliferative disorders that can cause significant lymphadenopathy.
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The Epstein-Barr virus (EBV) has been shown to be associated with posttransplant lymphoma, Hodgkin's disease, and T-cell lymphoma, in addition to African Burkitt's lymphoma. In a retrospective study of 56 consecutive cases of T-cell lymphoma, EBV DNA was found by Southern blot and in situ DNA hybridization in 10 (20%) of 50 peripheral T-cell lympho...
Nonlymphomatous lymphoid disorders of the lung consist of several entities with varied histology and clinical behavior. On the basis of histologic appearance, six lesions can be identified. They include Castleman's disease, plasma-cell granuloma, pseudolymphoma, lymphocytic interstitial pneumonitis, angioimmunoblastic lymphadenopathy, and lymphomat...
Citations
... TB chiefly affects the pulmonary system besides involving extrapulmonary locations comprising head and neck region, occurring in 0.05-5% of the patients with acquired immunodeficiency syndrome (Brown, & Skarin, 2004). The disease can begin acutely, with fever and severe intoxication, and the inflammatory process can spread from the LN to the subcutaneous tissue and skin. ...
... It is known, that seventy-five percent of all LAPs are localized, with more than 50% being seen in the head and neck area (Brown, & Skarin, 2004 (Freeman, & Matto, 2020). Patient was also concerned about his sore throat persistent for a year. ...
... achieved through biopsy or excisional removal. Tissue diagnosis by fine needle aspiration biopsy or excisional biopsy is the gold standard evaluation (Brown, & Skarin, 2004;Freeman, & Matto, 2020). ...
lymphadenopathy is considered as abnormal finding local or generalized that can be caused by neoplasm or infection, as tuberculosis lymphadenitis. Cervical localization has prevalence in the variety of disorders, can has a similar kind of clinical presentation and to differentiate them becomes extremely difficult. We provided a case report of the new onset of extrapulmonary tuberculosis lymphadenitis in 42-year-old Indian man. The patient complained of multiply enlarged painful lymph nodes on left anterior neck and was also concerned about sore throat persistent for a year. Objective examination and analysis were without evident inflammatory signs. Previous ultrasound, pulmonary and abdominal CT-scan investigations also revealed conglomerate of left mediastinal lymph nodes, moderate splenomegaly. The preliminary diagnosis of lymphoma was excluded due to confirmation of typical tuberculosis lymphadenitis with specific testing and morphological changes of the resected lymphatic node. Sputum microscopy was found to be negative, which meant that the patient was negative for social transmission of tuberculosis. Affected lymph nodes resolved completely after appropriate therapy during one-year treatment. This case report of extrapulmonary tuberculosis highlights the importance of tissue diagnosis in unclear situations. We used clinical protocol for unspecified lymph node enlargement as complete history taking and physical examination that is preliminary for diagnosis, while laboratory tests, imaging diagnostic methods and tissue samplings are gold standard evaluation for definite lymphadenopathy. Tuberculosis lymphadenitis is popularly known as collar stud abscess and is the most common benign cause of cervical lymphadenopathy in endemic areas. This observation determined the details of the immunocompromised state of the patient, conclusion was supported by the evidence of Pseudomonas putida associated pharyngitis. The main differential signs between lymphoma as immunoproliferative disorder and infectious tuberculosis lymphadenitis were provided.
... The death rate of Hodgkin lymphoma and NHL has declined by approximately 4.5% and 2.2% per year, respectively (American Cancer Society 2022). The clinical symptoms of lymphoma are appetite loss, chest pain, and breathing of shortness, abdominal fullness, and swollen lymph nodes at different areas of the body (e.g., neck, underarm, or groin) (Brown and Skarin 2004). There is only one FDA-approved lab companion test for the diagnosis of lymphoma is cobas EZH2 Mutation Test (Table 2). ...
Cancer is a fatal illness that kills millions of people each year. Considering the heterogeneity of the disease, conventional therapies, like radiotherapy and chemotherapy, have limited effectiveness. There can be a variety of genetic factors that contribute to the development of tumors, and certain patients may exhibit different proteins than others. As a result of this inherent variability, cancer is well suited to the ever-expanding practice of personalized and precision medicine. The acquisition of precision medicine data is being conducted in many ways in an effort to better understand cancer molecular differences. Over the past decade, the number of druggable molecular mutations that can be detected in tumors has increased dramatically, providing significant information on tumor diagnosis, prognosis, and survival benefits in several cancer types with biomarker-matching therapies. With the advent of liquid biopsy and the rise of targeted therapies for a variety of tumors, precision oncology is revolutionizing. A summary of precision medicine in cancer treatment and approaches to tailoring individual treatments for different cancer types is presented in this chapter. We describe the clinical applications of liquid biopsy components to assess the blood-based biomarkers that facilitate cancer diagnosis. Additionally, we review various targeted therapies and specific diagnostic tests for different cancers in order to develop personalized medicine, emphasizing the updated information about various tumors to aid the elucidation of results and improve the effectiveness of targeted therapies. Moreover, we elaborate on the experiences gained from basket and umbrella clinical trials for tumor treatment using precision medicine trial designs, suggesting future individualized tumor treatment.KeywordsPrecision medicineLiquid biopsyBiomarkerTargeted therapyBasket trialUmbrella trialOncology
... The death rate of Hodgkin lymphoma and NHL has declined by approximately 4.5% and 2.2% per year, respectively (American Cancer Society 2022). The clinical symptoms of lymphoma are appetite loss, chest pain, and breathing of shortness, abdominal fullness, and swollen lymph nodes at different areas of the body (e.g., neck, underarm, or groin) (Brown and Skarin 2004). There is only one FDA-approved lab companion test for the diagnosis of lymphoma is cobas EZH2 Mutation Test (Table 2). ...
Precision medicine and omics technologies play a critical role in the development and implementation of existing biostatistics and bioinformatics approaches. Investments in the development of data mining algorithms and their application to health data are increasing rapidly. It is possible to reveal the relationships between omic levels in order to evaluate all the omic data obtained in the field of biostatistics and bioinformatics, to determine the biomarkers for the diagnosis and treatment of diseases, to provide detailed disease pathophysiology and personalized treatment options. However, there are many challenges to overcome in identifying relationships in big data, such as high dimensionality, heterogeneity, and highly correlated genomic features. Numerous methods using statistics, machine learning and artificial intelligence tools to address these issues are currently being developed and investigated for omic data analysis.KeywordsBioinformaticsBiomarker discoveryBiostatisticsMachine learningPrecision medicine
... The clinical and radiologic findings of various benign conditions may mimic malignancy, including but not limited to autoimmune diseases, benign lymphoproliferative disorders, infectious diseases and drug hypersensitivity reactions. [3,4] Classic histologic mimics of lymphoma include the polymorphous lymphatic proliferations in the context of acute EBV infection, reactive follicular and interfollicular hyperplasia, the proliferative phase of a Kikuchi histiocytic necrotizing lymphadenitis, IgG4-related lymphadenopathy and the rare autoimmune lymphoproliferative syndrome. These differential diagnoses have been extensively reviewed elsewhere. ...
Rationale:
The diagnosis of lymphoma in routine diagnostics can be challenging due to clinical, morphological and immunphenotypical overlap with unusual reactive processes termed "pseudolymphomas."
Patient concerns:
45-year-old male that underwent surgical debridement for a necrotizing fasciitis of the thigh with concomitant excision of a regional lymph node.
Diagnoses:
The lymph node demonstrated an architecture-effacing activation and proliferation of lymphoblasts and was initially misdiagnosed as an aggressive lymphoma. Only in consideration of the clinical context and with the help of additional immunohistochemical and molecular analyses the final diagnosis of a reactive lymphadenopathy could be made.
Interventions:
No further therapy was required after the final diagnosis of a reactive lymphadenopathy was made.
Outcomes:
The clinical follow-up was unremarkable, with no evidence of residual disease after 6 months.
Lessons:
This case report adds the parafollicular activation and proliferation of blasts and plasmablasts in the drainage area of an active infection to the spectrum of "pseudolymphomas" and reiterizes the importance of placing histopathological findings in the proper context.
... Amyloidosis is characterized by deposition of abnormally folded fibrillar proteins in lymph nodes and organs and may be classified as being primary or secondary. Bilateral mediastinal lymph nodes enlargement, sometimes with calcification, is most typical of the primary form and may resemble sarcoidosis [82]. Many case reports show a role for EBUS-TBNA in diagnosis [83][84][85]. ...
Mediastinal lymphadenopathy is a condition in which one or more mediastinal lymph nodes are enlarged for malignant or benign causes, generally more than 10 mm. For a long time, the only way to approach the mediastinum was surgery, while in last decades endoscopic techniques gained their role in neoplastic diseases. At the present time, EBUS is the technique of choice for studying the mediastinum in the suspicion of cancer, while there are not strong indications in guidelines for the study of benign mediastinal lymphadenopathy. We reviewed the literature, looking for evidence of the role of EBUS in the diagnostics of non-neoplastic mediastinal lymphadenopathy, with special regard for granulomatous disease, both infectious and non infectious. EBUS is a reliable alternative to surgery in non-neoplastic mediastinal lymphadenopathy, even if more evidence is needed for granulomatous diseases other than tuberculosis and sarcoidosis.
... An excision biopsy of the lymph node is the ideal investigation for diagnosis, but it requires local or generalized anesthesia. Fine needle aspiration cytology (FNAC) offers an alternative for diagnosis with little trauma and cost [6]. First FNAC was done in 1904 by two marine officers -Captain E.D.W. Greig and Lieutenant A.C.H. Grey. ...
... It can easily differentiate between malignant and nonmalignant lesions [5]. The diagnostic yield of FNAC can be improved if accompanied by radiological guidance like ultra-sonography and computed tomography scan [6]. ...
Background:
In adults, lymph nodes are not normally palpable. A number of patients with asymptomatic lymphadenopathy never visit physicians for the condition, and thus, this important sign is often missed by the medical practitioner if it is not the presenting complaint. The incidence of lymphadenopathy is suggested to be increasing. While lymphadenopathy is benign and self-limiting in most patients, the underlying disease may range from treatable infectious etiology to malignant neoplasms. In most cases clinical examination and history guide towards the cause of lymphadenopathy. In recent years, fine needle aspiration cytology (FNAC) has become an easy clinical tool (with or without the assistance of CT, MRI, and ultrasound) for the diagnosis of the underlying cause of lymphadenopathy.
Aims and objectives:
To find out the cytomorphological pattern in superficial lymphadenopathy with the help of FNAC.
Materials and methods:
This descriptive cross-sectional study was conducted at HBS General Hospital, Islamabad from January 2017 to June 2019. Patients presenting with superficial lymphadenopathy were included in the study. FNAC was performed by the pathologist, histopathological reports were examined and analyzed using Statistical Package for the Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY). Results: Six hundred and thirty-two patients underwent FNAC. Tuberculous lymphadenitis was the most common diagnosis (56.1%) followed by reactive hyperplasia (28.29%). The sample showed metastatic malignancy 3.36% and lymphoma 2.05%. Cervical lymphadenopathy was the most common site for TB (49.36%). Metastatic cancer observed in cervical lymph nodes was 3.16% and lymphoma was 1.74%.
Conclusion:
FNAC is recognized as a simple and safe diagnostic technique that can diagnose cases of superficial and deep lymphadenopathy easily. The most common cause of superficial lymphadenopathy in our study was tuberculosis with cervical lymph nodes.
... 1,2,6,8,10 Histomorphologically CD is distinct from malignant lymphoma; however, these two lesions can coexist or even, indeed, mimic each other like in this case report. 1,6,[11][12][13][14][15][16][17][18] In such scenarios, immunohistochemical (IHC) evaluation of the lymph node specimen in addition to routine H&E histopathological evaluation becomes the gold standard in arriving at a definitive diagnosis. 1,5,11,[13][14][15]19 This case is reported because of its rarity and thus should be considered in the differential diagnosis of generalized lymphadenopathy, and also to show how important IHC is in resolving diagnostic dilemmas in lymph node pathology. ...
Castleman disease (CD), or angiofollicular hyperplasia, or giant lymph node hyperplasia, is a heterogeneous benign lymphoproliferative disorder of unknown etiology. It has three distinct histologic subtypes (hyaline vascular, plasma cell, and mixed hyaline vascular plasma cell types) as well as unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD) variants. In the unicentric form, the disease is confined to one anatomical lymph node and usually with no systemic symptoms. However, in the multicentric form (further subdivided into idiopathic MCD, human herpes virus-8-associated MCD, and POEMS-associated MCD), lymphadenopathy is more generalized with more aggressive systemic symptoms mimicking a malignant lymphoma. Therefore, this case report aims to underscore the importance of immunohistochemical evaluation as an indispensable ancillary technique to routine histopathological examination of a lymph node biopsy specimen, as a gold standard for definitive diagnosis of proliferative lymph node lesions.
... Here lymph node architecture is preserved in contrast to Hodgkin's disease. [11] The etiology and pathogenesis of PTGC remains unknown. There are various theories to explain its pathogenesis. ...
... [4] According to few studies PTGC is thought to result from antigenic stimulation during immunologic conditions. [5,11] In view of Rosai PTGC is the morphological expression of distinct type of follicular hyperplasia, seen in conjunction with Hodgkin's disease. [7] E X 100, Fig 2B). ...
... [10] In case of PTGC lymph node may remain stable for many years or may transform into Hodgkin's lymphoma (2.5%) or regress spontaneously. [11] In the present case, patient presented with chronic lymphadenopathy for the first time and complete excision was done. Microscopy showed PTGC without any concurrent NLPHL, which was confirmed on IHC and till date there is no evidence of recurrence. ...
Progressive transformation of germinal centers (PTGC) is an uncommon variant of non-specific reactive follicular hyperplasia. PTGC is a clinically asymptomatic condition characterised by persistent lymphadenopathy. PTGC may occur before, concurrently with or after the onset of nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL). It may also be confused for follicular lymphoma and mantle zone lymphoma. We report an interesting case of PTGC in a 23 year female with swelling in the left side of neck of one year duration. Histology revealed PTGC, which was confirmed by immunohistochemistry which showed CD3+, CD20+ in appropriate B and T cell region and negative for CD15, CD30 and bcl-2. As PTGC mimics lymphoma, it should be followed up carefully.
... It is often found incidentally in surgical specimens of lymph nodes, but it can also be present as lymphadenopathy [3]. ...
... Vascular transformation of sinuses (VTS) has variant histological features such as vasodilation with minimal changes and vascular proliferations, which resemble Kaposi's sarcoma [4,5]. These histological features, result of the duration of regional lymphatic and/or venous obstruction [3,5,6]. ...
... Vascular transformation of sinuses (VTS) is a reactive process. The sinuses of lymph node were converted into a complex anastomosing network of vascular channels, which vary from capillaries to cavernous spaces [1,3,[5][6][7]. ...
ABSTRACT
Introduction: Vascular transformation of sinuses (VTS) is a rare reactive process. The lymph node sinuses got converted into a complex anastomosing network of vascular channels.
Case Report: We report a unique case of VTS in a healthy 13-year-old female who complained only of abdominal pain with no other findings. She was misdiagnosed as non-Hodgkin lymphoma by FNA on a retrocaval mass and administered with chemotherapy before performing an excisional biopsy. Her pain recurred after a year; another course of chemotherapy was determined, but the patient and her parents refused it. Another clinician was consulted and he decided to perform an excisional biopsy which revealed VTS with no malignancy.
Conclusion: By reviewing literature, the majority of VTS cases were reported in adults and associated with neoplasia, but the case described here may be the first case to be reported about VTS in a child, who has been healthy to date. We also report this case to emphasize the role of diagnosis before making any therapeutic procedure, in particular chemotherapy
... It was also observed that the dualtargeted bubbles (3.30 ± 6.65 AU) were retained more in benign nodes than control microbubble (0.03 ± 0.24 AU). This could be caused by inflammation in some benign nodes [54,55]. In the future, the dual-targeted bubble retention measure will also be compared to results from immunohistochemical or immunohistofluorescent analyses of angiogenesis. ...
Purpose:
The purpose of this study was to assess the performance of molecular ultrasound with dual-targeted microbubbles to detect metastatic disease in the sentinel lymph nodes (SLNs) in swine model of naturally occurring melanoma. The SLN is the first lymph node in the lymphatic chain draining primary tumor, and early detection of metastatic SLN involvement is critical in the appropriate management of melanoma.
Procedure:
Nine Sinclair swine (weight 3-7 kg; Sinclair BioResources, Columbia, MO, USA) with naturally occurring melanoma were examined. Siemens S3000 scanner with a 9L4 probe was used for imaging (Siemens Healthineers, Mountain View, CA). Dual-targeted contrast agent was created using Targestar SA microbubbles (Targeson, San Diego, CA, USA) labeled with ανβ3-integrin and P-selectin antibodies. Targestar SA microbubbles labeled with IgG-labeled were used as control. First, peritumoral injection of Sonazoid contrast agent (GE Healthcare, Oslo, Norway) was performed to detect SLNs. After that, dual-targeted and IGG control Targestar SA microbubbles were injected intravenously with a 30-min interval between injections. Labeled Targestar SA microbubbles were allowed to circulate for 4 min to enable binding. After that, two sets of image clips were acquired several seconds before and after a high-power destruction sequence. The mean intensity difference pre- to post-bubble destruction within the region of interest placed over SLN was calculated as a relative measure of targeted microbubble contrast agent retention. This process was repeated for non-SLNs as controls. All lymph nodes evaluated on imaging were surgically removed and histologically examined for presence of metastatic involvement.
Results:
A total of 43 lymph nodes (25 SLNs and 18 non-SLNs) were included in the analysis with 18 SLNs demonstrating metastatic involvement greater than 5 % on histology. All non-SLNs were benign. The mean intensity (± SD) of the dual-targeted microbubbles for metastatic SLNs was significantly higher than that of benign LNs (18.05 ± 19.11 vs. 3.30 ± 6.65 AU; p = 0.0008), while IgG-labeled control microbubbles demonstrated no difference in retained contrast intensity between metastatic and benign lymph nodes (0.39 ± 1.14 vs. 0.03 ± 0.24 AU; p = 0.14).
Conclusions:
The results indicate that dual-targeted microbubbles labeled with P-selectin and ανβ3-integrin antibodies may aid in detecting metastatic involvement in SLNs of melanoma.
