Hodgkin Lymphoma Case Study PDF

CBL Pathology A case of lymphadenopathy Hodgkin Lymphoma: A Case Study. Patient Case Overview A 30-year-old male presents with a painless, enlarged lymph node in the right cervical region, persisting for two months. He reports fatigue...

CBL Pathology A case of lymphadenopathy Hodgkin Lymphoma: A Case Study. Patient Case Overview A 30-year-old male presents with a painless, enlarged lymph node in the right cervical region, persisting for two months. He reports fatigue, intermittent fevers, and night sweats. Physical examination reveals firm, non-tender lymphadenopathy. Biopsy confirms Hodgkin lymphoma. Staging workup, including PET-CT, shows involvement limited to the neck and chest. Treatment options, including chemotherapy and radiotherapy, are discussed. Short Essay Questions 1. Discuss the epidemiology and risk factors of Hodgkin lymphoma. 2. Explain the pathophysiology of Hodgkin lymphoma and its implications for treatment. 3. Describe the staging system for Hodgkin lymphoma and its clinical significance. 4. Outline the first-line treatment options for Hodgkin lymphoma. 5. Evaluate the role of follow-up and surveillance in Hodgkin lymphoma management. 1|Page  CBL Pathology Answers 1. Hodgkin lymphoma is more common in young adults, especially males, and may be associated with EBV infection and family history. 2. The pathophysiology involves the transformation of B lymphocytes, leading to the characteristic Reed-Sternberg cells, impacting treatment response. 3. The Ann Arbor staging system ranges from I-IV, affecting treatment decisions and prognosis based on the extent of disease. 4. First-line treatments typically include ABVD chemotherapy and may be supplemented with radiation therapy based on stage. 5. Regular follow-up is essential to monitor for recurrence and manage long-term effects of treatment, including secondary malignancies Multiple Choice Questions  Which of the following is a classic histological finding in Hodgkin lymphoma? a. Reed-Sternberg cells b. Auer rods c. Smudge cells d. Plasma cells  Which Hodgkin lymphoma subtype is most commonly associated with EBV infection? a. Nodular sclerosis b. Mixed cellularity c. Lymphocyte depletion d. Lymphocyte-rich 2|Page  CBL Pathology  What is the most common initial presentation of Hodgkin lymphoma in patients? a. Painless lymphadenopathy b. Jaundice c. Abdominal pain d. Cough  Which stage of Hodgkin lymphoma involves two or more lymph node regions above the diaphragm? a. Stage I b. Stage II c. Stage III d. Stage IV  What is the role of PET-CT in the management of Hodgkin lymphoma?. a. Staging and treatment response evaluation b. Identifying genetic mutations c. Assessing bone marrow involvement d. Measuring lung function  Which chemotherapy regimen is the standard first-line treatment for Hodgkin lymphoma? a. ABVD b. CHOP c. FOLFOX d. ICE  Which symptom is considered a “B symptom” in Hodgkin lymphoma? a. Night sweats b. Itching c. Headache d. Palpitations 3|Page  CBL Pathology  What factor significantly improves prognosis in early-stage Hodgkin lymphoma? a. Absence of B symptoms b. Bone marrow involvement c. Older age d. Bulky disease  Which immune checkpoint inhibitor is used for relapsed Hodgkin lymphoma treatment? a. Pembrolizumab b. Rituximab c. Imatinib d. Bevacizumab  Which subtype of Hodgkin lymphoma has the best overall prognosis? a. Nodular sclerosis b. Mixed cellularity c. Lymphocyte depletion d. Lymphocyte-rich Case scenario A 30-year-old male presents to the clinic with a chief complaint of painless enlarged lymph node in the right cervical region, persisting for two months He also reports experiencing fatigue, intermittent fevers, frequent night sweats and has noticed a 5% unintentional weight loss over the last month. In addition, he mentions occasional episodes of fever. The patient first noted a small, painless swelling in his neck, which has gradually increased in size. He denies any recent infections, exposures, or other symptoms such as itching or cough. He has not taken any medications for these symptoms. Physical examination reveals firm, non-tender lymphadenopathy. 4|Page  CBL Pathology ✓ The patient has no significant past medical or surgical history. ✓ He has no known drug allergies and is on no regular medications. ✓ Clinical Examination: ✓ -Vital Signs: Blood pressure is 120/80 mmHg, heart rate is 80 beats per minute, and temperature is 37.8°C. ✓ -Physical Examination: The examination reveals enlarged, non-tender lymph nodes in the cervical region. ✓ There is no hepatosplenomegaly noted upon abdominal examination. The rest of the physical examination, including respiratory, cardiovascular, and dermatological systems, is unremarkable. ✓ PET-CT, shows involvement limited to the neck and chest. Analysis of the case: ✓ take notes and think about the differential diagnosis ✓ "What are the possible causes of lymphadenopathy in a young adult?“ ✓ What is the importance of a thorough clinical examination in cases where lymphadenopathy is present? ✓ What are the key factors that distinguish Hodgkin lymphoma from other types of lymphoma and non-malignant causes of lymphadenopathy? ✓ what tests they would order to confirm the diagnosis and detect the staging ✓ Discuss with each other. Demographics: A 25-year-old male, software engineer, non-smoker. Chief Complaints: The patient presents with a 2-month history of painless swelling in the neck and recent episodes of night sweats. He also reports significant weight loss (5% of body weight over the last month) and occasional fevers. Clinical Examination Vital Signs: BP 120/80 mmHg, Heart Rate 80 bpm, Temp 37.8°C. Physical Exam: Enlarged, non-tender lymph nodes palpable in the cervical region. No hepatosplenomegaly noted. The rest of the physical examination is unremarkable. 5|Page  CBL Pathology EVALUATION OF LYMPHADENOPATHY Age: *less the 30 years: benign. *older than 50: more malignant. location: examine the drainage areas for infection or malignancy. Generalized lymphadenopathy: almost always indicates a systemic disease is present ,proceed with specific testing as indicated. ASSOCIATED SYMPTOMS. Presence or absence of splenomegaly: with splenomegaly, hematological malignancy is suspected DURATION : also give clue about etiologies and severity. Longer duration of symptoms and lymph nodes enlargement would suggest possible chronic infections like TB or indolent cancers like follicular lymphoma. Malignancy possibilities suggested by symptoms related mechanical compression like dysphagia ,hoarse voice , cough ,haemoptysis and systemic symptoms like weight loss ,anorexia , fatigue PHYSICAL EXAMINATIOn size. pain/tenderness: the presence or absence of tenderness does not reliably differentiate benign from malignant nodes. consistency stony-hard nodes are typically a sign of cancer ,usually metastatic. very firm, rubbery nodes suggest lymphoma. softer nodes are the result of infections or inflammatory conditions suppurate nodes may be fluctuant. 6|Page  CBL Pathology MATTING : can be either: BENIGN (E.G., TUBERCULOSIS, SARCOIDOSIS )OR MALIGNANT (E.G., METASTATIC CARCINOMA OR LYMPHOMA. LOCATION: infectious mononucleosis causes cervical adenopathy and a number of sexually transmitted diseases are associated with inguinal adenopathy Preliminary Assessment The presentation of painless lymphadenopathy along with systemic B symptoms in a young adult raises suspicion for Hodgkin Lymphoma, but other diagnoses such as non-Hodgkin Lymphoma and infectious or inflammatory causes should also be considered. The B symptoms (fever, night sweats, weight loss) B symptoms The term "B symptoms" refers to a set of systemic symptoms that are significant in the diagnosis and staging of Hodgkin lymphoma (HL), as well as in some non-Hodgkin lymphomas (NHL). They are considered important indicators of the severity of the disease and have prognostic value. B symptoms include: Fever: Unexplained fevers with temperatures above 38°C , which may be recurrent and are not attributed to an infection or another cause. Night Sweats: Drenching sweats that require a change of bedclothes, which cannot be attributed to an overheated room or too many bedclothes. Weight Loss: Unintentional weight loss of more than 10% of the body weight over a period of 6 months or less, without trying to lose weight. 7|Page  CBL Pathology Diagnostic Workup: The patient should be advised to undergo further diagnostic tests, including ▪ complete blood count (CBC), ▪ Erythrocyte sedimentation rate (ESR), ▪ lactate dehydrogenase (LDH), and ▪ Imaging studies like chest X-ray and CT scan of the neck and chest to evaluate the extent of lymphadenopathy. An excisional biopsy of the enlarged lymph node is imperative for histopathological diagnosis. Referral: Referral to an oncologist is recommended for management and further workup, including possible bone marrow biopsy and PET scan as part of the staging process. Laboratory Tests CBC: Mild anemia and lymphopenia. ESR: Elevated. Biochemical Tests: Liver and renal function tests within normal limits. Imaging Chest X-ray: Shows no mediastinal lymphadenopathy. CT Neck and Thorax: Reveals enlarged cervical and mediastinal lymph nodes. Biopsy and Pathology An excisional biopsy of a cervical lymph node is performed. Gross Microscopic The largest lymph node was excised Histologically a distinctive neoplastic giant cells called Reed-Sternberg (RS) cells admixed with a variable infiltrate of reactive, nonmalignant inflammatory cells were seen. So the best diagnosis is Hodgkin lymphoma 8|Page  CBL Pathology Diagnosis Multiple enlarged lymph nodes in group of nodes Painful ,large size Rapid onset Increased LDH (tumor marker for lymphoma). Biopsy reveals large atypical lymphoid cells (RS). THUS FROM THE CLINICAL POINT OF VIEW, EXAMINATION , INVESTIGATION AND BIOPSY WE ARE BELIEVING , WE ARE IN FRONT OF CASE OF HD LYMPHOMA. lymphoma. 9|Page  CBL Pathology Hodgkin lymphoma It is a potentially curable lymphoma. It arises almost invariably in a single node or chain of nodes and spreads characteristically to the anatomically contiguous nodes. HL is the most common malignancy of Americans between the ages of 10 and 30 years. Hodgkin lymphoma classification: Classical HL: Nodular sclerosis Mixed cellularity Lymphocyte-rich Lymphocyte depleted Nodular Lymphocyte predominant HL. It is separated from the NHLs for several reasons. 1- it is characterized morphologically by the presence of distinctive neoplastic giant cells called Reed-Sternberg (RS) cells admixed with a variable infiltrate of reactive, nonmalignant inflammatory cells. 2- it is often associated with somewhat distinctive clinical features, including systemic manifestations such as fever. 3- its stereotypic pattern of spread allows it to be treated differently than most other lymphoid neoplasms. The prognosis in HL depends mainly on the patient's age and the anatomic extent of the disease, i.e., the stage. A better prognosis is associated with (1) younger age, (2) lower clinical stage (localized disease), and (3) absence of B signs and symptoms. 10 | P a g e  CBL Pathology Reed-Sternberg (RS) cells Has abundant, usually slightly eosinophilic, cytoplasm. multilobate nucleus or being multinucleate with large, round, prominent nucleoli. Particularly characteristic are two mirror-image nuclei or nuclear lobes, each containing a large (inclusion-like) acidophilic nucleolus surrounded by a distinctive clear zone; together they impart an owl-eyed appearance. The nuclear membrane is distinct. "classic" RS cells are common in the mixed cellularity subtype, uncommon in the nodular sclerosis subtype, and rare in the lymphocyte-predominance subtype; Variants of R.S cells Mononuclear variants : contain a single nucleus with a large inclusion-like nucleolus. Lacunar cells : have more delicate, folded, or multilobate nuclei and abundant pale cytoplasm that is often disrupted during the cutting of sections, leaving the nucleus sitting in an empty hole (a lacuna). Lymphohistocytic variants (L&H cells) Popcorn with polypoid nuclei, inconspicuous nucleoli, and moderately abundant cytoplasm 11 | P a g e  CBL Pathology The prognosis in HL depends mainly on The patient's age and The anatomic extent of the disease, i.e., the stage. A better prognosis is associated with I. Younger age, II. Lower clinical stage (localized disease), and III. Absence of B signs and symptoms. Ann Arbor staging system for lymphoma Stage I - Single lymph node region Stage II - Two or more lymph node regions on same side of the diaphragm Stage III - Involvement of lymph node regions on both sides of the diaphragm Stage IV - Multiple foci of involvement of one or more extralymphatic organs or tissues The presence of B symptoms is associated with a more advanced stage of lymphoma and may affect treatment decisions. In the staging of Hodgkin lymphoma, the presence of B symptoms is denoted with a letter "B" (e.g., Stage IIIB), whereas their absence is denoted with an "A" (e.g., Stage IIIA). Pathogenesis of white cell neoplasms Chromosomal translocations. Inherited genetic factors. Viruses:HTLV-1, HHV-8, EBV. Environmental agents: H pylori, gluten sensitive entropathy. Iatrogenic factors. 12 | P a g e  CBL Pathology Differences between Hodgkin and Non-Hodgkin Lymphomas Hodgkin`s Non-Hodgkin`s Incidence Less common More common Sites Nodal (Single or multiple) Extranodal Nodal (Mostly multiple L.N.s) (less common) extranodal (More common) Destribution More mono-nodal (more in cervical) More Multi-nodal (more than one group) Gross Large - Grayish pink - Firm Large - Pale Grey Soft (Fish flesh) Microscopic -effacement of L.N. architecture effacement of L.N. architecture -Background: mixed inflammatory -Background: malignant cells lymphocytes (B or T) - NO R-S -Malignant Reed-Sternberg (RS) cells cells Immune- RS is positive to CD15, & CD 30 Malignant lymphocytes are staining positive to CD3 (T cells), CD20 (B cells) Clinical Intermittent Fever (Pel-Ebsein fever)- No 2ry B-symptoms Cachexia - Anemia - itching prognosis Better Worse Assessment 1. Which cells are the diagnostic hallmark of Hodgkin lymphoma? A) B lymphocytes B) T lymphocytes C) Hodgkin and Reed-Sternberg cells D) Macrophages 2. What is the characteristic appearance of Reed-Sternberg cells? A) They have small, indistinct nucleoli. B) They contain mirror-image nuclei with large acidophilic nucleoli. C) They have a monolobate nucleus with inconspicuous nucleoli. D) They display a deeply basophilic cytoplasm. 13 | P a g e  CBL Pathology 3. Classic Reed-Sternberg cells are most common in which subtype of Hodgkin lymphoma? A) Nodular sclerosis B) Mixed cellularity C) Lymphocyte-predominance D) Lymphocyte-rich 4. Which subtype of Hodgkin lymphoma is characterized by 'popcorn' or L&H (lymphohistocytic) cells? A) Classical Hodgkin Lymphoma B) Nodular Lymphocyte-Predominant Hodgkin Lymphoma C) Lymphocyte-Depleted Hodgkin Lymphoma D) Mixed-Cellularity Hodgkin Lymphoma 5. What is NOT a feature of Nodular Lymphocyte-Predominant Hodgkin Lymphoma? A) High recurrence rate B) Presence of classic Reed-Sternberg cells C) Lack of eosinophils and plasma cells in the inflammatory background D) Tumor cells negative for EBV 6. Which of the following statements is true regarding Classical Hodgkin Lymphoma? A) It features a clonal proliferation of atypical lymphocytes without Reed-Sternberg cells. B) It is characterized by mononuclear and multinucleated Reed-Sternberg cells with expression of CD30. C) It lacks an inflammatory background. D) It is not divided into different subtypes. 7. Nodular-Sclerosis Hodgkin Lymphoma often presents with: A) Mediastinal involvement and a poor prognosis. B) A mixed inflammatory background without lacunar cells. C) Lacunar cells and fibrosis dividing lymphoid tissue into nodules. D) A high association with EBV in all cases. 14 | P a g e  CBL Pathology 8. Which subtype of Hodgkin lymphoma has the worst prognosis without treatment? A) Nodular sclerosis B) Mixed cellularity C) Lymphocyte-rich D) Lymphocyte-depleted 9. What is the age group most commonly affected by Hodgkin lymphoma? A) 0-10 years B) 10-30 years C) 30-50 years D) Over 50 years 10. Which of the following is NOT a common feature of classic Reed- Sternberg cells? A) Abundant eosinophilic cytoplasm B) Multilobate nucleus or multinucleate C) Small, indistinct nucleoli D) Owl-eyed appearance 11. What unique feature is associated with Reed-Sternberg cells in Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)? A) They express CD15 and CD30 antigens. B) They lack the CD15 and CD30 antigens. C) They are positive for EBV. D) They are typically found in a background of eosinophils and plasma cells. 12. Which subtype of Classical Hodgkin Lymphoma is characterized by lacunar cells? A) Lymphocyte-rich B) Nodular-sclerosis C) Mixed-cellularity D) Lymphocyte-depleted 15 | P a g e  CBL Pathology 13. What is the most common subtype of Hodgkin lymphoma? A) Nodular sclerosis B) Mixed cellularity C) Lymphocyte-rich D) Lymphocyte-depleted 14. Which Hodgkin lymphoma subtype has the highest association with the Epstein-Barr virus (EBV)? A) Nodular sclerosis B) Mixed cellularity C) Lymphocyte-rich D) Lymphocyte-depleted 15. Which subtype of Hodgkin lymphoma is most frequently seen in HIV-1- infected patients? A) Nodular sclerosis B) Mixed cellularity C) Lymphocyte-rich D) Lymphocyte-depleted Answers 1. C) Hodgkin and Reed-Sternberg cells 2. B) They contain mirror-image nuclei with large acidophilic nucleoli. 3. B) Mixed cellularity 4. B) Nodular Lymphocyte-Predominant Hodgkin Lymphoma 5. B) Presence of classic Reed-Sternberg cells 6. B) It is characterized by mononuclear and multinucleated Reed-Sternberg cells with expression of CD30. 7. C) Lacunar cells and fibrosis dividing lymphoid tissue into nodules. 8. D) Lymphocyte-depleted 9. B) 10-30 years 10. C) Small, indistinct nucleoli 11. B) They lack the CD15 and CD30 antigens. 12. B) Nodular-sclerosis 13. A) Nodular sclerosis 14. B) Mixed cellularity 15. B) Mixed cellularity 16 | P a g e