Hodgkin lymphoma Methodic guidelines for the 6th year students Self-training on the practical study icon

Hodgkin lymphoma Methodic guidelines for the 6th year students Self-training on the practical study




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M. Gorky Donetsk National Medical University


Hodgkin lymphoma


Methodic guidelines for the 6th year students

Self-training on the practical study

at the Internal medicine # 1 department


Donetsk – 2010


Authors:

I. A. Petrenko

N. V. Kalinkina, PhD


Reviewers:

T.A. Parkhomenko, MD, PhD, Internal medicine #2 department

R.V. Basiy, MD, PhD, Anatomy department.


I. Introduction:


Hodgkin lymphoma is a cancer of the lymphatic system. It is sometimes called Hodgkin disease.

There are two main types of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Most lymphomas are non-Hodgkin lymphoma and only about 1 in 5 (20%) are Hodgkin lymphoma. Nearly 1500 people are diagnosed with Hodgkin lymphoma in the UK each year.

There is only one way to tell the difference between Hodgkin and non-Hodgkin lymphomas (NHL). The difference can be seen when the cells are looked at under the microscope. Often the cells need to be stained with dyes to show their structures. Usually the cells will also be tested for the presence of particular proteins – this is known as immunohistochemistry.

In most cases of Hodgkin lymphoma (HL), a particular cell known as the Reed-Sternberg cell is found in the tests done to see if you have the disease. This cell is not usually found in other lymphomas, so they are called non-Hodgkin lymphoma. This difference is important, because the treatment for Hodgkin and non-Hodgkin lymphomas can be very different. It is thought that Reed-Sternberg cells are a type of white blood cell – a B-lymphocyte that has become cancerous. B-lymphocytes normally make antibodies to fight infections.


II. Aims of studying the topic

^ Common purpose: you need to know how to differentiate lymphomas, define main strategies of treatment and approach to the patient.

Purposes

Basic skills required:

  1. Define main syndromes of HL in connection with history of disease.




  1. Approach to the patient: complaints, physical examination of the patients. (Propaedeutics and Therapy department)

  1. Compile an individual scheme of diagnostic search. Interpret all necessary data for diagnosing HL. Obtain the stage and histological findings of HL.




  1. To interpret indexes of physical and laboratory examination (complete blood count, biochemical blood examination, ) and instrumental (Sternal puncture, trepanobiopsy, ultrasound of abdomen, lymph node biopsy) examination (Histology, Radiology department)

  1. Making a provisional diagnosis. Differentiate lymphadenopathy according to diagnostic algorithms.




3. To evaluate typical clinical picture of oncological, surgical, infectious diseases with lymphadenopathy (Oncology, Surgery, Infectious Diseases departments). Make up conclusions, formulate a diagnosis due to classifications.

4. Approaches to the treatment of the patients with HL.

4. Use methods of pathogenic and symptomatic therapy in the patients with lymphomas. (Pharmacology department)



Literature for material revise:

1. Bräuninger A, Schmitz R, Bechtel D, Renné C, Hansmann ML, Küppers R (April 2006). "Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma". Int. J. Cancer 118 (8): 1853–61. doi:10.1002/ijc.21716. PMID 16385563.

2. Tzankov A, Bourgau C, Kaiser A, et al. (December 2005). "Rare expression of T-cell markers in classical Hodgkin's lymphoma". Mod. Pathol. 18 (12): 1542–9. doi:10.1038/modpathol.3800473. PMID 16056244.

3. Lamprecht B, Kreher S, Anagnostopoulos, I, Johrens k, Monteleone G, Junt F, Stein H, Janz M, Dorken B, Mathas S (2008). "Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3a". Blood 112 (Oct 2008): 3339–3347. doi:10.1182/blood-2008-01-134783. PMID 18684866.

4. Bobrove AM (June 1983). "Alcohol-related pain and Hodgkin's disease". The Western Journal of Medicine 138 (6): 874–5. PMID 6613116.

5. Portlock CS (July 2008). "Hodgkin Lymphoma". Merck Manual Professional. Retrieved 2009-06-18.

Tests of initial level

1. In CBC leukocyte formula of patient A. is on 68% consisted of small mononuclear cells with a large round dark nucleus and a narrow rim of basophilic cytoplasm.

What are the predominant leukocytes in this patient?

A. bands;

B. neutrophils;

C. eosinophils;

D. monocytes;

E. lymphocytes.


2. B. The patient, 56 years old, complained on peripheral lymphatic nodes enlargement and discomfort in left sumcostal area. Bone marrow cytological study was recommended.

Which bone the bone marrow aspiration should be performed on?

A. humerus;

B. radial;

C. femoral;

D. elbow;

E. sternum.


3. In the CBC of patient V a considerable decrease in the B-lymphocyte level was found. Which immunity immunity type would suffer mostly?

A. anti-tumor immunity;

B. hypersensitivity;

C. immunity against intracellular parasites;

D. antibody formation;

E. transplant rejection.


4. On physical examination of the patient's G blood the doctor found predominance of the dominance of large cells with cytoplasm and basophilic kidney-like nucleus in the leukocyte formula.

How to interprete the data?

A. neutrophilia;

B. eosinophilia;

C. eozinophil-basophilic association;

D. lymphocytosis;

E. monocytosis.


5. The patient D. complained on submandibular left side lymphatic nodes enlargement, splenomegaly, fever, general weakness. In order to clarify the diagnosis bone marrow biopsy was performed. Result: normal.

What was the amount of the blast cells in the patient D.?

A. <5%;

B. 6-10%;

C. 11-15%;

D. 16-20%;

E.> 21%.


Test answer samples.

2-Е Usually bone marrow can be drawn by sternal puncture or trepine biopsy (iliac bone can be used).


5-А Many of the hemoblastoses may be comprised of several syndromes, some of which are hyperplastic (lymph nodes enlargement, splenomegaly etc.) and intoxication (fever etc.). To verify the diagnosis usually sternal puncture is performed, normal blast cell rate is <5%.


IV. Study plan


The following topic parts should be studied to archive aims listed above:

1. Etiology and pathogenesis.

2. Classification of HL.

3. Methods for clinical and instrumental HL diagnosing.

4. Lymphomas’ differential diagnostics.

5. Treatment of HL.


Literature for studying theoretical aspects of the topic:

  1. Hellman S (2007). "Brief Consideration of Thomas Hodgkin and His Times". in Hoppe RT, Mauch PT, Armitage JO, Diehl V, Weiss LM. Hodgkin Lymphoma (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 3–6. ISBN 0-7817-6422-X.

  2. Hodgkin T (1832). "On some morbid experiences of the absorbent glands and spleen". Med Chir Trans 17: 69–97.

  3. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) http://canques.seer.cancer.gov/cgi-bin/cq_submit?dir=seer2006&db=4&rpt=LINE&sel=1^0^79^0^^^&x=Age%20at%20diagnosis^6,7,8,9,10,11,12,13,14,15,16,17,18,19,20&y=Race^0,1,2^Sex^0,1,2&dec=1&template=null

  4. Fermé C, Eghbali H, Meerwaldt JH, et al. (November 2007). "Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease". The New England Journal of Medicine 357 (19): 1916–27. doi:10.1056/NEJMoa064601. PMID 17989384.

  5. Stein RS, Morgan D (2003). Handbook of cancer chemotherapy (6th ed.). Hagerstown, MD: Lippincott Williams & Wilkins. pp. 493. ISBN 0-7817-3629-3.

  6. "HMDS: Hodgkin's Lymphoma". Retrieved 2009-02

  7. Lectures in hospital therapy.



Short methodic guidelines for the classes on the topic “Hodgkin lymphoma”


First the teacher checks students’ initial knowledge level using initial level tests and corrects it if necessary. Then students examine patients on the topic of the lesson and start detailed discussion of the patients with the teacher. The discussion is followed by the end-level tests. In the end of the lesson the teacher summarizes students’ work on the topic.


Appendix 1

HL logical scheme




Appendix 2

^
Diagnostic algorithm of lymphadenopathy




  1. Hodgkin’s disease;

  2. Infectious mononucleosis;

  3. Chronic lymphatic leukemia;

  4. non-Hodgkin’s lymphomas;

  5. Acute leukemia;



^

Lymphadenopathy syndrome



no

Typical histological findings of the affected lymphatic nodule, наличие клеток Sternberg cells.

Leukocytosis, atypical mononuclears in CBC, enlarged and tender to palpation lymphatic nodes, intoxication, rarely - splenomegaly





есть


yes


no

1

yes




Absolute lymphocytosis, over 30% lymphocytes in bone marrow, diffuse lymphatic hyperplasia in bone marrow biopsy, immune phenotyping data



2


yes


3


no


yes


4

Typical histological findings of the affected lymphatic nodule


нет

yes


no

Over 20% blast cells in bone marrow


5







Appendix 3

^ Histological classification of HL

Nodular sclerosis Hodgkin disease (NSHD) (60-80% of all cases): The morphology shows a nodular pattern. Broad bands of fibrosis divide the node into nodules. The capsule is thickened. The characteristic cell is the lacunar-type Reed-Sternberg cell, which has a monolobated or multilobated nucleus, a small nucleolus, and abundant pale cytoplasm. NSHD is frequently observed in adolescents and young adults and usually involves the mediastinum and other supradiaphragmatic sites.

^ Mixed-cellularity Hodgkin disease (MCHD) (15-30% of cases): Histologically, the infiltrate is usually diffuse. Reed-Sternberg cells are of the classic type (large, with bilobate, double or multiple nuclei, and a large, eosinophilic nucleolus). MCHD commonly affects the abdominal lymph nodes and spleen. Patients with this histology typically have advanced-stage disease with systemic symptoms. MCHD is the histologic type most commonly observed in patients with human immunodeficiency virus (HIV) infection.

^ Lymphocyte-depleted Hodgkin disease (LDHD) (less than 1% of cases): The infiltrate in LDHD is diffuse and often appears hypocellular. Large numbers of Reed-Sternberg cells and bizarre sarcomatous variants are present. It is associated with older age and HIV-positive status. Patients usually present with advanced-stage disease. Epstein-Barr virus (EBV) proteins are expressed in many of these tumors. Many cases of LDHD diagnosed in the past were actually were non-Hodgkin lymphomas, often of the anaplastic large-cell type.

^ Lymphocyte-rich classic Hodgkin disease (LRHD) (5% of cases): In this type of Hodgkin disease (Hodgkin's lymphoma), Reed-Sternberg cells of the classic or lacunar type are observed, with a background infiltrate of lymphocytes. It requires immunohistochemical diagnosis. Some cases may have a nodular pattern. Clinically, the presentation and survival patterns are similar to those for MCHD.

^ Nodular lymphocyte-predominant Hodgkin disease (NLPHD) (5% of cases): In contrast to the other histologic subtypes, the typical Reed-Sternberg cells in NLPHD are either infrequent or absent. Instead, lymphocytic and histiocytic (L&H) cells, or "popcorn cells" (their nuclei resemble an exploded kernel of corn), are seen within a background of inflammatory cells, which are predominantly benign lymphocytes. Unlike Reed-Sternberg cells, L&H cells are positive for B-cell antigens, such as CD19 and CD20, and are negative for CD15 and CD30. A diagnosis of NLPHD needs to be supported by immunohistochemical studies, because it can appear similar to LRHD or even some non-Hodgkin lymphomas.


Appendix 4

HL Staging


The Ann Arbor classification (1971) is used most often for cases of Hodgkin disease (Hodgkin's lymphoma). Clinical staging involves assessment of disease extent by clinical examination, history, and imaging techniques. When staging laparotomies are used as part of staging, the disease extent is designated as pathologic staging.10


^ Stage I denotes a single lymph node area or single extranodal site.


Stage II denotes 2 or more lymph node areas on the same side of the diaphragm.


Stage III denotes lymph node areas on both sides of the diaphragm.


Stage IV denotes disseminated or multiple involvement of the extranodal organs. Involvement of the liver or the bone marrow is considered stage IV disease. For staging classifications, the spleen is considered to be a lymph node area. Involvement of the spleen is denoted with the S suffix (ie, IIBS).


A or B designations denote the absence or presence of B symptoms.

A "B" designation includes the presence of 1 or more of the following:

-Fever (temperature >38°C)

-Drenching night sweats

-Unexplained loss of more than 10% of body weight within the preceding 6 months

An "A" designation is the absence of the above.

An "X" designation is sometimes used to indicate the presence of bulky disease.


^ Summary Test Control

1. Patient I., 16 y. o., complained on the submandibular right side lymph nodes. These lymphatic nodes movable, dense-elastic, not matted with the skin and painless. Clinical blood test and myelogram did not reveal any abnormalities. On biopsy of the affected lymphatic nodes proliferation of mature lymph-and histiocytes, presence of large cells with broad light cytoplasm were observed. Severe sclerosis and focal necrosis wasn’t found.

What disease in this patient?

A. tuberculosis;

B. chronic lymphatic leucaemia;

C. reactive lymphadenitis;

D. Hodgkin’s disease;

I. Acute lymphatic leucaemia


2. Patient K., 56 years old, was admitted to the cardiology department with complaints on shortness of breath during physical activity, cough with sputum. These complaints appeared about a year ago and gradually increased. The general condition of medium gravity. Normal skin color. Above the lower lung lubes on percussion – dull sound, in the same area breath could not be auscultated. Heart rate is regular, the tones did not change, there is no murmur. HR 88 per minute. BP 160/80 mm Hg. ECG: sinus rhythm, a regular, normal position of the electrical axis of heart, HR-84 bpm., Signs of left ventricular hypertrophy.

On X-ray of the chest mediastinal lymphatic nodes enlargement, fluid in the pleural cavity.

What kind of examination would verify the diagnosis in this case?

A. CT of the thorax;

B. Ultrasound examination of the abdominal cavity;

C.Bronchoscopy;

D. peakflowmetry;

E. mediastinotomiy with mediastinal lymph node biopsy.

3. Patient L., 60, complains on the fever up to 38,0 ° C, night sweats, 1 kg body mass loss during the past 2 months.

Physical examination: condition serious. Pale skin, without pathological rash. Front supraclavicular and cervical lymph nodes - up to 1.5 cm, dense, mobile, not matted with the skin, painless. Above the lungs vesicular breathing is auscultated. Heart sounds are muted, systolic murmur on the apex, HR-104 in minutes, regular. BP-140/90 mm Hg. Abdomen soft, smooth. Lower margin of the spleen can be palpated. Supraclavicular lymph node biopsy: growth of dense connective tissue with the deposition of amorphous protein masses, among which are small clusters of fibroblasts, Hodgkin's , Shternberg cells were found.

What histological type of HD occured in the patient?

A. lymphoid predominance (paragranulome);

B. limfohistiocytory;

C. nodular sclerosis;

D. mixed-cellularity;

E. lymphoid depletion.


4. In the patient M., 62 years old, according to characteristic histological changes of enlarged lymphatic nodes in the supraclavicular area (the only peripheral) HD was diagnosed. Specify the additional studies needed to determine the stage of disease in this patient?

A.CBC, bone marrow aspiration;

B. bone marrow aspiration, trephine biopsy;

C. CT of the chest and abdominal cavities , spine, ribs, pelvic bones X-ray;

D. ultrasonography of liver, spleen;

E. Gastroduodenoscopy.


5. Patient I., 64 years, during 4 years is observed by hematologist with the diagnoses of HD. He has been admitted to the hospital with complaints on fever up to 38,8 C night swears, the loss of 10 kg body mass during the past 6 months, the skin. General condition is critical. Pale skin, with scratch traces. Enlarged submandibular lymphatic on both sides, not matted with the surrounding tissue, painless. No changes in the rest of the peripheral lymphatic nodes were found. Additional studies: mesenteric lymph nodes enlargement

Determine the stage of the disease.

A. II A;

B. II B;

C. III A;

D. III B;

E. IVA.


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