Lymphoreticular by IHC001

Lymphoreticular Pathology

Summary of Presentation • Topic 1 – Granulomatous lymphadenitis • Topic 2 – Reactive and neoplastic lymph node histology • Topic 3 – Lymphoma histology • Topic 4 – Lymphoma genetics • Topic 5 – Extranodal lymphoma • Aspects of these topics will be covered through the following EMQs and MCQs.

TOPIC 1 GRANULOMATOUS LYMPHADENITIS

EMQ question A1 • For each of the following scenarios, select the most likely condition from the list of options • A 35 year old woman develops enlarged left axillary lymph nodes. Excision biopsy shows serpiginous necrosis containing nuclear debris and surrounding palisaded histiocytes. A WarthinStarry stain is positive. A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

EMQ question A1 - answer A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p42

Cat Scratch Disease • Usually presents with a skin lesion (7 to 12 days after contact) • Enlargement of regional lymph nodes, usually cervical and axillary • Early changes: Follicular hyperplasia, histiocytic proliferation, monocytoid B-cell hyperplasia • Intermediate: granulomatous • Late: abscesses with central stellate necrosis with neutrophils and a surrounding palisade of histiocytesGramnegative, pleomorphic, extra-cellular coccobacillus Bartonella henselae • Warthin-Starry silver stain – singly, small clumps or chains in necrotic foci • Can be confirmed by serology, IHC or PCR

Cat Scratch Disease

Cat scratch disease

Suppurative Lymphadenitis • Yersinia – terminal ileal disease with mesenteric node involvement • Lymphogranuloma venereum (Chlamydia trachomatis) – genital lesion followed by inguinal lymphadenopathy • Tularaemia (Francisella tularensis) – transmitted by ticks • Rare causes – Listeria monocytogenes, Pseudomonas mallei and pseudomallei, Corynebacterium ovis, pyogenes and ulcerans

EMQ question A2 • For each of the following scenarios, select the most likely condition from the list of options • A 24 year old woman presents with cervical lymphadenopathy. Lymph node histology shows follicular hyperplasia, monocytoid B-cell hyperplasia and small aggregates of epithelioid cells, some of which encroach on germinal centres. A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

Emq question A2 - answer A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p22-3

Toxoplasmosis • Young women, posterior cervical lymph nodes • Triad: – Follicular hyperplasia with intense mitotic activity and phagocytosis of nuclear debris, – Monocytoid B-cell hyperplasia in the sinuses, – Small clusters of epithelioid cells (granulomas) encroaching on germinal centres.

• Immunoblasts and plasma cells in medullary cords • Toxoplasma pseudocysts very rare in nodes • Protozoa Toxoplasma gondii (difficult to see)

Toxoplasmosis – small non-caseating granulomas

Toxoplasmosis – monocytoid B cells

EMQ question A3 • For each of the following scenarios, select the most likely condition from the list of options • A 55-year old man presented with weight loss, fever and polyarthralgia. An abdominal CT scan showed mesenteric and retroperitoneal lymphadenopathy. A laparoscopic lymph node biopsy shows collections PASD-positive mononuclear and multinucleated histiocytes with foamy cytoplasm. A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

Emq question A3 answer A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p35

Whipple’s Disease • Rare systemic disease • Classic presentation - wasting illness, arthralgias, arthritis, fever and diarrhoea. Lymphadenopathy may be present. If small intestine affected, steatorrhoea often present. • Gram-positive bacterium, Tropheryma whippelii • Lipogranulomatous lymphadenitis, sinuses filled with foamy PASD-positive histiocytes

Whipple’s Disease

Differential diagnosis Lipogranulomatous lymphadenitis • Lymphangiogram effect – due to lipid rich contrast medium • Long term total parenteral nutrition Infective lymphadenitis • M. avium intracellulare – Ziehl Neelsen positive • Fungal infection e.g. histoplasmosis – Grocott positive

EMQ question A4 • For each of the following scenarios, select the most likely condition from the list of options • A 30-year old woman presents with shortness of breath, a dry cough, weight loss and cervical lymphadenopathy. An excisional lymph node biopsy shows discrete non-necrotising granulomas with focal fibrosis. A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

EMQ question A4 - answer A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p40-1

Sarcoidosis • Chronic granulomatous disease of unknown aetiology • Multisystem involvement – lungs commonest • Small granulomas of epithelioid cells with occasional Langhans giant cells and absent or limited necrosis • Non-specific inclusion bodies

Sarcoidosis

Sarcoidosis Asteroid body

Schaumann body

Hamazaki-Wesenberg bodies

EMQ question A5 • For each of the following scenarios, select the most likely condition from the list of options • A 75-year old diabetic smoker presents with cough, fever and weight loss. Lymph node biopsy shows granulomas with areas of central necrosis. Staining with PASD and Grocott is positive. A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

EMQ question A5 - answer A Toxoplasmosis

G Berylliosis

B Amoebiasis

H Histoplasmosis

C Tuberculosis

I Whipple’s disease

D Cat scratch disease

J Leprosy

E Crohn’s disease

K Leishmaniasis

F Yersinia

L Sarcoidosis

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p40

Histoplasmosis • Symptoms usually in immunocompromised • Acute pulmonary, chronic pulmonary, progressive disseminated forms • Histological features – Necrotising granulomas – like tuberculosis – Sinus histiocytosis – Histiocytes containing encapsulated budding yeasts

• Other systemic mycotic infections involving lymph nodes: – Cryptococcosis, coccidioidomycosis and blastomycosis

Histoplasmosis

Histoplasma capsulatum

Granulomatous Lymphadenitis Useful references 1.Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, 3547 2.Rosai and Ackerman’s Surgical Pathology, 9th ed; Rosai J (ed); Mosby: 2004 vol 2,1895-1900, 1916-7

TOPIC 2 REACTIVE AND NEOPLASTIC LYMPH NODE HISTOLOGY

MCQ Question 1 • A 20-year old Asian woman presents with painful enlarged lymph nodes in the neck, fever and flu-like symptoms. Lymph node biopsy shows widespread apoptosis and necrosis with paracortical expansion by blast cells and histiocytes with crescentic nuclei. • What is the most likely diagnosis? A. B. C. D. E.

Kikuchi’s disease Diffuse large B-cell lymphoma Kimura’s disease Cat scratch disease Infectious mononucleosis

MCQ Question 1 A. Kikuchi’s disease B. Diffuse large B-cell lymphoma C. Kimura’s disease D. Cat scratch disease E. Infectious mononucleosis Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p28,32

Kikuchi’s disease • Necrotising lymphadenitis/Kikuchi-Fujimoto disease • Particularly in Japan and other Asian countries • Young women mostly affected • Idiopathic and self-limited • 3 histological stages – proliferative – necrotising – xanthomatous

Kikuchi’s disease • • • •

Paracortical necrosis (without neutrophils) Apoptosis with karyorrhectic debris Plasmacytoid monocytes Phagocytic histiocytes with crescentic nuclei • T-cell immunoblasts

Kikuchi’s disease

MCQ Question 2 • A 27-year old man is noted to have mediastinal widening on an occupational chest x-ray. Neck palpation reveals occasional enlarged lymph nodes, biopsy of which reveals sclerotic interfollicular bands with vascularised follicles surrounded by broad concentric mantle zones. • What is the most likely diagnosis? A. B. C. D. E.

Nodular sclerosis Hodgkin’s lymphoma Kimura’s disease Nodular lymphocyte predominant Hodgkin’s lymphoma Castleman’s disease Mantle cell lymphoma

MCQ Question 2 A. B. C. D. E.

Nodular sclerosis Hodgkin’s lymphoma Kimura’s disease Nodular lymphocyte predominant Hodgkin’s lymphoma Castleman’s disease Mantle cell lymphoma

Reference

•

Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p20

Castleman’s Disease • Three categories – hyaline vascular, plasma cell variant, multicentric • Hyaline vascular – commonest type, usually solitary – occurs in young adults – usually in mediastinum – Histology • Broad concentric onion-skin mantle zone • Hyalinised and vascularised follicle centres • Interfollicular areas hyalinised and vascularised

Hyaline Vascular Castleman’s disease

Hyaline vascular Castleman’s disease

EMQ question B1 • Match the following description with the appropriate disorder: • A 4-year old boy presents with a fever, cough and a red blotchy skin rash. A lymph node biopsy shows characteristic giant cells with multiple clustered and overlapping nuclei. A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

Emq question b1 - answer A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p27

Measles lymphadenitis • Related to infection or vaccination • Involvement of nodal and extranodal lymphoid tissue • Histology – Follicular hyperplasia – Paracortical proliferation of immunoblasts – Relative depletion of lymphocytes – Warthin-Finkeldey giant cells

Warthin-Finkeldey giant cells

EMQ question B2 • Match the following description with the appropriate disorder: • A 14-year old male presents with fever, night sweats and cervical lymphadenopathy. Lymph node biopsy shows sinus expansion by histiocytes, some of which contain engulfed lymphocytes. A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

EMQ question B2 - answer A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p34

Rosai-Dorfman Disease • ‘Sinus histiocytosis with massive lymphadenopathy’ • Children and young adults • Usually cervical lymphadenopathy and may have systemic symptoms • Histology – Prominent sinus histiocytosis – Lymphophagocytic histiocytes – emperipolesis – Numerous plasma cells in medullary cords

Rosai-Dorfman Disease

Emperipolesis

EMQ question B3 • Match the following description with the appropriate disorder: • A 33-year old man presents with enlarged cervical and axillary lymph nodes. Lymph node biopsy shows a nodular growth pattern with large cells containing multilobated nuclei that stain with CD20 but not CD15 or CD30. A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

EMQ question B3 - answer A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p118

Nodular Lymphocyte Predominant Hodgkin’s Lymphoma • Peak incidence in fourth decade, male predominance • Most present with enlarged cervical, axillary or inguinal nodes • Synchronous/metachronous association with progressive transformation of germinal centres • Histology – Irregularly sized, mottled nodules – Popcorn/L&H cells – positive for CD45, CD20, CD79a; negative for CD15 and CD30 (usually) – Plasma cells uncommon, neutrophils and eosinophils not a feature

Nodular lymphocyte predominant Hodgkin’s lymphoma

Popcorn Cell with T-cell Rosette

EMQ question B4 • Match the following description with the appropriate disorder: • A 30-year old man presented with episodes of pruritis, flushing and syncopal attacks. Maculopapular skin lesions were noted, which showed wealing on rubbing. Biopsy of an enlarged lymph node showed an infiltrate of cells with indented nuclei and abundant clear cytoplasm with granules that stain positively with toluidine blue. A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

EMQ question B4 - answer A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p136

Indolent systemic mastocytosis • One of seven WHO categories of mastocytosis – all uncommon • Urticaria pigmentosa-like skin lesions • Darier’s sign – dermal oedema and erythema on rubbing • Histology – Mast cell infiltrate – indented nuclei, abundant pale cytoplasm, may be spindle cells – Often numerous eosinophils – Granules stain with toluidine blue and mast cell tryptase

Mastocytosis

Toluidine Blue

EMQ question B5 • Match the following description with the appropriate disorder: • A 2-year old boy presents with widespread scaling erythematous plaques on the skin, hepatosplenomegaly and lymphadenopathy. Lymph node biopsy shows distention of the sinuses by cells with grooved nuclei and abundant pale eosinophilic cytoplasm which stain positively with S100 and CD1a. A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

EMQ question B5 - answer A Measles

G Mastocytosis

B Follicular dendritic sarcoma

H CMV infection

C Castleman’s disease

I Anaplastic large cell lymphoma

D Infectious mononucleosis

J Langerhans cell histiocytosis

E Nodular lymphocyte predominant Hodgkin’s lymphoma

K Rosai-Dorfman disease

F Myeloid sarcoma

L Nodular sclerosis Hodgkin’s lymphoma

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p133

Langerhans cell histiocytosis • Initially divided into eosinophilic granuloma, Hand-Schüller-Christian disease and LettererSiwe disease • All ages but peak incidence 1 – 3 years • Localised or multisystem • Histology – Infiltrate of Langerhans cells – complex nuclei with long nuclear folds/grooves, abundant pale eosinophilic cytoplasm – Positive for S100 and CD1a – Birbeck granules seen ultrastructurally – Eosinophils often abundant but not always present

Langerhans cell histiocytosis

Birbeck granule

Reactive and Neoplastic lymph node histology Useful references 1.Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006 2.Rosai and Ackerman’s Surgical Pathology, 9th ed; Rosai J (ed); Mosby: 2004 vol 2

TOPIC 3 LYMPHOMA HISTOLOGY

MCQ Question 3 • A 25–year old man presents with firm, non-tender cervical lymphadenopathy. Lymph node biopsy shows a nodular growth pattern of small lymphocytes with very scanty eosinophils and neutrophils. Collagen bands are not evident. Scattered large mono- and bi-nucleate cells are present (CD15+ and CD30+). • What is the most likely diagnosis? A. B. C. D. E.

Nodular sclerosis Hodgkin’s lymphoma Nodular lymphocyte predominant Hodgkin’s lymphoma Lymphocyte rich Hodgkin’s lymphoma Lymphocyte depleted Hodgkin’s lymphoma Mixed cellularity Hodgkin’s lymphoma

MCQ Question 3 A. B. C. D. E.

Reference

•

Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p126-8

Lymphocyte rich classical Hodgkin’s lymphoma • Approximately 5% of classical Hodgkin’s lymphoma (CHL) • Previously often misdiagnosed as NLPHL • Associated with EBV in 40% of cases • Histology – Usually nodular growth with small inactive germinal centres – Predominantly small lymphocytes – No sclerosis – Absent/scanty neutrophils and eosinophils – Scattered Reed-Sternberg/Hodgkin cells

Lymphocyte rich classical Hodgkin’s lymphoma

MCQ Question 4 • A 62-year old man presents with fever, night sweats, weight loss and lymphadenopathy. Lymph node biopsy shows complete effacement of the nodal architecture by large cells with prominent nucleoli that stain positively with CD20, CD79a, Bcl-2, Bcl-6 and are negative for CD30 and TdT. • What is the most likely diagnosis? A. B. C. D. E.

Burkitt’s lymphoma Diffuse large B-cell lymphoma Anaplastic large cell lymphoma Lymphocyte-depleted Hodgkin’s lymphoma Lymphoblastic lymphoma

MCQ Question 4 - answer A. B. C. D. E.

Burkitt’s lymphoma Diffuse large B-cell lymphoma Anaplastic large cell lymphoma Lymphocyte-depleted Hodgkin’s lymphoma Lymphoblastic lymphoma

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p80-5

Diffuse large B-cell lymphoma • 4 subtypes – centroblastic, immunoblastic, Tcell rich large B-cell, anaplastic • De novo or from transformation of low grade lymphoma (Richter syndrome – CLL) • Histology – Tumour cells ≥2x small lymphocyte size – Variable sclerosis – Positive for CD20, CD79a, Bcl-6 and variably CD10 and Bcl-2 – CD30+ in anaplastic variant

Diffuse Large B-cell Lymphoma

DLBCL – anaplastic variant

Mcq Question 4 - answer A. B. C. D. E.

Burkitt’s lymphoma Diffuse large B-cell lymphoma Anaplastic large cell lymphoma Lymphocyte-depleted Hodgkin’s lymphoma Lymphoblastic lymphoma

Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p80-5

Lymphoma Histology Useful references 1.Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006 2.Rosai and Ackerman’s Surgical Pathology, 9th ed; Rosai J (ed); Mosby: 2004 vol 2

TOPIC 4 LYMPHOMA GENETICS

EMQ question C1 • Match the following chromosomal abnormalities with the appropriate disorder: • t2:5

A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

EMQ question C1 - answer A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

Reference

• Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p96

Alk+ Anaplastic Large Cell Lymphoma • Translocations involve anaplastic lymphoma kinase (ALK) gene on chr. 2 and: • t(2;5)(p23;q35) nucleophosmin (NPM) in common variant (70-80%) • t(1;2)(q25;p23) – tropomysin 3 (TPM3) in 10-20% • Less common – t(2;3), Inv2, t(2;17)

EMQ question C2 • Match the following chromosomal abnormalities with the appropriate disorder: • t8:14 A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

EMQ question C2 - answer A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

Reference

• Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p87

Burkitt’s Lymphoma • Translocations involve c-MYC locus on chr. 8 and one of the immunoglobulin genes • t(8;14)(q24;q32)– Ig heavy chain (60-70%) • t(8;22)(q24;q11) – Ig λlight chain (10-15%) • t(2;8)(p12;q24) – Ig κ light chain (2-5%)

EMQ question C3 • Match the following chromosomal abnormalities with the appropriate disorder: • t11:14

A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

EMQ question C3 - answer A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

Reference

• Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p77

Mantle Cell Lymphoma • BCL-1 (cyclin D1) on chr. 11 and IgH on chr. 14 • t(11;14)(q13;q32) in 5070% • Also in 10-20% in Bprolymphocytic leukaemia, plasma cell leukaemia, 2-5% chronic lymphocytic leukaemia and in multiple myeloma Cyclin D1

EMQ question C4 • Match the following chromosomal abnormalities with the appropriate disorder: • t9:22

A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

EMQ question C4 - answer A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

Reference • Robbins and Cotran Pathologic Basis of Disease, 7th ed; Kumar V, Abbas AK, Fausto N (eds); Elsevier Saunders: 2005, p697-8

Chronic Myelogenous Leukaemia • t(9;22)(q34;q11) • ABL on chr. 9 and BCR on chr. 22 – Philadelphia chromosome • Also in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL)

EMQ question C5 • Match the following chromosomal abnormalities with the appropriate disorder: • t14:18

A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

EMQ question C5 - answer A Follicular lymphoma

G Lymphoplasmacytic lymphoma

B Mantle cell lymphoma

H Chronic myelogenous leukaemia

C Chronic lymphocytic leukaemia

I Angioimmunoblastic lymphoma

D Hairy cell leukaemia

J Anaplastic large cell lymphoma

E Burkitt’s lymphoma

K Nodular lymphocyte predominant Hodgkin’s lymphoma

F MALT lymphoma

L Hepatosplenic T-cell lymphoma

Reference

•

Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p71-2

Follicular Lymphoma • IgH gene on chr. 14 and BCL-2 on chr. 18 • t(14;18)(q32;q21) in 70-80% • Also in 20-30% of diffuse large B-cell lymphoma and 1-2% of B-CLL

BCL-2

Lymphoma Genetics Useful references 1. http://atlasgeneticsoncology.org/index.html 2. Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006 3. Rosai and Ackerman’s Surgical Pathology, 9th ed; Rosai J (ed); Mosby: 2004 vol 2 4. Robbins and Cotran Pathologic Basis of Disease, 7th ed; Kumar V, Abbas AK, Fausto N (eds); Elsevier Saunders: 2005

TOPIC 5 EXTRANODAL LYMPHOMA

MCQ Question 5 • A 65-year old woman has a 7-month history of nausea, epigastric discomfort and weight loss. Gastric biopsy shows a monomorphic lymphocytic infiltrate in the lamina propria with infiltration of gastric glands by atypical lymphocytes. Curvilinear bacterial rods are present in the surface mucus. • What is the most likely condition?

A. B. C. D. E.

Mantle cell lymphoma Follicular lymphoma MALT lymphoma Chronic lymphocytic lymphoma Lymphoplasmacytic lymphoma

MCQ Question 5 - answer A. Mantle cell lymphoma B. Follicular lymphoma C. MALT lymphoma D. Chronic lymphocytic lymphoma E. Lymphoplasmacytic lymphoma Reference • Rosai and Ackerman’s Surgical Pathology, 9th ed; Rosai J (ed); Mosby: 2004 vol 2, p1945-6

MALT lymphoma • Low grade small B-cell lymphoma • Majority of gastric MALToma due to H. pylori infection • Lymphoepithelial lesions • CD20 and CD79a positive • CD5, CD10 and CD23 negative • May regress after treatment of H. pylori

MCQ Question 6 • A 60-year old woman presents with generalised painless lymphadenopathy. A previous diagnostic lymph node biopsy was performed. Now a bone marrow trephine biopsy shows nodular paratrabecular infiltrates of small lymphoid cells. • What is the most likely diagnosis?

A. B. C. D. E.

Chronic lymphocytic lymphoma Mantle cell lymphoma Follicular lymphoma Hairy cell leukaemia Lymphoplasmacytic lymphoma

MCQ Question 6 - answer A. Chronic lymphocytic lymphoma B. Mantle cell lymphoma C. Follicular lymphoma D. Hairy cell leukaemia E. Lymphoplasmacytic lymphoma Reference

• Rosai and Ackerman’s Surgical Pathology, 9th ed; Rosai J (ed); Mosby: 2004 vol 2, p2080

Follicular lymphoma • Commonest subtype of low grade NHL • Usually presents with lymphadenopathy, bone marrow and spleen involvement common • Derived from follicle centre B-cells. Varying proportions of centrocytes and centroblasts • Grading: – Grade 1 - >5 blasts/HPF – Grade 2 – 6-15 blasts/HPF – Grade 3 - >15 blasts/HPF

• Bone marrow trephine – paratrabecular nodules virtually diagnostic

Follicular Lymphoma

MCQ Question 7 • A 40–year old man presents with an acute abdomen and an emergency laparotomy is performed during which a segment of ulcerated and perforated jejunum is excised. The bowel wall is diffusely infiltrated by intermediate to large cells with irregular nuclei and prominent nucleoli. Post-operative serology reveals a raised IgA tissue transglutaminase antibody. • What is the most likely diagnosis? A. B. C. D. E.

Diffuse large B-cell lymphoma Anaplastic large cell lymphoma Enteropathy-associated T-cell lymphoma Mixed cellularity Hodgkin’s lymphoma MALT lymphoma

MCQ Question 7 - answer A. Diffuse large B-cell lymphoma B. Anaplastic large cell lymphoma C. Enteropathy-associated T-cell lymphoma D. Mixed cellularity Hodgkin’s lymphoma E. MALT lymphoma Reference • Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006, p108-9

Enteropathy-associated T-cell lymphoma • Closely associated with Coeliac disease – may be clinically occult • High grade lymphoma with very poor prognosis • Histology – Mucosal changes – intra-epithelial lymphocytosis, villous atrophy – Infiltrate of pleomorphic cells diffusely involves small bowel wall and lymph nodes – Positive for CD3, CD7 and variably CD30

Enteropathy-associated T-cell lymphoma

Extranodal Lymphoma Useful references

1.Diagnostic lymph node pathology; Wright DH, Addis BJ, Leong AS; Hodder Arnold: 2006 2.Rosai and Ackerman’s Surgical Pathology, 9th ed; Rosai J (ed); Mosby: 2004 vol 2 3.Robbins and Cotran Pathologic Basis of Disease, 7th ed; Kumar V, Abbas AK, Fausto N (eds); Elsevier Saunders: 2005

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