Lymphoid Malignancies

What are the key components of the lymphatic system?

Lymph nodes

Spleen

Thymus

Bone marrow

Tonsils

What is the overall function of LNs?

Bean-shaped organs

Filter lymph:

• Cervical

• Axillary

• Inguinal

• Mediastinal

• Abdominal regions

What is the overall function of the spleen?

Filters blood

Stores/Makes lymphocytes

Store RBCs

Largest lymphoid organ

What is the overall function of the thymus?

Site of T-lymphocyte maturation and multiplication

What is the overall function of the bone marrow?

Produce WBCs, RBCs, platelets

Site of B-cell development

What is the overall function of the tonsils?

Bilateral lymphoid structures at lateral oropharynx

Mucosal immunity

What is the current classification system for lymphoma?

WHO 5th edition

Categorizes by cell of origin:

• Precursor B

• Mature B

• Precursor T

• Mature T

• NK cells

What are the different types of lymphoma?

Hodgkin Lymphoma (HL)

Non-Hodgkin Lymphoma (NHL)

Indolent vs. Aggressive NHL

What is the cell origin for Hodgkin Lymphoma?

Aberrant mature B-cells (only)

What distinct cells are present in Hodgkin Lymphoma (HL)?

Reed-Sternberg cells

• Start in single node/chain; contiguous spread

What is the cell origin for Non-Hodgkin Lymphoma?

90% B cells

10% T/NK-cell

Frequently extranodal, contiguous spread

What percentage of NHL cases are aggressive?

60% of NHL cases

What percentage of NHL cases are indolent?

40% of NHL cases

• Slow-growing, fewer symptoms at diagnosis

What is the normal appearance of a LN?

Kidney bean-shaped with fatty hilum

Soft texture'; Tan-brown or tan-pink

Smooth, glistening capsule

Up to 1 cm in short axis normally

What is lymphadenopathy?

The medical term for swollen or enlarged LNs

What is the normal appearance of reactive lymph nodes?

Soft

Tan-brown

May show focal necrosis

What is the neoplastic appearance of LNs?

Rounded, expanded - loss of kidney-bean shape

Tan-white

Fleshy

Homogenous cut surface

Consistency soft → Firm depending on fibrous

What is the neoplastic appearance of nodular sclerosis CHL?

Nodules separated by:

• Thick fibrous bands

• Thicken capsule

What is the neoplastic appearance of follicular lymphoma?

Nodular cut surface

What is the neoplastic appearance of metastatic carcinoma?

White

Firm, gritty

Necrotic

± Cystic spaces (papillary thyroid or teratoma involvement)

What is the standard grossing protocol for LNs?

Measure 3D

Sections at 2-3 mm intervals along long axis

Touch preps before fixation (air-dried or alcohol-fixed)

RPMI for flow cytometry/cytogenetics

• Extra for lymphoma

10% NBF fixation (6-72 hours)

Entirely submit nodes < 5 cm

• Consult pathologist if > 5 cm

B-Plus or B5 fixative may be used

Why are touch preparations made before fixation?

To preserve cellular detail for:

• Cytology

• Flow cytometry triage

• FISH

• Rapid preliminary diagnosis

What medium should fresh lymphoma tissue be placed in for flow cytometry?

RPMI medium

What is the standard grossing protocol for a spleen?

Weigh and measure in 3D

Describe capsule integrity

Inspect hilar fat for:

• Splenic artery aneurysm

• LNs

• Accessory splenules

Serially section

Fresh → Touch preps

RMPI → Flow/Cytogenetics

Submit representative sections:

• Lesion

• Uninvolved spleen with capsule

Identify, describe, and submit all hilar LNs

What should be described for the serial sections of the spleen?

Describe cut surface:

• Color

• Texture

• Congestion

• Infarcts

• Nodules

What should be described for the capsule integrity of the spleen?

Intact vs. defects from surgery/tumor/trauma

What margin should be included on a traumatic spleen?

Vascular margin

What margins are needed for confirmed lymphoma in a spleen?

No need for margins

What splenic pattern is commonly seen in CLL/SLL?

Diffuse miliary white nodules

What is splenomegaly?

Abnormal enlargement of the spleen

What is an accessory spleen?

A congenital focus of ectopic splenic tissue

What is a splenic infarct?

Area of ischemic necrosis caused by vascular occlusion

What are the different lymphomas present in the spleen?

Low-grade lymphoma — Miliary pattern

High-grade lymphoma — Nodular pattern

Diffuse involvement

What is the common distribution of low-grade lymphoma — miliary pattern?

Diffuse

Innumerable pinpoint white nodules throughout parenchyma

Submit up to 5 representative sections

Miliary pattern is characteristic of what kind of lymphoma?

Indolent/Low-grade splenic lymphoma

What is the common distribution of high-grade lymphoma — nodular pattern?

Single large nodule or multiple large discrete masses

Submit 1 section per cm of greatest dimension of each mass

Nodular pattern is characteristic of what kind of lymphoma?

Aggressive lymphomas (DLBCL, classical HL)

What does DLBCL stand for?

Diffuse large B-cell lymphoma

What is the common distribution of diffuse involvement?

Diffuse replacement of splenic parenchyma

Hilary LNs frequently involved

Entirely submit all

Diffuse involvement is characteristic of what kind of lymphoma of the spleen?

CLL/SLL

Other systemic diseases

What does CLL stand for?

Chronic lymphocytic leukemia

What does SLL stand for?

Small lymphocytic lymphoma

What differentiates between CLL and SLL?

One occurs in bone marrow, blood

The other occurs in the lymphatic system

What are the block allocation for the spleen?

Nodule → Capsule

Nodule → Uninvolved parenchyma

Nodule(s) 1 section/cm

Uninvolved parenchyma + capsule

All hilar LNs

What is important when reviewing a splenic infarct?

Patient history

What is the standard grossing protocol for a bone marrow core bx?

Measure L x D

Acceptable quality: ≥1.5 cm

No aspiration artifact

Touch prep before fixation

Formalin (preferred) → IHC, FISH, molecular

Decalcify 45-60 min (10% formic acid)

Avoid over-decalcification → Poor morphology

Submit core entirely after decal

Why should aspiration artifact be minimized?

It reduces evaluation of marrow architecture

Why is formalin preferred for bone marrow core biopsies?

Compatible with:

• Immunohistochemistry (IHC)

• FISH

• Molecular testing

What decalcification method is preferred for bone marrow cores?

10% formic acid for 45–60 minutes

What is a consequence of over-decalcification?

Poor morphology and degraded molecular studies

Which decalcification agent best preserves nucleic acids?

EDTA

What type of bone marrow does NOT require decalcification?

Bone marrow aspirates

Why are touch preparations especially valuable in bone marrow specimens?

Provide immediate cytologic detail before permanent sections

Which touch preparations are optimal for FISH studies?

Air-dried preparations

What is the standard grossing protocol for a bone marrow aspirate and clot?

Describe dimensions and appearance

Peripheral blood smears prepared on clinical side

Remainder in EDTA for FFPE cell block

Aspirate clot: Entirely submit in cassette

Wrap fragmented clot in BioWrap

Aspirate do NOT require decalcification

Sterile technique if cytogenetics requested

What is the standard grossing protocol for a bone marrow touch prep?

Made before fixation from fresh tissue

Touch slide to cut surface or roll core across slide

Air-dry or fix in 95% ethanol

Air-dried preps: Optimal for FISH

Provides immediate cytologic details

Provisional diagnosis pending permanent section

Useful for guiding ancillary test triage

What are the different types of Hodgkin Lymphoma?

Nodular sclerosis (NS-CHL): ~65%

Mixed cellularity (MC-CHL): 20-25%

Lymphocyte-rich (LR-CHL): ~5%

Lymphocyte-depleted (LD-CHL): <2%

What does NS-CHL stand for?

Nodular sclerosis classical Hodgkin Lymphoma

What cell type gives rise to Hodgkin lymphoma?

Mature B cells

What percentage of Hodgkin lymphoma is classical Hodgkin lymphoma?

Approximately 95%

Which Hodgkin lymphoma subtype is most associated with mediastinal masses?

Nodular sclerosis CHL

Which Hodgkin lymphoma subtype lacks sclerosis?

Mixed cellularity CHL

Which classical Hodgkin lymphoma subtype is associated with HIV infection?

Lymphocyte-depleted CHL

Which subtype has the most aggressive gross appearance?

Lymphocyte-depleted CHL

Which Hodgkin lymphoma subtype shows predominantly T lymphocytes in the background?

Lymphocyte-rich CHL

What group is more suspectable to NS-CHL?

Female predominance

What is the gross description of NS-CHL?

Nodules of abnormal tissue divided by thin-to-thick fibrotic bands

Firm consistency

What group is more suspectable to MC-CHL?

Bimodal incidence (pediatric and elderly)

What is the gross description of MC-CHL?

Diffuse

Fleshy, tan-white

Less fibrous than NS

Hilar adenopathy common

What group is more suspectable to LR-CHL?

Ages 30-50

Male predominance

What is the gross description of LR-CHL?

Homogenous, fleshy cut surface

Relatively uniform appearance

What group is more suspectable to LD-CHL?

Median age 30-40 age

Male predominance

What is the gross description of LD-CHL?

Bulky, fibrotic necrotic areas

Most aggressive gross appearance

What is the most common adult leukemia (W)?

Chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL)

What is the most rare/aggressive B-cell lymphoma?

Burkitt lymphoma

What is the most common NHL?

Diffuse Large B-Cell Lymphoma (DLBCL)

What percentage of NHLs arise from B cells?

Approximately 90%

What is the gross appearance of DLBCL?

Rapidly enlarging nodes

Tan-white

Fleshy

Homogeneous

Frequent necrosis

What are common extranodal sites of DLBCL?

GI tract

CNS

Testes

Eye

What lymphoma may transform into DLBCL?

Follicular lymphoma

What gross feature characterizes follicular lymphoma?

Nodular cut surface — Neoplasm appearance

Tan-white

Less fleshy than DLBCL

Rubbery consistency

What genetic abnormality is classically associated with follicular lymphoma?

BCL2 overexpression

What splenic appearance is characteristic of CLL/SLL?

Miliary white nodules

What is the overall gross appearance of CLL/SLL?

Uniform

Homogenous tan-gray nodes

Which lymphoma commonly involves the GI tract as lymphomatous polyposis?

Mantle cell lymphoma

Which lymphoma is associated with H. pylori infection?

MALT lymphoma

What autoimmune diseases predispose to MALT lymphoma?

Sjögren syndrome

Hashimoto thyroiditis

What is the gross appearance of Mantle Cell Lymphoma?

Diffuse nodal enlargement

Firm-fleshy cut surface

What is the gross appearance of Burkitt Lymphoma?

Gray-white fleshy cut surface

Necrosis common

What is the gross appearance of Extranodal Marginal Zone/MALT Lymphoma?

Pale, rubbery mucosal thickening

Which type of NHL has an excellent prognosis/low recurrance?

Extranodal Marginal Zone/MALT Lymphoma

Which type of lymphoma can transform into DLBCL?

Follicular lymphoma

What are the different types of Non-Hodgkin Lymphoma?

DLBCL: 25-30% of NHL

Follicular: ~20% of B-cell NHL

CLL/SLL: Most common leukemia

Mantle cells: ~6% of NHL

MALT: ~7% of all lymphoma

Burkitt: Rare, most aggressive B-cell

What other disease can you find miliary apperance?

Tuberculosis

What is the most common lymphoma involving the tonsil?

Primary B-cell Non-Hodgkin lymphoma

What gross appearance suggests tonsillar lymphoma?

Diffuse enlargement

Homogeneous tan-white fleshy tissue

Loss of crypt architecture

What group is more likely to get tonsillar lymphoma?

Peak incidence is 50-70 years old

What gross appearance suggests recurrent tonsillitis?

Tan-pink rubbery tissue

Distended crypts

Necrotic debris

What gross appearance suggests tonsillar squamous cell carcinoma?

Unilateral mass

Firm

Gray-white

Ill-defined invasive borders

What virus is strongly associated with tonsillar squamous cell carcinoma?

Human papillomavirus infection (HPV)