NON NEOPLASTIC LYMPHADENOPATHY

MODERATOR : DR. RAJESHPRESENTER : DR. ASHWINI K.T

Histology Capsule 3 major parts –1.cortex 2. paracortex 3. medulla1. Cortex – below the capsule ,contains

largest number of follicles.2. Medulla – rich in arteries , veins and a

minor lymphocytic component.3. Paracortex – between cortex and medulla

, contains mobile pool of t-lymphocytes

NODE EXAMINATION: GUIDELINES AND BASIC TECHNIQUES Nodes are cut across the long axis.

Embedded in blocks should not exceed 3mm

In the past, fixatives -mercuric chloride (i.e., B5 fixative) were used

Neutral buffered formalin and zinc formalin solutions are acceptable.

Sections should be 5µm or less.

Sections stained with hematoxylin and eosin (H&E)

CLASSIFICATION I . LYMPHADENITIDES :

1. VIRAL LYMPHADENITIDES 2. BACTERIAL

LYMPHADENITIDES 3. MYCOBACTERIAL

LYMPHADENITIDES 4. FUNGAL LYMPHADENITIDES 5. PROTOZOAL

LYMPHADENITIDES

II . LYMPHADENOPATHIES :

1. REACTIVE LYMPHADENOPATHIES 2. LYMPHADENOPATHY ASSOCIATED

WITH CLINICAL SYNDROMES 3. IATROGENIC LYMPHADENOPATHY 4. VASCULAR LYMPHADEOPATHY5. FOREIGN BODY

LYMPHADENOPATHIES

LYMPHADENITIDES 1. VIRAL LYMPHADENITIDES

INFECTIOUS MONONUCLEOSIS :

Caused by Epstein-Barr virus (EBV)

Clinical Features : Most patients are adolescents and young adults TRIAD : fever, pharyngitis, and cervical lymphadenopathy

PERIPHERAL BLOOD SMEAR :

Atypical lymphocytes (Downey cells) These are transformed lymphocytes

(immunoblasts) with abundant bluish, “pleated” cytoplasm and large, nucleolated nuclei

Giemsa stain.

HISTOPATHOLOGY : Partial architectural effacement Expanded paracortex with a

polymorphous proliferation of smaller and large lymphoid cells (immunoblasts) , histiocytes ,plasma cells and eosinophils - Mottled pattern

Immunoblasts may be morphologically atypical, sometimes resemble Reed-Sternberg cells, and form large aggregates

Increased mitotic activity Necrosis may be present

paracortex is expanded by sheets of immunoblasts.

Hematoxylin, phloxine, and saffron stain.

Special Stains and Immunohistochemistry Immunoblasts are CD20+ ,CD3+, CD 45 + CD30 + CD15 negative

EBV small-encoded RNA (EBER) probes are used most often for in situ hybridization analysis

Other Techniques for Diagnosis Paul-Bunnell test : MonoSpot test: Serology EBV viral load

DIFFERENTIAL DIAGNOSIS :1. DIFFUSE LARGE B-CELL LYMPHOMA : Occurs in older individuals neoplastic B-cell population is more

homogeneous with sheets of large transformed lymphocytes.

2. CLASSICAL HODGKIN LYMPHOMA : Reed-Sternberg cells express CD30 and CD15

CYTOMEGALOVIRUS LYMPHADENITIS

Caused by cytomegalovirus (CMV)

CLINICAL FEATURES : transmitted by blood transfusion , saliva ,respiratory secretions and transplacental passage fever, malaise, night sweats, enlarged lymph nodes, and mild hepatitis

HISTOPATHOLOGY : Architecture - effaced Diffuse paracortical immunoblastic hyperplasia Mottled histologic appearance Sheets of immunoblasts Hodgkin-like cells, Reed-Sternberg-like cells

cytoplasmic and nuclear staining with anti-CMV antibody

peroxidase stain.

HERPES SIMPLEX LYMPHADENITIS CLINICAL FEATURES - Lymphadenopathy

can be localized or generalized , painful and is rarely biopsied ,

HISTOPATHOLOGY :• architecture is distorted but preserved • Prominent paracortical hyperplasia with many immunoblasts

Multifocal necrosis with neutrophils, debris, and cells with viral inclusions

Cells with inclusions contain ground-glass nuclei or intranuclear eosinophilic inclusions with halos, chromatin margination, and multinucleation - COWDRY A

Special Stains and Immunohistochemistry :

Herpes simplex virus (HSV) immunostain is positive

Other Techniques for Diagnosis :• Viral culture • Serology

MEASLES Caused by Measles or history of recent vaccinationCLINICAL FEATURES : Axillary, cervical, inguinal lymph nodes

HISTOPATHOLOGY : Diffuse paracortical immunoblastic hyperplasia Mottled histologic appearanc Mild depletion of lymphocytes Proliferation of immunoblasts Warthin-Finkeldey giant cells

HIV LYPHADENOPATHY CLINICAL FEATURES : Acute symptomatic HIV infection-

characterized by fever, lymphadenopathy, sore throat, rash, myalgia/ arthralgia, and headache

The axillary, cervical, and occipital nodes are primarily enlarged

Persistent generalized lymphadenopathy is defined as lymphadenopathy of > 3-month duration involving at least two noncontiguous lymph node areas in the absence of other illness

HISTOPATHOLOGY : Pattern A (Acute): Hyperplastic, serpiginous

follicles folliculolysis Tingible-body macrophage Disruption of dendritic

network Mitoses Monocytoid aggregates Warthin-Finkeldey giant cell

Pattern B (Chronic) Effacement of follicles Involution of germinal

center Depletion of

lymphocyte Plasma cell Vascular hyperplasia

Pattern C (Burn-Out) : Small or absent follicles Hyalinized germinal

center Transfixing, collagen-

ensheathed arterioles (“lollipop” follicle)

Lymphocyte depletion Plasma cell Extensive angiogenesis

SPECIAL STAINS AND IMMUNOHISTOCHEMISTRY : core protein p24 gp41

OTHER TECHNIQUES FOR DIAGNOSIS : HIV serology HIV RNA detection (viral load) Flow cytometry for CD4 and CD8 T-cell subsets

DIFFERENTIAL DIAGNOSIS : 1. kaposi sarcoma Common in HIV patients Neoplastic proliferation of lymphatic endothelial cells with evidence of red blood cell extravasation and hyaline globules Extensive expression of HHV-8 by the endothelial cells

2. mycobacterium avium intracellulare infection Atypical mycobacterial infection in HIV patients may show a histiocytic proliferation with foamy or spindle histiocytes (mycobacterial pseudotumors) HIV-positive patients do not develop well-formed granulomas Acid-fast stain reveals numerous intracellular organisms

2.BACTERIAL LYMPHADENITIDES

CAT SCRATCH DISEASE :Caused by Bartonella henselae and transmitted by flea bites or cat bites and scratchesCLINICAL FEATURES : benign lymphadenopathy Occurs in immunocompetent children and

young adults Nodes (AXILLARY & CERVICAL ) are tender and

often have erythema of the overlying skin .

HISTOPATHOLOGY :1. Early lesions show follicular

hyperplasia, packing of sinuses by moncytoid B lymphocytes and histiocytic proliferation

2. Intermediate lesions – granulomatous changes

3. Late lesions – microabscesses with central necrosis and surrounded by histiocytes .

SPECIAL STAINS AND OTHER TESTS:

1. Warthin-Starry and Steiner stains identify the bacilli - Very small, pleomorphic, slender organisms ,Present singly, in clusters or chains

2. Serology (low sensitivity and specificity)

3. Blood or tissue culture 4. Tissue PCR (low sensitivity, but

high specificity)

DIFFERENTIAL DIAGNOSIS :

OTHER INFECTIOUS NECROTIZING LYMPHADENITIS - Chlamydia trachomatis (lymphogranuloma venereum), Francisella tularensis (tularemia), Hemophilus ducreyi (chancroid), and Yersinia enterocolitica (mesenteric lymphadenitis) may have identical histologic features - Clinical presentation is distinct - Gram stain, Giemsa stain, and Warthin-Starry

stain help identify the respective organisms.

BACILLARY ANGIOMATOSIS OF LYMPH NODES Tumor-like proliferations of small blood vessels

caused by Bartonella henselae. HISTOPATHOLOGY : 1. Vascular nodules replacing lymphoid tissue2. Admixed capillary and ectatic vessel3. Extravasated erythrocytes4. Interstitial eosinophilic granular material5. Clumps of Warthin-Starry–positive bacilli and

neutrophiles6. Endothelial cells with intracytoplasmic Weibel-

Palade bodies

LYMPHOGRANULOMA VENEREUM :

CLINICAL FEATURES : Caused by chlamydia trachomatis ( L1 ,L2,L3 ) Painless genital ulcers followed by lymphadenopathy

HISTOPATHOLOGY : -Tiny necrotic foci infiltrated by neutrophils -coalesce to form stellate abscess - Later stages – epithelioid cells ,langhans

giant cells , fibroblasts

Other tests : Frei test : delayed hypersensitivity skin test

Syphilis

caused by infection with Treponema pallidum

CLINICAL FEATURES : Nodes draining - inguinal, less commonly cervical, characteristically are enlarged but painless.

HISTOPATHOLOGY : Follicular hyperplasia Perivascular

lymphoplasmacytic infiltrate

Plasma cells in clusters and sheet

Epithelioid granuloma Isolated multinucleated

giant cell Capsular fibrosis

SPECIAL STAINS AND IHC :

Warthin-Starry stains demonstrate spirochetes,which are most numerous in and around small blood vessels.

Immunofluorescence PCR Southern Blotting

WHIPPLE DISEASECLINICAL FEATURES • Caused by Tropheryma whipplei, a gram-positive bacillus• Predilection for middle-aged white males • Typically presents with migratory arthralgias, followed by diarrhea, weight loss, and abdominal painUniform regional and frequent peripheral lymph node involvement

HISTOPATHOLOGY :

Dilation of the sinuses Foamy histiocytes Intracellular and extracellular PAS-

positive deposits of degenerated bacteria

Other Techniques for Diagnosis • Electron microscopy • PCR on tissue or fluid (saliva, stool) • Small intestinal biopsy is the gold standard for diagnosis

3.MYCOBACTERIAL LYMPHADENITIS

TUBERCULOSIS : Caused by mycobacterium tuberculae Clinical features : fever ,cough , most common

– cervical lymphadenopathy

FNAC : 1.multiple epithelioid cell granulomas 2. Multinucleated langhans type of gaint cells 3. caseous necrosis 4.reactive lymphoid cells.

Gross : large multinodular mass that resembles carcinoma with multiple foci of caseous necrosis ( white-yellow soft crumbly cheese-like)

HISTOPATHOLOGY : Multiple small epithelioid granulomas with Langerhans giant cells and central necrosis .

Special stains : AFB stain

Differential Diagnosis : 1.sarcoidosis - Granulomas are more uniform and compact

- Necrosis is rare, and when present it is focal - AFB stain is negative

2.Fungal lymphadenitis - Fungal forms can be identified on the H&E stained sections

- AFB stain is negative - Gomori methenamine silver (GMS) and

PAS stains highlight the fungal forms

3.foreign-Body type Granuloma - Granulomas are non-necrotizing

- foreign-body type giant cells

ATYPICAL MYCOBACTERIOSIS CLINICAL FEATURES :

M. avium complex (MAC), M. kansasii, M. scrofulaceum, M. malmoense, and M. haemophilum

occurs in immunocompetent children (1 to 5 years old) .

Presents as a unilateral, nontender node that slowly enlarges over several weeks .

GROSS : Enlarged and matted nodes

HISTOPATHOLOGY : granulomatous response is overshadowed by suppurative change ill formed and irregular granulomas

LEPROSY :

caused by Mycobacterium leprae.

CLINICAL FEATURES : Leprosy primarily involves skin and peripheral nerves; if left untreated it may spread to lymph nodes .

HISTOPATHOLOGY : progressive accumulation SHEETS of large , pale , rounded histiocytes ( lepra / Virchow cells ) with epithelioid granuloma formation with or no necrosis .

SPECIAL STAINS AND IHC : Wade – fite and fite faraco stains demonstrate packing of the cytoplasm by acid fast bacilli. Flourescent method PCR

4.FUNGAL LYMPHADENITIDES

CRYPTOCOCCUS LYMPHADENITIS

caused by Cryptococcus neoformans.

HISTOPATHOLOGY :1. Non-necrotizing granulomas2. Epithelioid cells and yeast-filled giant cells3. Cystic areas with gelatinous content

Mucicarmine stain.

HISTOPLASMA LYMPHADENITIS

caused by Histoplasma capsulatum.

HISTOPATHOLOGY :1. Epithelioid and giant cell granulomas2. Yeast-filled histiocytes and giant cells

Grocott methenamine silver stain.

5. PROTOZOAL LYMPHADENITIS

TOXOPLASMA LYMPHADENITIS

caused by Toxoplasma gondii

Clinical Features: - Immunocompetent persons, asymptomatic - lifelong risk of reactivation - bilateral, symmetrical, nontender cervical adenopathy

HISTOPATHOLOGY : Triad - reactive follicular hyperplasia with mitotic activity and phagocytosis of nuclear debris . - monocytoid B-cell hyperplasia - small granulomas composed entirely of epithelioid histiocytes within germinal centres . The histiocytes may be present as single cells or small clusters, typically encroaching on germinal centers The organism itself is identified in < 1% of cases • No evidence of significant necrosis

Special Stains and Immunohistochemistry : 1. sabin feldmen dye test 2. Ig M immunofluorescent antibody test 3. Toxoplasma immunostain is usually negative

due to absence of the parasites but occasionally may be useful .

4. Toxoplasma DNA identification by PCR in the tissue or blood

Differential Diagnosis :1. NoNspecific follicular Hyperplasia Does not have epithelioid histiocytes encroaching on germinal centers2. hiv lymphadenitis Does not have epithelioid histiocytes encroaching on germinal centers3. leishmaniasis Can have similar morphology Necrotizing or non-necrotizing granulomas with giant cells Intracellular organisms can be seen in the histiocytes with hematoxylin and eosin stain (H&E), Giemsa, and other special stains4. Lymphocyte predominant of hodgkins lymphoma

LEISHMANIA LYMPHADENITIS caused by Leishmania donovanii

HISTOPATHOLOGY : 1. Clusters of epithelioid cells and

granulomas2. Necrosis more common in

immunodeficient patients3. Amastigotes, round organisms that stain

strongly with hematoxylin

FILARIAL LYMPHADENITIS Wuchereria bancrofti

HISTOPATHOLOGY : 1. Necrotic center, microabscesses,2. Atrophic follicles, eosinophilia, granulomas

LYMPHADENOPATHIES

1. REACTIVE LYMPHADENOPATHIES

REACTIVE LYMPHOID HYPERPLASIA

ETIOLOGY : bacteria, viruses, chemicals, environmental pollutants, drugs, altered tissue components, and numerous other substances acting as antigens or allergens. Iatrogenic agents, medications such as phenytoin, allopurinol, atenolol, gold, penicillins, quinidine.

CLINICAL FEATURES :Fever, weight loss, pallor, and malaise

FNAC : 1. A mixed population of lymphoid cells 2. Centroblast ,centrocytes ,immunoblasts

, plasma cells , tingible body macrophages

HISTOPATHOLOGY : 1. Nonhomogeneous lymphocyte

population2. Reactive germinal center with

centroblasts, centrocytes, immunoblast ,plasma cells and tingible-body macrophages.

IHC :pan–B-cell monoclonal antibodies CD19, CD20, CD22, and CD79a

PROGRESSIVE TRANSFORMATION OF GERMINAL CENTERS

HISTOPATHOLOGY : 1. Partial replacement of

lymph node architecture by a nodule three to five times the diameter of surrounding reactive follicles.

2. germinal centers is infiltrated, to varying degrees, by mantle zone B cells.

2. LYMPHADENOPAHIES ASSOCIATED WITH CLINICAL

SYNDROMES

28 . KIMURA DISEASE CLINICAL FEATURES • presents as large painless subcutaneous masses and lymphadenopathy of the head or neck • East Asian males are classically affected • Up to 40% of the patients have salivary gland involvement • Patients have eosinophilia and elevated serum IgE level

FNAC : Polymorphous lymphoid population with significant eosinophils, fragments of collagenous tissue, endothelial cells and occasional polykaryocytes

HISTOPATHOLOGY : • Reactive follicular hyperplasia • Highly vascular germinal centers and paracortex • Germinal centers have deposition of eosinophilic proteinaceous material (IgE) • Germinal centers and paracortex contain numerous eosinophils with eosinophilic microabscesses and polykaryocytes • Prominent fibrosis may be seen

SPECIAL STAINS AND IMMUNOHISTOCHEMISTRY :

• IgE stains the dendritic meshwork of the germinal centers Other Techniques for Diagnosis• Laboratory workup reveals eosinophilia

ALHE

It does not look like lymphoid tissue in low magnification

Predominantly blood vessel disorder Dilated blood vessels with protuberant

endothelial cells Few or none lymphoid follicle Presence of smooth muscles in blood vessel wall Abundant mucin in blood vessel walls The number of eosinophils ranges from none to

many Subcutaneous tissue is not replaced by fibrosis It does not extend to muscle fascia

KIMURA

Similar to lymphoid tissue in low magnification

Predominantly lymphoid follicle disorder Absence of irregular and dilated blood vessels

Numerous lymphoid follicle

Absence of smooth muscles in blood vessel wall

Absent mucin in blood vessel walls There are numerous eosinophils Subcutaneous tissue is not highly replaced by fibrosis It extends to muscle fascia and sometimes to skeletal muscle

SINUS HISTIOCYTOSIS (ROSAI-DORFMAN DISEASE)

Also known as sinus histiocytosis with massive lymphadenopathy

Clinical Features :• Rare, self-limited histiocytic disorder of unknown etiology • Most common in children and young adults • Believed to be a reactive, polyclonal process • About 90% of patients present with bilateral cervical lymphadenopathy • Axillary, inguinal, and mediastinal lymph nodes also frequently involved • Patients also may have fever, weight loss, leukocytosis, anemia, elevated erythrocyte sedimentation rate (ESR

HISTOPATHOLOGY • Lymph node architecture is preserved • The capsule is thickened • There is marked dilation of the sinuses and numerous intrasinusoidal histiocytes • Very large cells with abundant eosinophilic cytoplasm and round nuclei with a single central nucleolus • A variable number of the histiocytes contain wellpreserved lymphocytes and, occasionally, plasma cells, neutrophils, and erythrocytes in their cytoplasm (emperipolesis) • The remaining intrasinusoidal infiltrate consists of small lymphocytes and abundant plasma cells

SPECIAL STAINS AND IMMUNOHISTOCHEMISTRY : • The histiocytes strongly express S-100 protein and other macrophage-associated antigens (CD14, CD68, CD163) • The histiocytes are negative for CD1a and langerin • Some cases have an increased number of IgG4-positive plasma cells

DIFFERENTIAL DIAGNOSIS :1. Nonspecific sinus histiocytosis • Lacks distinctive large histiocytes with round nuclei and prominent nucleoli • No evidence of emperipolesis • Histiocytes do not express S-1002. Langerhans cell histiocytosis • Langerhans cells are smaller and have irregular nuclei with grooves (coffee-bean shape) • Langerhans cells express CD1a and Langerin in addition to S-100 protein

NECROTIZING LYMPHADENITIS ( KIKUCHI’S LYMPHADENITIS ) :

CLINICAL FEATURES : japan Asian , young women , persistant painless cervical lymphadenopathy , accompanied by fever and leukopenia.

FNAC : abundant karyorrhectic debris and histiocytes

absence of plasma cells and neutrophils histiocytes have phagocytosed material in the cytoplasm and eccentric nuclei ( plasmacytoid monocyte like appearance ) .

HISTOPATHOLOGY : Nodes show partially effaced architecture with large, discrete areas of eosinophilic necrosis with abundant karyorrhectic debris surrounded by transformed lymphocytes, histiocytes, and plasmacytoid monocytes.

* plasma cells and neutrophils are scanty – diagnostic importance *

*The origin of Kikuchi-Fujimoto disease is unknown. Although viruses such as human herpesvirus 6, EBV, and hepatitis B have been linked to Kikuchi-Fujimoto disease, these associations have not been confirmed*

IHC : CD8 positivity for – lymphocytes , CD68 positivity for histiocytic cells , Plasmacytoid dendritic cells are positive for CD123.

Differential diagnosis : Necrotizing granulomatous lymphadenitis : Well-formed necrotizing granulomas with many

multinucleated giant cells ,Epithelioid histiocytes are seen Cresecent shaped nuclei in histiocytes – kikuchi AFB stain reveals mycobacteria.

SARCOIDOSISCLINICAL FEATURE : Multisystem granulomatous disease of unknown cause characterized by bilateral hilar adenopathy, pulmonary infiltrates, Peripheral lymphadenopathyand ocular and skin lesions. Young black women are often affected. FNAC :

Clusters of loosely cohesive epithelioid histiocytes with characteristically pale, elongated sole-shaped nuclei

few lymphocytes no necrosis and giant cells seen

Other investigations :

Kveim test : Intradermal inoculation of extract from human spleen (diseased)

biopsy taken after 4 to 6 weeks later

Positive – sarcoid type granulomas

HISTOPATHOLOGY : - Multiple compact well-defined granulomas - Granulomas are composed of epithelioid histiocytes and multinucleated giant cells - Necrosis is typically absent .- Schaumann bodies are round , have

concentric laminations contains iron and calcium .

- Astroid bodies are radiating filamentous arms enveloped by myelonoid membranes .

Special stains : PAS Positive inclusions – hamazaki wesenberg bodies ( yellow and ovoid )

IHC : Ki 67 and interleukin -1

LUPUS ERYTHEMATOSUS : CLINICAL FEATURES : Chronic inflammatory disease of unknown cause affect the skin, joints, kidneys, lungs, nervous system, serous membranes, and many other organs Enlargement of lymph nodes occurs in approximately 50% of patients Lymph nodes are soft, nontender, and discrete cervical, axillary, and inguinal areas

LABORATORY TESTS : neutropenia, anemia, and positive tests for antinuclear antibodies (double-stranded DNA and Smith antigen)

HISTOPATHOLOGY :• Edema, hemorrhage, and areas of necrosis surrounded by histiocytes and immunoblasts • Some cases contain abundant plasma cells • Hematoxylin bodies (ill-defined purple structures in necrotic foci) are typical of lupus • Azzopardi phenomenon (dark blue DNA material deposited on the basement membrane of blood vessels) is typical of lupus • Prominent follicular hyperplasia and capsular inflammation may be present.

SPECIAL STAINS AND IMMUNOHISTOCHEMISTRY :

• CD8+ cytotoxic T lymphocytes are prominent • Histiocytes express lysozyme, CD68, and myeloper oxidase • Plasmacytoid dendritic cells are positive for CD123

RHEUMATOID ARTHRITIS : CLINICAL FEATURES : Generalized adenopathy ,weight loss, anemia, and fever.

HISTOPATHOLOGY : architectural preservation large hyperplastic follicles in both the cortex and medulla, surrounded by impressive aggregates of interfollicular plasma cells and tingeble body macrophages. Russell bodies may be prominent.

DERMATOPATHIC LYMPHADENITIS Clinical Features : • Found in patients with benign and malignant chronic skin conditions • occurs in the lymph nodes that drain the affected area • Axillary and inguinal lymph nodes are most commonly affected Histopathology : • lymph node architecture is preserved • Marked diffuse or nodular expansion of the paracortex • Proliferation of interdigitating dendritic cells, Langerhans cells, and histiocytes that contain melanin pigment

SPECIAL STAINS AND IMMUNOHISTOCHEMISTRY :• CD4+ T cells • Langerhans cells express S-100 and CD1a • Histiocytes are highlighted by CD68 and CD163

Other Techniques for Diagnosis • T-cell receptor gamma gene (TCR) rearrangement shows polyclonal T lymphocytes

CASTLEMAN’S DISEASE : CLINICAL FEATURES - Atypical lymphoproliferative disease divided into three

subtypes: 1.unicentric hyaline-vascular type 2. unicentric plasma cell type 3. multicentric

• Unicentric hyaline-vascular type – most common subtype , benign lymphoproliferative disorder of young adults ,Majority occurs in mediastinum • Unassociated with HHV-8 infection • Curable with surgical resection .

• Unicentric plasma cell type - Similar presentation to unicentric hyaline-vascular type systemic findings: anemia, elevated sedimentation rate, hypergammaglobulinemia,

and bone marrow plasmacytosis •

Multicentric - Middle-aged and elderly adults , generalized peripheral lymphadenopathy, hepatosplenomegaly, frequent fevers, and night sweats , Strongly associated with immunosuppression (e.g., HIV) and HHV-8 infection

associated malignancy (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes [POEMS] syndrome, Kaposi sarcoma, Hodgkin and non-Hodgkin lymphoma

HISTOPATHOLOGY :

• HYALINE-VASCULAR TYPE – Abnormal follicles with atrophic or “regressed” hyalinized germinal centers, which contain numerous follicular dendritic cells - The follicles are surrounded by broad mantle zones of small lymphocytes, present in an “onion skin” arrangement - Two or more adjacent germinal centers may be surrounded by a single mantle zone - The regressed germinal centers are often radially penetrated by a hyalinized blood vessel (“lollipop follicle”)

Plasma cell type • A mixture of hyperplastic germinal centers and regressed follicles • The interfollicular region is hypervascular and contains sheets of plasma cells

Plasmablastic type - atypical-appearing large cells with plasmablastic morphology (previously called “microlymphoma”) - Present inside germinal centers and in interfollicular areas

Special Stains and Immunohistochemistry : CD21-positive, CD23-positive follicular dendritic cell meshworks • Plasma cell variant may contain monotypic plasma cells, usually of IgGλ or IgAλ isotype (up to half of the cases) • Plasmablastic type contains IgMλ−restricted atypical large cells

Other Techniques for Diagnosis :• Elevated serum levels of Il-6 • Tissue PCR for HHV-8 • IgH gene rearrangement shows no evidence of B-cell clonality

SJÖGREN SYNDROME

HISTOPATHOLOGY :

progressive atrophy and replacement of salivary acini and ducts by abundant lymphoid tissue

3.IATROGENIC LYMPHADENOPATHIES

DRUG INDUCED : CLINICAL FEATURE : either mephenytoin (Mesantoin) or phenytoin (Dilantin) 1 to 6 weeks before experiencing tender bilateral cervical lymphadenopathy accompanied by fever, eosinophilia, and a variety of skin changes, ranging from morbilliform rashes to exfoliative dermatitis.

HISTOPATHOLOGY : early lesions were characterized by PARTIAL EFFACEMENT. histiocytes , immunoblasts, plasma cells, and eosinophils with varying degrees of vascular proliferation are seen .

SPECIAL STAINS AND IMMUNOHISTOCHEMISTRY - Immunoblasts express CD30 and are negative for CD15 .

4.VASCULAR LYMPHADENOPATHIES

LYMPH NODE INFARCTION result from infection, vasculitis, or trauma Lymphomas associated with lymph node infarction are typically diffuse

large-B-cell lymphomas, but they also include follicular lymphoma, T-cell lymphomas, and HL.

HISTOPATHOLOGY : Massive ischemic necrosis Peripheral rim of spared lymphoid tissue Ghostlike necrotic lymphocytes or lymphoma cells Preservation of reticulin network Thrombosis of hilar or intranodal vessels

VASCULAR TRANSFORMATION OF LYMPH NODE SINUSES

Vascular transformation of lymph node sinuses is usually found incidentally after resection of a nearby tumor.

HISTOPATHOLOGY : 1. Vascular proliferation within lymph node sinuses2. Association with vascular obstruction3. Cleft-like, rounded, solid, and plexiform patterns4. Erythrocyte extravasation5. Fibrosis

5. FOREIGN BODY LYMPHADENOPATHY

1. PROTEINOUS LYMPHADENOPATHY :

FOREIGN BODY LYMPHADENOPATHY

periodic acid–Schiff-positive proteinaceous material

2. SILICONE LYMPHADENOPATHY :

Histiocytes with fine strands of refractable material probably polyurethane surrounded by foreign-body giant cells.

Miscellaneous

1. MESENTRIC ( masshoff’s ) LYMPHADENITIS : CLINICAL FEATURES : Yersinia pseudotuberculosis / Yersinia

enterolitica benign , self limited HISTOPATHOLOGY : capsular thickening , edema ,increase in immunoblast and plasma cells in the cortical and paracortical regions small granulomas and abscesses OTHER INVESTIGATIONS : Culture – confirmative PCR

2. BRUCELLOSIS :

Caused by Brucella abortus ,melitensis or suis CLINICAL FEATURES : Occupational to a foodborne illness ( milk

and cheese ) fever , lymphadenopathy ,spelenomegaly HISTOPATHOLOGY :Non specific follicular hyperplasia , clusters of epithelioid histiocytes , rarely non caseating granulomas , plasma cells ,eosinophils , immunoblasts are evident .

Definitive diagnosis – PCR

3. MUCOCUTANEOUS LYMPH NODE SYNDROME

Also known as Kawasaki’s syndrome

CLINICAL FEATURES : febrile illness affecting children fever , cervical lymphadenopathy ,pharyngeal and conjunctival inflammation , erythematous skin rashes .

HISTOPATHOLOGY : Affected node shows fibrin thrombi in small vessels

4.ANGIOLYMPHOBLASTIC LYMPHADENOPATHY :

CLINICAL FEATURES : Adults , Fever , anaemia , polyclonal hypergammaglobulinemia and generalised lymphadenopathy

HISTO PATHOLOGY : - obliteration of nodal architecture by a polymorphic cellular infiltrate ( small lymphocytes , plasma cells , immunoblasts , eosinophils ) and by an extensive proliferation of finely arborizing vessels - “ BURNT- OUT GERMINAL CENTRES “

SPECIAL STAINS : 1. METHYL GREEN PYRONINE STAIN – large lymphoid cells are

pyroninophilic 2. IMMUNOPEROXIDASE STAIN – polyclonal pattern of

immunoglobulin production .

REFERENCES :

1. Ioachim’ s lymph node pathology ,4th edition 2.Mills SE , Carter D ,Sternberg diagnostic pathology , 4th

edition , Lipincott Williams and wilkins. 3.Rosai J,Rosai and Ackerman surgical pathology, 9th

edition . 4. Orell & sterrett’s fine needle aspiration cytology, 5th

edition 5. Differential diagnosis in surgicalpathology ,3rd edition 6.Internet sources

EXTRA NOTES

Post-Transplant Lymphoproliferative Disorder

life-threatening complication of both solid organ and bone marrow transplantation.

incidence ranges from 1% to 10% and is influenced by the type of transplant and the particular immunosuppressive protocol.

linked to EBV infection by serologic tests and molecular studies of involved tissues.

PTLD often occurs at extranodal sites (central nervous system, lung, small bowel) and may involve the allograft in a histologic pattern mimicking rejection.

Plasmacytic hyperplasia (PH) or infectious mononucleosis-like PTLD characteristically occurs early in the posttransplant period, is more common in children and young adults, and frequently involves lymph nodes and tonsillar tissue.

Plasma cell hyperplasia may be admixed with a few immunoblasts that do not show cytologic atypia. Both plasma cell hyperplasia and the infectious mononucleosis-like lesions demonstrate architectural preservation.

These lesions are genetically and immunophenotypically polyclonal, with EBV-latent membrane protein demonstrable by IHC.

Polymorphic PTLD is more clinically aggressive and is characterized by architectural effacement by a mixed population of immunoblasts, plasma cells, and lymphocytes, pleomorphic in size and cytology.

There may be necrosis and significant cytologic atypia. EBV-associated antigens are usually detected by IHC . Monomorphic PTLD meets morphologic criteria for malignant

lymphoma, most commonly diffuse large-B-cell lymphoma, with Burkitt lymphoma, plasmacytic neoplasms, and T-cell lymphomas constituting most of the remaining cases.

Prognosis is related to stage, performance status site, histologic features, EBV status and clonality as defined by flow cytometry.

Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, cytopenia, hepatosplenomegaly, abnormal liver function tests, hypertriglyceridemia, and hypofibrinogenemia.

Erythrophagocytosis must be present in bone marrow, lymph nodes, or spleen .

Patients with HLH have high levels of circulating cytokines, including interferon gamma, interleukin-2, and TNF-α, that may contribute to macrophage activation

Lymph node biopsy reveals intact architecture, with infiltration of cortex, sinuses, and paracortex by histiocytes that are cytologically benign and filled with erythrocytes . The interfollicular areas may show vascular proliferation, more numerous plasma cells, and immunoblasts. Follicular centers may be atrophic or depleted.

It is important to recognize that hemophagocytosis in tissue sections without the clinical features of HLH is a common finding in a variety of circumstances, including posttransfusion

HPS is usually distinguishable from malignant histiocytosis by its clinical context, benign histiocyte cytologic features, and architectural preservation.

Vasoproliferative and Spindle Cell Lesions of Lymph Node, including Kaposi Sarcoma

Several benign lesions in lymph nodes are dominated by proliferation of spindle cells and vascular channels.

Many of these lesions are seen in immunosuppressed patients.

In HIV-infected patients, KS is typically lymphadenopathic or extracutaneous. It frequently involves capsular and subcapsular regions of lymph node, forming nodular masses that extend into and efface the underlying parenchyma.

Usually, small vessels with plump and atypical endothelial cells alternate with areas of spindle cell proliferation containing slitlike spaces with extravasated erythrocytes and hemosiderin.

The tumor often contains plasma cells. Mitotic figures are common

The remaining lymph node may show typical features of HIV-associated adenopathy .

PCR confirms the presence of HHV8 DNA in more than 95% of cases

Inflammatory Pseudotumor of Lymph Nodes

Patients are commonly young adults with localized adenopathy accompanied by fever and other signs of systemic inflammatory disease.

Lesions involve the connective tissue framework of the node (capsule, sinuses, hilum) and are composed of small blood vessels, fibroblasts, and inflammatory cells, including plasma cells, neutrophils, eosinophils, and macrophages.

Intranodal areas of fibroblastic proliferation are prominent; extension into perinodal soft tissues with accompanying obliterative vasculitis is common .

Many of the spindle cells show a phenotype suggestive of a macrophage (CD45+, CD68+, HDA-DR+)

Inflammatory pseudotumor is distinguished from KS by the absence of dense spindle cell proliferation in the parenchymal portions of the node; extravasated erythrocytes and slitlike vascular spaces are also usually not present.

Lymphomas with prominent vascularity are excluded by the absence of cytologic atypia and monomorphism.

Mycobacterial Spindle Cell Pseudotumor

Mycobacterial spindle cell pseudotumor is almost always seen in patients with HIV infection and involve many sites- skin, spleen, and lymph nodes.

In lymph nodes, there is partial or complete alteration of nodal architecture by a proliferation of cytologically bland spindle cells, often producing a storiform pattern.

The spindle cells mark as macrophages with CD45, CD68, and HDA-DR. Numerous acid-fast bacilli are evident on Ziehl-Neelsen stain.

The startling ability of this proliferative lesion to mimic neoplastic spindle cell tumors suggests that acid-fast stains should be a part of the evaluation of any spindle cell lesion lacking nuclear atypia in immunodeficient patients

Palisaded Myofibroblastoma (Intranodal Hemorrhagic Spindle Cell Tumor with Amianthoid Fibers)

Palisaded myofibroblastoma arises almost exclusively in lymph nodes in the groin

composed of interlacing fascicles of spindle cells that surround large mats of eosinophilic material (amianthoid fibers).

These tumors may be highly vascularized, with associated hemorrhagic foci, and compress adjacent node parenchyma.

Spindle cells show focal nuclear palisading mimicking neurilemoma.