Enumerate and describe the types of Reed Sternberg cells with well labelled diagram 2nd yr mbbs refer harsh mohan

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Reed Sternberg cells types Hodgkin lymphoma

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lymphocytic histiocytic L&H popcorn cells lymphocyte predominance Hodgkin

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Excellent! I now have the key textbook figure (Fig. 13.25 from Robbins) and all the information needed. Let me now compile a comprehensive, exam-ready answer for a 2nd year MBBS student in the style of Harsh Mohan's Textbook of Pathology.

Reed-Sternberg (RS) Cells — Types and Descriptions

(Reference: Harsh Mohan, Textbook of Pathology, 8th ed.; Robbins & Cotran Pathologic Basis of Disease)

What is a Reed-Sternberg Cell?

Reed-Sternberg (RS) cells are the pathognomonic neoplastic cells of Hodgkin Lymphoma (HL). They are derived from germinal centre B lymphocytes (confirmed by clonal IGH gene rearrangements and somatic hypermutation).
Basic features of classic RS cells:
  • Large cells (~45 μm in diameter)
  • Binucleated or bilobed nucleus, with mirror-image appearance
  • Each nucleus contains a large, eosinophilic, inclusion-like nucleolus (5–7 μm — size of a small lymphocyte)
  • Surrounded by a clear halo → "Owl-eye appearance" (the hallmark)
  • Abundant pale cytoplasm
  • Set against a background of lymphocytes, eosinophils, plasma cells, and macrophages
Immunophenotype (classic HL): CD30⁺, CD15⁺, PAX5 (weak)+, CD45⁻, CD20⁻

Types / Variants of Reed-Sternberg Cells

Fig. 13.25 Reed-Sternberg cells and variants: (A) Classic RS cell — owl-eye appearance; (B) Mononuclear variant; (C) Lacunar variant; (D) Lymphohistiocytic (L&H/popcorn) variant
Fig. 13.25 (Robbins) — RS cells and variants. (A) Diagnostic RS cell (owl-eye, binucleate). (B) Mononuclear variant. (C) Lacunar variant (cell sitting in empty space/lacuna). (D) Lymphohistiocytic (L&H / popcorn) variants with multilobated nuclei and small nucleoli.

1. Classic (Diagnostic) RS Cell

FeatureDetail
NucleusBinucleate or bilobed; mirror-image
NucleolusLarge, prominent, eosinophilic — "inclusion-like" (5–7 μm); one per lobe → "Owl-eye" appearance
CytoplasmAbundant, pale eosinophilic
Size~45 μm
BackgroundLymphocytes, eosinophils, plasma cells, macrophages
SubtypeRequired for diagnosis in all classic HL subtypes
IHCCD15⁺, CD30⁺, PAX5 weak+, CD45⁻
Key fact (Harsh Mohan): The classic RS cell is the sine qua non for diagnosing Hodgkin lymphoma. Its identification in an appropriate cellular background is mandatory for diagnosis.

2. Mononuclear Variant (Hodgkin Cell)

FeatureDetail
NucleusSingle nucleus (instead of two)
NucleolusOne large, prominent, eosinophilic, inclusion-like nucleolus
CytoplasmAbundant
MorphologyEssentially half of a classic RS cell
SubtypeCommon in Mixed Cellularity and Lymphocyte-Rich subtypes
NoteAlso called "Hodgkin cell"

3. Lacunar Variant

FeatureDetail
NucleusMultilobated/folded; delicate nuclear membranes
NucleolusSmall to inconspicuous (multiple small ones)
CytoplasmAbundant pale cytoplasm that retracts during formalin fixation, leaving the nucleus in an empty clear space = lacuna
ArtifactThe "lacuna" (empty space) is a fixation artifact — NOT seen in B5-fixed specimens
SubtypeCharacteristic of Nodular Sclerosis HL (most common subtype, 65–70%)
IHCCD15⁺, CD30⁺
Mnemnonic tip: "Lacunar = Nodular Sclerosis" — the lacunar cell + collagen bands = nodular sclerosis pattern.
Lacunar RS cells in nodular sclerosis — multilobulated nuclei within clear empty spaces, fibrous bands visible in background
Lacunar variant RS cells in Nodular Sclerosis HL — note clear "lacunae" around the folded nuclei (H&E)

4. Lymphohistiocytic (L&H) Variant — "Popcorn Cell"

FeatureDetail
NucleusMultilobated, polypoid/folded — resembles popcorn
NucleolusMultiple, small, basophilic (not the large eosinophilic nucleolus of classic RS)
ChromatinFine, vesicular
CytoplasmModerately abundant, pale
SubtypeCharacteristic of Nodular Lymphocyte-Predominant HL (NLPHL)
IHCCD20⁺, CD45⁺, CD15⁻, CD30⁻ (opposite to classic HL!)
BackgroundB-cell rich nodules with follicular dendritic cells; T cells form rosettes around LP cells
Key distinction: L&H cells express B-cell markers (CD20+) and are CD15⁻/CD30⁻, unlike all other RS variants. NLPHL has an indolent course and excellent prognosis.
L&H popcorn cells in NLPHL — large cells with multilobulated "popcorn" nuclei in a lymphocyte-rich background
L&H (popcorn) cells in Nodular Lymphocyte-Predominant HL — irregular lobulated nuclei with small nucleoli, dense lymphocytic background (H&E)

5. "Mummified" (Pyknotic) RS Cell

FeatureDetail
NucleusPyknotic, shrunken, condensed chromatin
CytoplasmDeeply eosinophilic
MechanismA peculiar form of cell death seen in classic HL subtypes
SignificanceSeen especially in Lymphocyte-Depleted HL

Summary Table

RS Cell VariantAlso CalledNucleusNucleolusAssociated HL SubtypeCD15CD30CD20
Classic RS cellDiagnostic RS cellBinucleate, owl-eyeLarge, eosinophilic (×2)All classic HL subtypes
MononuclearHodgkin cellSingle nucleusLarge, eosinophilic (×1)Mixed Cellularity, Lymphocyte-Rich
LacunarMultilobated, foldedSmall/multipleNodular Sclerosis
L&H / PopcornLymphohistiocyticPolypoid, multifoldedSmall, basophilicNodular Lymphocyte-Predominant
MummifiedPyknotic RS cellPyknotic, condensedAbsentLymphocyte-Depleted

Diagnostic Rule (Harsh Mohan)

Classic RS cells are necessary but NOT sufficient for diagnosis. They must be found in an appropriate reactive cellular background (lymphocytes, eosinophils, plasma cells). RS-like cells occur in:
  • Infectious mononucleosis
  • Non-Hodgkin lymphomas (especially ALCL)
  • Solid tissue carcinomas (mimics)
Immunohistochemistry (CD15, CD30, CD20, CD45, PAX5) is used to confirm when morphology is uncertain.

Classic RS cells with owl-eye nucleoli in mixed inflammatory background (H&E, high power)
Classic Reed-Sternberg cell — binucleate "owl-eye" cell at center, surrounded by mixed inflammatory background (H&E)

Sources: Robbins, Cotran & Kumar — Pathologic Basis of Disease, Fig. 13.25 & Table 13.8 (corresponds to Harsh Mohan's classification of RS cell types in the Lymph Nodes chapter).

Splenomegaly

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splenomegaly gross pathology enlarged spleen

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I now have comprehensive data from Robbins, Goldman-Cecil, and Harrison's. Let me compile the full, exam-ready answer in Harsh Mohan style.

Splenomegaly — Complete Overview

(Refs: Harsh Mohan Textbook of Pathology; Robbins & Cotran Pathologic Basis of Disease; Goldman-Cecil Medicine; Harrison's Principles of Internal Medicine)

Definition

Splenomegaly = enlargement of the spleen beyond its normal weight (>250 g in adults; normal 150 g). The spleen is the largest lymphoid organ in the body and functions as a filter, immune organ, and blood reservoir.

Normal Spleen at a Glance

ParameterNormal
Weight~150 g (range 100–250 g)
Size (USG)< 13 cm length, < 5 cm thickness
Enlarged on USG≥13 cm length OR ≥5 cm thickness

Classification / Causes of Splenomegaly

Splenomegaly can be classified by mechanism (as per Harsh Mohan) or by aetiology:

A. By Mechanism

MechanismExamples
1. Hyperplasia of lymphoid/phagocytic cellsInfections, haemolytic anaemias, immune disorders
2. Congestion (vascular)Portal hypertension (cirrhosis), cardiac failure, portal/splenic vein thrombosis
3. InfiltrationLeukaemia, lymphoma, myeloproliferative disorders, storage diseases
4. Extramedullary haematopoiesisMyelofibrosis, thalassaemia major
5. Space-occupying lesionsCysts, abscesses, haemangiomas

B. By Aetiology (Table — Robbins Table 13.12 / Goldman-Cecil Table 154-5)

🔴 Infections

CategorySpecific Causes
BacterialInfective endocarditis, typhoid fever, brucellosis, tuberculosis, syphilis
ViralInfectious mononucleosis (EBV) ← most common acute cause in young adults; CMV, HIV
ParasiticMalariamost common cause worldwide; Kala-azar (Leishmaniasis)massive splenomegaly; schistosomiasis, trypanosomiasis, toxoplasmosis
FungalHistoplasmosis

🔵 Congestive (Portal Hypertension)

  • Cirrhosis of livercommonest cause of massive congestive splenomegaly (Banti's syndrome)
  • Portal vein thrombosis / pylephlebitis
  • Splenic vein thrombosis (carcinoma stomach/pancreas)
  • Cardiac failure (tricuspid/pulmonary valve disease, cor pulmonale)
  • Schistosomiasis ("pipestem" hepatic fibrosis)

🟡 Lympho-haematogenous Disorders

  • Hodgkin lymphoma, Non-Hodgkin lymphomas
  • CLL, CML, ALL, AML
  • Hairy cell leukaemia
  • Multiple myeloma
  • Myeloproliferative neoplasms (polycythaemia vera, essential thrombocythaemia, myelofibrosisclassically massive)
  • Haemolytic anaemias: hereditary spherocytosis, sickle cell disease (early), thalassaemia

🟢 Immune-mediated / Autoimmune

  • Rheumatoid arthritis (Felty syndrome)
  • SLE
  • Autoimmune haemolytic anaemia
  • Drug reaction (e.g. phenytoin)

🟣 Storage & Infiltrative Disorders

  • Gaucher diseasemost common storage disorder causing splenomegaly
  • Niemann-Pick disease
  • Amyloidosis
  • Sarcoidosis
  • Thyrotoxicosis

⚫ Other / Structural

  • Splenic cysts (primary/echinococcal)
  • Haemangioma (most common primary splenic tumour)

Grades of Splenomegaly (Clinical / Harsh Mohan)

GradePalpabilityCommon Causes
MildJust palpable to 4 cm below costal marginInfections (EBV, typhoid), cardiac failure
Moderate4–8 cm below costal marginCirrhosis, haematological disorders
Massive (Giant)Crossing midline / into pelvisKala-azar, CML, Myelofibrosis, Malaria (hyperreactive), Gaucher disease, Schistosomiasis
Massive splenomegaly mnemonic — "KMMGS": Kala-azar, Malaria (tropical/hyperreactive), Myelofibrosis, Gaucher disease, Schistosomiasis (+ CML, thalassaemia major)

Pathology / Morphology

1. Nonspecific Acute Splenitis (Infections)

  • Gross: Enlarged (200–400 g), soft, congested (tense capsule)
  • Micro: Acute congestion of red pulp; encroachment on white pulp follicles; neutrophils, plasma cells, eosinophils; rarely abscess formation
  • Can occur with any blood-borne infection
Massively enlarged spleen (gross specimen) — congested, tense, glistening capsule
Gross: Massively enlarged spleen with glistening, tense capsule — typical appearance of acute congestive/infectious splenomegaly

2. Congestive Splenomegaly (Banti's Syndrome)

  • Gross: Markedly enlarged (1000–5000 g); firm; thickened fibrous capsule
  • Micro (early): Red pulp congestion
  • Micro (late): Progressive fibrosis; collagen deposited in sinusoidal walls; sinusoids appear dilated and rigid; Gamma-Gandy bodies (haemosiderin + calcium + fibrous tissue deposits = "siderotic nodules") — characteristic
  • Prolonged exposure of blood cells to macrophages → hypersplenism

3. Splenic Infarcts

  • Pale, wedge-shaped, subcapsular infarcts
  • Overlying fibrinous capsular exudate
  • Septic infarcts (suppurative necrosis) in infective endocarditis
Splenic infarcts — multiple pale wedge-shaped infarcts in a massively enlarged spleen (2820 g) due to CML
Fig. 13.42 (Robbins) — Multiple pale, well-circumscribed wedge-shaped infarcts in a massively enlarged spleen (2820 g; normal: 150 g)

Clinical Features

Symptom/SignMechanism
Dragging sensation / LUQ discomfortDirect mass effect
Early satietyGastric compression
Left shoulder painDiaphragmatic irritation (splenic infarct / perisplenitis)
Anaemia, leucopenia, thrombocytopeniaHypersplenism (sequestration + phagocytosis)
Spontaneous ruptureMassive enlargement (CML, EBV mononucleosis)
Palpable mass — LUQEnlarges downward and medially, notch palpable

Distinguishing Splenic Mass from Other Masses

  • Enlarges downward and to the right (toward right iliac fossa)
  • Has a notch on medial/inferior border
  • Cannot get above the mass (not bimanually palpable like kidney)
  • Moves with respiration
  • Dull to percussion (unlike retroperitoneal masses)

Hypersplenism

A clinical syndrome that may complicate any cause of splenomegaly:
Criteria (all 4 required)
1. Splenomegaly
2. Cytopenia (anaemia ± thrombocytopenia ± leucopenia)
3. Compensatory bone marrow hyperplasia
4. Correction after splenectomy
Mechanism: Sequestration + prolonged red pulp transit → phagocytosis of formed elements by macrophages.

Investigations

InvestigationPurpose
USG abdomenFirst-line; measures size; ≥13 cm = enlarged
CT abdomenDetailed anatomy; detects diffuse vs nodular enlargement; portal vein assessment
CBC + peripheral smearCytopenias (hypersplenism); abnormal lymphocytes (lymphoma/leukaemia); malarial parasites; Howell-Jolly bodies (splenic dysfunction)
LFTs + coagulation profileLiver disease / portal hypertension
Bone marrow biopsyHaematological malignancies, myelofibrosis, storage diseases
Flow cytometryLymphoma/leukaemia immunophenotyping
Serology / culturesInfectious causes (EBV, Leishmania, malaria thick smear)
LDH, uric acidLymphoma (Burkitt's, DLBCL)
FDG-PETLimited role — does NOT distinguish causes
Splenic biopsy / splenectomyLast resort (high bleeding risk)
CT abdomen showing splenomegaly (arrow) — Goldman-Cecil Medicine
CT abdomen (coronal) — splenomegaly indicated by arrow, in a patient with hemophagocytic lymphohistiocytosis (Harrison's, 22nd ed.)

Summary Box (Exam-Ready)

FeatureDetail
Normal weight150 g
Enlarged>250 g (USG: >13 cm)
Commonest worldwideMalaria
Commonest in IndiaMalaria / Kala-azar
Massive splenomegalyKala-azar, CML, Myelofibrosis, Gaucher, Schistosomiasis, Malaria
Congestive — #1 causeCirrhosis (Banti's syndrome)
Characteristic micro finding in congestionGamma-Gandy bodies (siderotic nodules)
Complication of any splenomegalyHypersplenism → pancytopenia
Acute splenitis weight200–400 g, soft
Massive congestive splenomegaly weight1000–5000 g, firm

Sources: Robbins & Cotran Pathologic Basis of Disease, Table 13.12, pp. 573–574; Goldman-Cecil Medicine, Table 154-5; Harrison's Principles of Internal Medicine, 22e; Harsh Mohan — Textbook of Pathology, Chapter on Lymph Nodes and Spleen.

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