My PG

MEE
Notes

Plasma Cell Tumors 

Multiple Myeloma
zz Plasma cell markers→CD138 (Syndecan)
zz Features:
 monoclonal plasma cells →M component→ IgG (most common) →cannot be excreted in urine
 extra light chains Bence Jones protein→ excreted in urine
Il-6 (osteoclast activating factor)→ producers lytic bone lesions and hypercalcemia bones

Medicine

(MC- vertebra), patient will have bone pains and pathological fractures
 PS→ normocytic normochromic anaemia with rouleaux formation
zz BM aspiration:
 > 10% monoclonal plasma cells
 plasmablast binucleate plasma cells
Russell bodies(Cytoplasm) and ditcher(Nucleus) bodies

/e


 flame cells → plasma cells with Fiery red cytoplasm

,1
zz ↑ calcium → kidney involved→ Renal failure→↑ Creatinine
zz AL type Amyloidosis can be seen.

es
zz Most important prognostic marker →ß microglobulin
zz repeated infections ( most common cause of death in MM)
ot
zz criteria for diagnosis:
M protein in serum or urine
N


 IgG > 30 gram per / litre

Bence Jones protein courier > 1gm/24 hour
EE



 monoclonal plasma cells in bone marrow > 10%

 related organ or tissue insufficiency [ROTI]
Figure:  Mott cells in Multiple Myeloma [2018]
CRAB –hyperCalcemia, Renal insufficiency, Anaemia,
M


lytic Bone lesions
PG

zz Smoldering myeloma→ a variant in which lab criteria is met but the patient is asymptomatic
no ROTI
zz Treatment:
Autologous stem cell therapy
y



Lenalidomide + Dexamethasone+ bortezomib

M



 Carfilzomib (in aggressive cases)

Monoclonal Gammapathy Of Waldenstrom’s macroglobulinemia /

Undetermined Origin [MGUS] Lymphoplasmacytic Lymphoma
• Bone marrow clonal plasma cells < 10% zz monoclonal antibody IGM class→produces hyperviscosity
• M protein in serum < 30 gm/L
syndrome → sluggish blood flow →ischemia to brain and
• Bence-Jones protein < 1 gm/24 hour
retina (unconsciousness and blurring of vision)
• No OAF release
• No Lytic lesions zz can precipitate at cold temperature producing Cold
• no ROTI AIHA
zz Hepatomegaly and splenomegaly present
zz bleeding tendencies due to IGM antibody-coagulation 345
factor complexes.

notes
 MEE
My PG
Notes

PERIPHERAL T CELL TUMORS

Adult T cell Mycosis fungoides / Anaplastic large cell Extranodal NK Large
leukaemia / sezary syndrome lymphoma / T cell tumor granular cell
lymphoma lymphoma
• arises from • also known as cu- • arises from CD3+ T cells • Also called as • arises from
CD4+ T cells taneous T-cell lym- • CD3and CD30 positive ANGIOCEN- CD8 T cell
• HTLV1 Asso- phoma. • epithelial membrane anti- TRIC LYM- • associated
ciation • tumor of CD4+ gen positive PHOMA / LE- with felty’s
• associated Tcells • tumor cells with large THAL MIDLINE syndrome
Medicine

with skin le- • PAS positive HORSESHOE SHAPED NU- GRANULOMA [RA + sple-
sions, Lym- • cutaneous lym- CLEUS →HALLMARK CELLS • arises from NK nomegaly +
phadenopathy, phoma [epidermi- OR DOUGHNUT CELLS cell neutrope-
hypercalcemia otropism and pau- • ALK gene mutations may be • highly aggres- nia]
due to para- trier’s microabscess] seen→ good prognosis sive
neoplastic syn- • SEZARY SYN- • 5-year survival is >75% • EBV positive

/e
drome DROME • Drugs used: • Poor prognosis

,1
• Very aggressive • Exfoliative Eryth- ƒƒ CRIZOTINIB (ALK

• poor response roderma + Sezary inhibitor)

to treatment cells in peripheral ƒƒ BRENTUXIMAB (CD30

es
blood immunotoxin)

HODGKIN’S LYMPHOMA
ot
[ARISES FROM GERMINAL CENTRE OR POST GERMINAL CENTRE B CELLS]
N
CLASSICAL SUBTYPE LYMPHOCYTE
PREDOMINANT TYPE /
EE

NODULAR LYMPHOCYTE RICH MIXED LYMPHOCYTE

SCLEROSIS CELLULARITY DEPLETED NODULAR LYMPHOCYTE
[most common [most common HL [seen in old age and PREDOMINANT
M

subtype in world] subtype in India] HIV (+)patient]

• EBV negative • EBV positive • EBV positive • EBV positive • EBV negative
PG

• has LACUNAR • CLASSICAL REED • NUMEROUS • MANY REED • POPCORN CELLS/L-H

REED STERNBERG REED STERNBERG cells in background of
STERNBERG CELL background STERNBERG CELLS WITH very numerous lymphocytes
CELL has numerous cells surrounded few Lymphocytes • Lymphohistiocytic
y

• Male = Lymphocytes by Eosinophils, • poorest prognosis variant of RS cell

M

Females • Males > Females Lymphocytes [2018]

• CD-15/30 (+) • CD-15/ 30(+) and Histiocytes • CD 15/ 30 (-)
• good prognosis and CD-20 (-) • CD-15/ 30(+) • LCA, CD45 CD20
• good prognosis • intermediate positive
prognosis • best prognosis

346

zz Treatment- Chemotherapy (ABVD) + RT and Bone marrow transplant

notes
 My PG
MEE
Notes

Myeloid Neoplasm
Acute Myeloid Leukaemia

Presence of > 20% Myeloid blast in bone marrow on PS

Fab classification of aml
M0 AML minimally differentiable
M1 AML without maturation

Medicine
M2 AML with maturation
most common AML t(8:21) good prognosis, Soft tissue chloromas seen
M3 AML with maturation/ acute promyelocytic leukaemia
• two types:
ƒƒ hyper granular type→ large course granules in cytoplasm
with NUMEROUS AUER RODS called as “FAGGOT” cells

/e
ƒƒ micro granular type less common with fine granules

• diagnosis by t(15:17)→Chromosome 17 has RARA gene

,1
that is retinoic acid receptor Alpha which is important for
conversion of promyelocyte to Myelocyte→thus treatment is

es
all Trans retinoic acid
M4 Acute Myelomonocytic leukaemia ot
[2ND most common AML ]→Gum involvement present.
M5 ACUTE MONOCYTE/ MONOBLASTIC LEUKAEMIA
N
• 20% MONOBLAST
• PERIPHERAL BLOOD MONOCYTE COUNT > 1000μ/L
EE

• increased serum and urinary lysozyme levels

• The predominant promonocytes have abundant cytoplasm
with scattered MPO-negative azurophilic granules. The
M

nuclei are marked by delicate folds and creases. Nucleoli are

inconspicuous. (Wright-Giemsa stain)
PG

• Gum involvement present.

M6 acute erythroleukemia
• two types:
y

ƒƒ erythroid myeloid type > 20% myeloblast > 50% dysplastic

erythroblast
M

ƒƒ pure erythroleukemia > 80% erythroblast

ƒƒ Bone marrow smear from a case of erythroleukemia

showing a multinucleated erythroblast with megaloblastoid
nuclear chromatin. (Wright-Giemsa stain)
M7 acute megakaryoblastic leukaemia
ƒƒ 20% megakaryoblast in bone marrow or PS

ƒƒ Acute myelofibrosis

ƒƒ MC AML in down syndrome

zz Clinical Features: zz Treatment:

 Anemia, Thrombocytopenia and Neutropenia,  Chemotherapy- Cytarabine +
 Leucocytosis Etoposide
 MC organ involved- Brain, Bones are also involved  M3/ APML- ATRA and As2O3(in 347
resistant cases)
notes
 My PG
MEE
Notes

RENAL PATHOLOGY
zz Filtration Barrier is Glomerular membrane
zz It consists of:
 Podocyte
 Endothelial cell
 Basement membrane
zz Podocytes are Negatively charged thus
Repel negatively charged substances

Medicine
Ex:Albumin→thus not filtered

/e
,1
Renal failure
General principle:

es
• Rate of urea filtration of UREA and Creatinine ∝ GFR
• Rate of reabsorption of Urea ∝ 1/ GFR ot
• Normally BUN/creatinine is <15
UREA BUN .
N
Cause of Renal Failure GFR Creatinine
Absorption Reabsorption Overall CREATININE
Pre-renal causes:
EE

• Acute blood loss

• Cardiac failure ↓ ↓ ↑ ↑↑ ↑ >20
• Ischemia
M
PG

Renal causes: Glomerular cause ↓ ↓ ↑ ↑↑ ↑ >15

• Toxins
Renal tubular No reabsorption Q
• Drugs ↓ ↓ ↑ ↑ <15
Ischemia cause tubule is damaged
y

Post renal Initially ↓ ↓ ↑ ↑↑ ↑ >15

• Outflow
M

In long standing No reabsorption Q

Obstruction ↓ ↓ ↑ ↑ <15
case tubule is damaged

Differentiating Features of Prerenal and Renal disorders

INVESTIGATION PRERENAL RENAL

BUN/ Creatinine > 20 < 20
Urinary Na < 20 meq/L > 20 meq/ L
FeNa < 1% > 2%
Urine Creatinine/ Plasma Creatinine > 40 < 40
Urine osmolarity > 450 mOs/litre < 450 mOs/litre
Cast Normal/ Hyaline cast Granular cast 353

notes
 MEE
My PG
Notes

Acute Renal Failure Markers of

GFR status:
zz RIFLE ( Risk, Injury, Failure, Loss of Function, End-stage kidney disease) zz Cystatin C
criteria
zz Creatinine
zz Phases:
Newer Markers
 Phase 1 →initiation phase [lasts <48 hours] → Serum Creatinine > 1.5 of AKI:
times the normal
zz KIM-1
 Phase 2 → maintenance or Oliguric phase → Serum Creatinine > 2 times
the normal zz IL-18
Medicine

ff Lasts from 2nd to 10-14 days zz NGAL

ff fluid retention , Uremic complications, electrolyte imbalance zz Cystatin-C
ff dialysis should be initiated in this phase zz L-FABP
 Phase 3 →diuretic Phase → Serum Creatinine > 3 times the normal zz NAG
 Phase 4 →recovery phase
Markers of acute kidney injury: CLUSTERIN, osteopontin and alanine amino peptide

/e
zz

Chronic Kidney Disease

,1
Calciphylaxis
zz KIDGO- Kidney Disease Improving Global Outcomes

es
zz Seen in advanced CKD
 Classification of CKD
zz Due to hyperphosphatemia
 Uses GFR and Albuminuria to predict Prognosis of CKD
ot Calcium phosphate
zz
zz Stages:
deposited in vessels
Stage 1→ GFR 90 ml/min/1.73 m2 → Asymptomatic
N


 Stage 2→ GFR 60-89 ml/min/1.73m2

Stage 3→ GFR 30-59 ml/min/1.73m2 → Symptoms appear when GFR <50
EE



 Stage 4→ GFR 15-29 ml/min/1.73m2 →Anemia, Htn,Edema, etc.

 Stage 5→ GFR < 15 ml/min/1.73m2 → End stage renal disease, Electrolyte abnormality,
M

water intoxication (convulsions), etc.

PG

Dialysis

zz Indications:
Uremic pericarditis
y



Neurological manifestations
M



 refractory metabolic alkalosis

 refractory hyperkalimea
 volume overload
zz Types: Hemodialysis (Most commonly done) and Peritoneal Dialysis ( CAPD and CCPD)
zz By dialysis uremic manifestation improve except osteodystrophy and sexual dysfunction
zz On dialysis patient prone to develop aluminium toxicity which leads to dementia
zz MC acute complication on recurrent hemodialysis is hypotension
zz MC complication causing death in recurrent hemodialysis is cardiovascular complications

354

notes
 My PG
MEE
Notes

Nephrotic Syndrome Nephritic Syndrome

zz Proteinuria > 3.5 mg/day zz Proteinuria < 3.5/day
zz Na- water retention→ Severe edema zz Mild edema
zz Immunoglobulins decrease→ Infections zz Hematuria present
zz thrombosis present

Medicine
/e
,1
es
ot
N
EE

Nephrotic Syndrome
M

Minimal Change Disease/ Lipoid Nephrosis

PG

zz MC nephritic syndrome in children

zz Causes: Idiopathic, Hodgkin’s disease, Insect bite, NSAIDs and Allergy
Pathology:
y

zz
No changes seen on light microscopy
M



 Effacement of Foot processes in e- microscopy

zz Treatment: Steroids, Cyclophosphamide (Steroid dependent cases) and Tacrolimus(steroid
resistant cases

Membranous Nephropathy

zz CAUSES:
 Idiopathic
 Carcinomas- Lung, Breast, Ovary and colon
 Infection- Hep B, Malaria, Syphilis, Leprosy,
Schistosomiasis
 Drugs-NSAIDs, Penicillamine, ACE inhibitors
355
Figure:  Diffuse thickening of the glomerular basement
membrane in MGN
notes
 MEE
My PG
Notes

 Paraneoplastic syndrome
 Diabetes
 Autoimmune diseases- SLE and RA
zz Pathology:
 Light microscopy → Irregular GBM thickening → SPIKED BM
 e- microscopy → Subepithelial deposits
 Immunofluorescence → SPIKE AND DOME Pattern
zz Membranous Phospholipase A2 Marker levels are raised in blood
zz Most common cause of thrombosis associated with Nephrotic syndrome.
Medicine

zz Treatment: Steroids + Cyclophosphamide/ Cyclosporin

zz May progress to ESRD

Focal Segmental Glomerulosclerosis [FSGS]

MC type of Nephrotic syndrome in Adults

/e
zz

zz Causes are: DM, Heroin abuse, HIV, IgA/Htn/Reflux

,1
nephropathy , SCD
zz Pathology:

es
 On LM→ focal segmental sclerosis of Mesangium
 e- microscopy → Effacement of Foot processes ot
 Su-PAR Marker levels are raised in blood
 Immunofluorescence → negative
N
 Collapsing type specially in HIV patients
zz Treatment: Steroid Figure:  Accumulations of matrix material in
EE

glomerulus in FSGS
Diabetic Glomerulosclerosis
M

zz Presents with microalbuminuria(stage 3)

Diffuse Glomerulosclerosis is common but Focal
PG

zz

Glomerulosclerosis is characteristic
zz Pathology:
 PAS Positive Kimmelstiel Wilson LESION (MC in type
y

1)
M

 nodules contain Trapped MESANGIAL CELLS

 Fibrin caps and capsular drops in Bowman’s capsule
 Armani ebstein deposits in Tubules
zz Treatment:
Figure:  Kimmelstiel Wilson lesion in diabetic
 Blood sugar control, ACE inhibitors
glomerulosclerosis
 End stage → Dialysis/ Transplant

MPGN

zz Less commonly MPGN also presents as Nephrotic syndrome

356

notes
 My PG
MEE
Notes

Infective Endocarditis
zz Mitral valves are MC valves involved in IE
zz Tricuspid valves are MC valves in IV drug abusers
zz Staph aureus is MCC of acute endocarditis
zz Modifies Duke's Criteria is used for Diagnosis:
Major criteria Minor criteria
• Positive Blood culture • predisposing heart conditions or injection drug use
• Evidence of endocardial • Fever > 38oC (> 100.4o F)

Medicine
involvement • Vascular phenomenon- Embolic episodes or infarct
• New valvular • Immunologic phenomenon- Roth spot, Osler nodes , RA factor
regurgitation • positive blood culture but not meeting major criterion as noted previously
zz Diagnosis- 2 Major or 1 major + 3 minor or 5 Minor
zz Treatment: antibiotics according to the causative organism

/e
Vegetations of Heart

,1
Infective endocarditis Libman sacs Nonbacterial thrombotic Rheumatic heart
endocarditis endocarditis disease

es
Friable vegetation Non friable Non friable Non friable
Bacteria present Sterile Sterile Sterile
ot
N
EE
M

Large irregular Small-medium sized Small-medium bland Small warty vegetations

PG

vegetations extends to on both sides of valve vegetations along the line of along the line of valve
cordae leaflets valve closure closure
Alphabetically I→L→N→R, Friable→non friable, Bacteria +→sterile and Big→small-medium→small
y
M

Cardiac Tumors
zz >90% tumors of heart are Malignant
zz Myxomas consist of stellate multinucleated cells
zz Rhabdomyoma consist of characteristic cells called Spider cells which have glycogen laden vacuoles
with strands of cytoplasm
zz MC tumor→ secondaries
zz MC 1o tumor→Myxoma
zz MC 1o for cardiac secondary→lungs>breast
zz MC site of Myxoma→Left Atrial
zz Mc 1o tumor in children→Rhabdomyosarcoma
371
zz MC 1o malignancy→Angiosarcoma

notes
 MEE
My PG
Notes

Cardiomyopathy

DILATED CARDIOMYOPATHY RESTRICTIVE HYPERTROPHIC OBSTRUCTIVE

CARDIOMYOPATHY CARDIOMYOPATHY
Patho- • Impaired Systolic function • Impaired Dystolic • Impaired Dystolic function
physiology function
Causes • Idiopathic, Alcohol, Familiall, • Amyloidosis • Congenital
Toxin • Sarcoidosis • In Athletes
• CTD • Genetic
Medicine

• Infections like Coxsackie Virus

• Chagas disease
• Doxorubicin, Chloroquine, ART
• Carcinoid
• Eosinophilic cardiomyopathy (endomyocardial
• Connective tissue disorders(CTD) fibrosis)
• Hemochromatosis
Findings • CXR- Cardiomegaly, • Dyspnea • Asymmetric septal

/e
• Heart failure, • Loud S3 hypertrophy- LV outflow
• ↓ Ejection fraction • Kussmaul sign (+) obstruction

,1
• Loud S3 +++ • Right heart failure • Angina, Syncope , Sudden
• CXR- cardiac death
Cardiomegaly • Banana shaped cavity of Left

es
ventricle
• Double/ triple apical impulse
• Diamond shaped murmur
ot enhanced by Valsalva
• Associated with MR
N
Management • Correct underlying cause • Diuretics • B blocker is drug of choice
• Inotropes • ACE inhibitor • CCB
EE

• Diuretics • B blocker • Septal myomectomy

• ACE inhibitor • Surgery • Dual chamber pacing
• B blocker
• ICD
M

Takotsubo/ Stress induced cardiomyopathy

PG

zz Also called as Broken hear t Syndrome/ apical ballooning

syndrome,
y

zz Temporary condition in which heart muscles suddenly become

M

STUNNED or Weakened [2018]

zz Clinical feature
 women >50 years of age, Common in Japanese
 Acute chest pain
 Triggered by an emotionally or physically stressful event
and may mimic acute MI
 ventricle shows global ventricular dilation with basal
contraction
zz Treatment-
 Nitrates, b blocker Intra-aortic balloon pumping
 Anticoagulation should be avoided

372

notes