Rabies diagnosis 

■■■■■■■■■■■■■■
Pathologically rabies is defined by presence of intracytoplasmic NEGRI BODIES in hippocampus, brain stem and
cerebellum.

● Best predictor of future Coronary artery disease or myocardial infarction (in descending order)
1) HsCRP(highly sensitive C Reactive Protein)
2)"TC (total cholesterol )/HDL " ratio
3) "Apo-B/ Apo-A" ratio.
4)LDL
5)Non HDL (Total cholesterol -HDL)
6)HDL

 Most common form of MODY is -----MODY type 3 (HNF 1 alpha )..

 For amyloidosisFat pad is better than rectal.

HODGKIN'S LYMPHOMA
Most common lymph node affected - cervical lymph node.
● WHO classification ( 2 types on the basis of Reed Sternberg cells)
A) CLASSICAL—(following 4 subtypes)
■ Best / most specific marker for RS cells ---- PAX-5 (>90%...latest info) > CD 30 (80 to 100% of classical HL). 
Other markers CD 15 ( 75-85% ).

2) NODULAR SCLEROSIS. 
• Most common HL (world)
• Mediastinal involvement most common in this HL.
• Male and female are equally affected ( other HL, males are more commonly affected)
• Lacunar reed Sternberg cells are seen (cytoplasmic lacuna formed due to tissue fixation artefact )
• “Collagen Bands” are forming nodules in Lymph nodes.
2) MIXED CELLULARITY
• Most common HL in India
• Maximum RS cells are seen.
3) LYMPHOCYTE DEPLETED.
• Least common type of HL
• RS cells (various names) ---pleomorphic / Mummified / necrobiotic
• Worst prognosis
4) LYMPHOCYTE RICH
• Minimum RS cells are seen.
B) LYMPHOCYTE PREDOMINANT
• Popcorn RS cells (or lympho - histiocytic (L&H ) RS cells )
• Immunophenotyping- CD 20 (=BCL6+ve), CD 45, CD 79a, EMA (Epithelial Membrane Antigen)
• Best prognosis amongst all HL.
#HIGH yield info about HL:-
• EBV and HIV infections ,both are most commonly a/w(amongst Hodgkins lymphoma subtype)----MIXED
CELLULARITY (HODGKINS LYMPHOMA)
• HIV associated Hodgkins Lymphomas are ----
mixed cellularity (most common)
nodular sclerosis and 
lymphocyte depleted
• EBV not associated with HL—
1) Nodular sclerosis
2) lymphocyte predominant

RHEUMATIC FEVER---Least commonly affected Valve is--- pulmonary 

● Most common malignancy in HIV---KAPOSI SARCOMA..

● Most pathognomonic/diagnostic of Rheumatic Heart Disease is "ASCHOFF BODIES"

■ NOTE

( Its not ANTISCHKOW CELLS …..

Please read that sentence of robbins carefully ...we are mistaking it on interpretation__(Robbins 9/e is right and
saying ASCHOFF BODIES are pathognomonic ;not for Antischkow cells (READ MY EXPLANATION and see the
OTHER REFERENCES GIVEN with their links) ---
●●●●●●●●●●●●
EXPLAINATION
●●●●●●●●●●●●●●●
(exact language of Robbin's 9th ed, pg 558)-------“ Distinctive lesions occur in the heart, called Aschoff bodies,
consisting of foci of T lymphocytes, occasional plasma cells, and plump activated macrophages called
Anitschkow cells (pathognomonic for RF).”

..here author is beginning with Distinctive lesion (means pathognomonic), called aschoff bodies ,,,,and then
describing about its contents and closing it with a bracket saying ..(pathognomonic for RF)…its for--- aschoff
bodies ; not for Antischkow cells,,which everyone is assuming it for antisckow cells (reason of confusion) ....it is
part of aschoff bodies.
■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■
STANDARD REFERENCES TO END THIS CONFUSION…..

• Most common cause of PAPILLARY NECROSIS (=Necrotising Papillitis)----DIABETES MELLITUS 

Fetal Haemoglobin (HbF) level will reach <2% at age of 30 weeks (7 months approx.).

skin pigmentation in hemochromatosis is due to-----MELANIN (Predominantly) and hemosiderin (minority)

Size of donor and recepient organ doesnt matter in kidney transplantation.

• HLA-D is most important) for organ transplantation and tissue typing because they are having more no. of
polymorphic gene
HLA-D is most important because they are having more no. of polymorphic gene….order of importance is is HLA-
DR>B>A.

#Most common malignancy in HIV is Kaposi sarcoma.

#Most common site for Kaposi sarcoma is SKIN of feet.

#Most common extracutaneous site is Lymph nodes.

#Most common site in Gastrointestinal tract is Duodenum (small Intestine)

SPLEEN TUMOURS :-
1) most common primary for splenic metastasis--- -----mc is Melanoma) (table 59-2 page 470 Harrison 18th
edition)

( NOTE) :- 
• for isolated mets(means mets foci is only in spleen and not in other organs)---mc primary is ovarian tumours
• for metastses(usually many other organs are also involved simultaneously) -----mc is Melanoma) (table 59-2
page 470 Harrison 18th edition)

2) Mc primary malignant splenic tumor------lymphoma (MARGINAL ZONE B CELL LYMPHOMA). 

3) Mc tumor of spleen--HEMANGIOMA

#SPLEEN-CYST
1) Most common (60-70%)-----due to parasitic infection with Echinococcus granulosus (hydatid disease.) 
2) Most common Non-parasitic cysts ----pseudo cysts secondary to trauma

"PLASMA CELL DISORDERS"

■■■■■■■■■■■■■■■■■■■■■■■■

A) MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS):- 

------------------------------------------------------------------
( diagnostic criteria)
1. Serum paraprotein < 3 g/dl AND
2. Clonal plasma cells <10% on bone marrow biopsy AND
3. NO myeloma-related organ or tissue impairment

●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
B)ASYMPTOMATIC /SMOULDERING MYELOMA:- ( diagnostic criteria)

1) Serum paraprotein >3 g/dl AND/OR

2) Clonal plasma cells >10% on bone marrow biopsy AND
3) NO myeloma-related organ or tissue impairment

●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
C) MULTIPLE –MYELOMA:-
• International Myeloma Working Group (2009;latest criteria)

• SYMPTOMATIC MYELOMA:

A) Clonal plasma cells >10% on BONE MARROW BIOPSY or (in any quantity) in biopsy from other tissues
(PLASMACYTOMA)
B) A monoclonal protein (paraprotein) in either serum or urine (except in cases of true non-secretory myeloma)
C) Evidence of end-organ damage related to plasma cell disorder (related organ or tissue impairment, ROTI,
commonly known by acronym "CRAB"):
1) HyperCalcemia (corrected calcium >11.5mg/dl )
2) Renal insufficiency attributable to myeloma ( serum creatinine > 2 mg /dl)
3) Anemia (hemoglobin <10 g/dL)
4) Bone lesions (lytic lesions or osteoporosis with compression fractures)
NOTE: 
4) Recurrent infections alone in a patient who has none of CRAB features is not sufficient to make the diagnosis
of myeloma.
5) Patients who lack CRAB features but have evidence of amyloidosis should be considered as amyloidosis and
not myeloma. 
6) CRAB like abnormalities are common with numerous diseases, and it is imperative that these abnormalities
are felt to be directly attributable to the related plasma cell disorder and every attempt made to rule out other
underlying causes of anemia, renal failure etc.
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●

D) PLASMA CELL LEUKEMIA:- (WHO criterion)

in peripheral blood:-
1) plasma cells more than 20% of cells
2) absolute plasma cell count of more than 2 × 109/L. 

●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
POOR PROGNOSTIC FACTORS FOR MULTIPLE MYELOMA:-
1) Serum Beta-2-Microglobulin > 6 mg/dl
2) C-REACTIVE protein >6 mg/dl
3) presence of plasmablastic morphology
4) Bone Marrow biopsy---“ diffuse”-pattern ; prominent “ANGIOGENESIS”
5) serum LDH raised
6) plasma cell labelling index>3%
7) serum creatinine > 2 mg/dl
8) cytogenetics:-
deletion of --- 13q; 11q; 17p; monosomy 13; HYPODIPLOIDY.

●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
This criteria is not used nowdays (just for EXAM point of view)
A) MAJOR CRITERIA
1. Plasmacytomas on tissue biopsy
2. Bone marrow plasmacytosis (> 30% plasma cells)
3. Monoclonal immunoglobulin spike on serum electrophoresis: IgG > 3.5 g/dL or IgA > 2.0 g/dL; 
4. kappa or lambda light-chain excretion > 1.0 g/d on 24-h urine protein electrophoresis.
B) MINOR CRITERIA
a. Bone marrow plasmacytosis (10–30% plasma cells)
b. Monoclonal immunoglobulin spike present but of lesser magnitude than given above
c. Lytic bone lesions
d. Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
NOTE:-
Any of the following sets of criteria will confirm the diagnosis:
3) Any two major criteria
4) Major criterion 1 plus minor criterion b, c, or d
5) Major criterion 3 plus minor criterion a or c
6) Minor criteria a, b, and c, or a, b, and d

Most common cause of renal failure in multiple myeloma is ----Light chain deposition >>>>hypercalcemia.

BLOOD- BANKING
■■■■■■■■■■■■■■■■■

• SAGM additive solution provides 

optimum red Cell viability

1) Sodium Chloride provides isotonicity

2) Adenine maintains ATP for red cell viability
3) Glucose supports red cell metabolism (Nutrition)
4) Mannitol helps reduce red cell lysis

• SHELF LIFE (WHOLE BLOOD / RED CELLS ) IN :

1) ACD( acidified citrate dextrose) = 21 days 

(> 70% transfused cells viable after 24 hours) 
2) CPD( Citrate phosphate dextrose) = 28 days 
3) Citrate Phosphate Dextrose Adenine (CPDA) = 35 days
4) SAGM ( Saline Adenine Glucose Mannitol)= 42 days
• Whole blood:
Storage temp.= 2-6 0c
1 unit raises Hb by ---1gm/dl and haematocrit by 3%.

9. After collection from donor ,blood should be processed for component separation within 6 hrs
• Storage and duration
1) Whole blood / packed red cells--- 2-6 0c for 42 days
2) Platelets----22-24 0c for 5 days with continuous agitation
3) Fresh frozen plasma---below -18 degree c for 1 year
4) Cryoprecipitate------ below -18 degree c for 1 year
• Transfusion protocols:
Transfusion should commence within 30 minutes of removing blood bag from refrigerator of blood bag.
(after that it will increase risk of bacterial contamination)

1) Whole blood /packed rbc --transfusion must be completed within 4 hrs.

2) Platelet and FFP----within 20 minutes.
Transfusion set should have standard filter of 170 micron meter pore size
Usual needle size =18-19 gauge
Not necessary to warm blood before transfusion
Patient should be monitored during 1st 15 minutes, following this every hour, at the end and after 4 hrs after end
of transfusion.

***************************************

• MASSIVE BLOOD TRANSFUSION 

defined as 
1) adults
a) replacement of >1 blood volume in 24 hours ,or 
b) >50% of blood volume in 4 hours (adult blood volume is approximately 70 mL/kg).
2) children, 
• transfusion of >40 mL/kg (blood volume in children over 1 month old is approximately 80 mL/kg).
electrolyte abnormalities are 
1) hypocalcemia 
2) hypomagnesemia 
3) hypokalemia
4) hyperkalemia
5) metabolic alkalosis ( due to excess citrate is converted to bicarbonate in liver)
Bleeding following massive transfusion can occur due to hypothermia, dilutional coagulopathy, platelet
dysfunction, fibrinolysis, or hypofibrinogenemia. 
Transfusion of 15 to 20 units of blood products causes dilutional thrombocytopenia
Massive bloodTransfusions 
Initially TRANSIENT HYPERGLYCEMIA due to glucose in preservatives;
this leads to insulin release and may cause HYPOGLYCEMIA
Overall most commonly--- HYPOGLYCEMIA > HYPERGLYCEMIA
***********

TRALI (Transfusion-Related Acute Lung Injury) is the most common cause of major morbidity and death after
transfusion. It presents as an acute respiratory distress syndrome (ARDS) either during or within 6 h of
transfusion.

SEROLOGY OF HEPATITIS B:-

1) HBsAg—
considered to be infected ( can be acute/chronic or carriers)
Persistence of HBsAg is used to differentiate acute from chronic infection. 
Presence of the antigen longer than 6 months after initial exposure indicates chronic infection.

2) anti-HBs—
implies either active or passive immunization that usually persists for life.
Protected

3) Anti-HBc— (NOTE:- HbcAg is not detectable in serum)

first detectable antibody
IgM anti-HBc indicates acute infection.( most reliable marker of acute hepatitis infection)
only serologic marker detectable during the “window period “ .
IgG anti-HBc indicates previous or ongoing infection.

4) HbeAg
High infectivity and active disease
higher rates of viral transmission
marker of viral replication and infectivity ( HbeAg----produced only during replication of the virus)

5) anti-HBe:
low infectivity.
Loss of HBeAg and appearance of anti-HBe in serum is called “seroconversion”
Indicates clinical improvement (=remission of the disease)

6) HBV DNA (quantitative viral load)

indicates viral burden and viral replication
assess recovery from infection and candidacy for antiviral therapy 
to differentiate between inactive carrier state and chronic active hepatitis in chronic HBV infection. 

■ cutoffs for consideration for antiviral therapy is

A) HbeAg-positive patients with chronic hepatitis -----100,000 copies/mL (or 20,000 IU/mL) 
B) HbeAg-negative patients---10,000 copies/mL ( or 2,000 IU/mL ) 
NOTE:-
A) imp info :-
1) Qualitative marker of HBV-replication-----HbeAg
2) Quantitative marker of HBV-replication:-
Definitive is HBV-DNA >HBV-DNA polymerase 
B) INACTIVE CARRIERS 
Refers to HBeAg-negative with normal serum ALT levels and low (< 2000 IU/mL) or undetectable HBV DNA.

C) precore or basic core mutant HBV

also referred to as HBeAg-negative, or anti-HBe-positive HBV
HBeAg-negative and anti-HBe-positive patients with high serum HBV-DNA levels (>10000 copies /ml) and
persistent or intermittent elevations in alanine aminotransferase (ALT) activity
represents severe and progressive form of liver disease
associated with frequent development of cirrhosis and HCC.

• MOST COMMON CAUSE :

#Of nephritic syndrome :
●●●●●●●●●●●●●●●●●●●
■ 'P'edia = 'P'SGN
■ 'A'dults= ig 'A'

■ over'A'll = ig 'A'

#Nephrotic- syndrome:
●●●●●●●●●●●●●●●●●
■ children=mcd 
■ adults=fsgs
■ old age=membranous
■ overall=fsgs
IMMUNOTACTOID GLOMERULOPATHY
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●

(immuno”--- means related to immune system; “tactoid”------ means group of rod-like structures.)
Idiopathic mostly
Age > 50 yrs
Most patients are a/w lymphoproliferative disease. ( Both leukemias and lymphomas) 
They often have nephrotic syndrome.
May have high blood pressure (or hypertension) at the time of diagnosis
ELECTRON MICROSCOPY( DIAGNOSTIC) 
• distinct pattern of groups of rod-like structures arranged in lines, similar to stack of pipes or logs. 
• rod-like structures are called microtubular structures ( these rod-like structures contain immunoglobulins mainly
of monoclonal IgG type and complements.)
• Congo red-negative organized deposits on renal biopsy.
• have poor prognosis

"CHRONIC NEUTROPHILIC LEUKEMIA" criteria...

●●●●●●●●●●●●●●●●●●●●●●●●●●●
1)Philadelphia negative
2)blasts <1%
3)immature granulocytes <10%
4)Peripheral blood leucocytosis >25×109...with neutrophil and band forms >80%

(GLOBOCAN 2012 fact sheet/latest)

■■■■■■■
WORLD
■■■■■■■
Most common cancer
A) MALE

1) Incidence---Lung cancer
2)Mortality---Lung cancer

B)FEMALE

1)Incidence----Breast ca
2)Mortality----Breast cancer

C) OVERALL
● Most common incidence and mortality both---Lung cancer

■■■■■■■■■
INDIA
■■■■■■■■■

Most common cancer

A)MALE
1) incidence ---oral cancer
2) Mortality----Lung cancer

B)FEMALE
● Incidence and mortality both --Breast cancer
C) OVERALL
● mortality and incidence both--Breast cancer
INHERITANCE OF HYPERBILIRUBINEMIA:
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●

1) CONJUGATED HYPERBILLIRUBINEMIA:
Dubin Johnson syndrome: AR
Rotar syndrome: AR
2) UNCONJUGATED HYPERBILLIRUBINEMIA:
Crigler Najjar syndrome type 1: AR
Crigler Najjar syndrome type 2 : AR>AD
Gilbert syndrome: AD>AR

• Pancoast tumor is most commonly associated with ----Squamous cell carcinoma of lung.

LEUKEMOID REACTION
■■■■■■■■■■■■■■■■■■
Persistent leukocytosis above 50,000 cells/mm3 when the cause is other than leukemia defines a leukemoid
reaction.
major causes of leukemoid reactions are 
• severe infections,
• intoxications
• malignancies, 
• severe hemorrhage
• acute hemolysis. 
• Trisomy 21 ( down syndrome)
• Asplenia
• Diabetic ketoacidosis

1) CLINICALLY organomegaly seen in CML but not in leukemoid reactions.

2) The peripheral blood smear may show myelocytes, metamyelocytes, promyelocytes, and rarely myeloblasts;
( significant increase in early neutrophil precursors) however, there is a mix of early mature neutrophil precursors,
IN CONTRAST TO THE IMMATURE FORMS TYPICALLY SEEN IN ACUTE LEUKEMIA. 
3) Serum leukocyte alkaline phosphatase is elevated in leukemoid reaction (DEPRESSED IN CHRONIC
MYELOGENOUS LEUKEMIA.)
4) Basophilia ,eosinophilia and thrombocytosis favors CHRONIC MYELOID LEUKEMIA but these are absent in
LEUKEMOID REACTIONS.

High yield info

1)Most common benign tu of esophagus----Leiomyoma
2) Most common malignancy esophagus----Squamous cell carcinoma
3)Mc benignt tumor of stomach is ----epithial polyps 

4) Mc site of leiomyoma in git is----- stomach

5) Mc malignancy of small intestine is---- adenocarcinoma

6) Mc benign tumor of small intestine is -------adenoma

7) Mc symptomatic benign tumor of small int is ------leiomyoma

 #END of Controversy
---------------------------------
• Cause of edema in Nephrotic Syndrome---- sodium water retention >>>> Hypoproteinemia

----------------------------------------------------------------------------
Reference---
1) Brenner and Rector’s The Kidney--- Maarten W. Taal, Glenn M. Chertow, Philip A. Marsden, Karl Skorecki,
Alan S. L. Yu, and Barry M. Brenner (9th edition published by Elsevier)
------------------------------------------------------------------------------------------
Highlights _____
• Edema is a major characteristic of nephrotic syndrome. 
A) UNDERFILL MECHANISM OF SALT AND WATER RETENTION 
• hypoalbuminemia reduces the oncotic pressure within the capillaries, and this favors the net translocation of
fluid into the interstitial spaces.
• To the extent that this occurs, intravascular volume and blood pressure fall, and this triggers the sympathetic
nervous system, activates the renin-angiotensin-aldosterone axis, elevates vasopressin levels, and modulates
many other control systems that act together to promote net renal salt and water retention.
• This pathogenic sequence has been termed the underfill mechanism of salt and water retention in nephrotic
syndrome. 
• 
B) OVERFILL MECHANISM. 
• However, edema formation in many, PERHAPS MOST, NEPHROTIC PATIENTS CANNOT BE FULLY
EXPLAINED BY UNDERFILL MECHANISMS. 
• Although reduced intravascular oncotic pressures certainly exist in nephrotic patients, the net hydrostatic
gradient for water movement across capillary beds is also influenced by the interstitial oncotic pressure, and this
generally falls in parallel with reductions in plasma oncotic pressure. 
• Consequently, the net hydrostatic pressure gradient from the intravascular compartment to the interstitial space
may not significantly increase. Edema formation under these conditions may be the consequence of a primary
form of renal salt and water retention. This pathogenic sequence for edema formation is called the overfill
mechanism. “”””
NOTE____Undoubtedly each of these mechanisms plays a role in various phases and forms of nephrotic
syndrome. these mechanisms may evolve from one form to the other.

CHLOROMAS (=GRANULOCYTIC SARCOMAS) are most commonly a/w translocation---t(8:21) and AML-M2.

Most common site and “PRIMARY site” for CONGENITAL TB --- LIVER

VASCULITIS:-

1) most common vasculitis in paeditrics age group is ----HSP ( HENOCH SCHONLEIN PURPURA )
references—
2) most common vasculitis in adults is – Giant cell arteritis (Temporal arteritis)
3) MOST COMMON vasculitis causing death in pediatric patient is -----kawasaki syndrome ( due to coronary
arteritis.)

■■■■■■■■■■■■■■■■■■■■■■■■
● Most common cause of PAPILLARY NECROSIS (=Necrotising Papillitis)----DIABETES MELLITUS 

*****Most common site for amebiasis is --Caecum.

IMMUNOLOGICAL CLASSIFICATION of ALL(acute lymphoblastic leukemia):-
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
A) B-cell precursor (CD19+ and/or CD79a+ and/or CD 22+)
1) Pro-B-ALL---no expression of other B cell marker
2) Common ALL--- (CD-10+,cytoplasmic IgM-ve)
3) Pre-B-ALL--- (Cytoplasmic IgM+ve)
4) Mature B-ALL---- ( surface Ig+ve)
B) T-cell precursor ( cytoplasmic CD3+,CD7+)
1) Pro-T-ALL--(no expression of other T-cell markers )
2) Pre-T-ALL (CD 2+ve and/or CD5+ve)
3) Cortical –T-ALL (CD1a+ve)
4) Mature-T-ALL (membrane CD3+ve)

■■■■■■■■■■■■■■

1) BASOPHILIC STIPPLING 

is ribosomal inclusions in RBCs and stained by ROMANOWSKY STAIN but not stained by PERL'S PRUSSIAN
BLUE STAIN (its for iron)
sideroblastic anemia, lead poisoning, megaloblastic anemia, thalassemia, Arsenic poisoning
constant finding of thalessemia

2) PAPPENHEIMER BODIES 

are iron deposits,

seen in SIDEROCYTES (siderocytes are intraerythrocytic PERL'S PRUSSIAN BLUE STAIN positive iron
granules)
seen in----- sideroblastic anemia, hemolytic anemia, and sickle cell disease

3) HEINZ BODIES 

are precipitated hemoglobin seen with special stain (He for Heinz and He for Hemoglobin)
seen in --- G6PD deficiency anemia, drugs like primaquine and dapsone, fava beans

4) HOWELL JOLLY BODIES

are DNA remnants

seen in------sickle cell autosplenectomy; severe hemolytic anemia, megaloblastic anemia, hereditary
spherocytosis, and myelodysplastic syndrome (MDS)

■■■■■■■■■■■■■■■■■■■■■■■

PYROPTOSIS
■■■■■■■■■■■■■■■■■■■■■■■■
form of programmed cell death associated with antimicrobial responses during inflammation.
initiation of pyroptosis is caused by the recognition of flagellin components of Salmonella and Shigella species
(and similar pathogen-associated molecular patterns (PAMPs) in other microbial pathogens) by NOD-like
receptors (NLRs). 
(NOTE------NOD-like receptors (NLRs). 
These receptors function like plasma membrane Toll-like receptors (TLRs), but recognise antigens located within
the cell rather than outside of it.)
In contrast to apoptosis, pyroptosis requires the function of the enzyme caspase-1 and Caspase -11.
caspase-1 is activated during pyroptosis by a large supramolecular complex termed the pyroptosome (also
known as an inflammasome containing IL-1 cytokine)
Pyroptosis differs from Apoptosis by following features (that’s why they are considered as NECROSIS ----
“Caspase dependent programmed cell death” )
a) Shows cell swelling
b) Cell membrane damage
c) Presence of inflammation

■■■■■■■■■■■■■■■
( SURE-SHOT for DNB/AIPG)---- (Robbins 9/e)

NECROPTOSIS: ( hybrid of Necrosis+Apoptosis but considered as NECROSIS)

• Also known as programmed cell death without caspase activation 
• It is both pathological (ischaemic brain injury, neurodegenerative diseases and viral infections ) and
physiological ( formation of mammalian bone growth plate )
• Under conditions that are insufficient to trigger apoptosis, TNFα activates TNFR1 and in turn induces the
recruitment of RIP1and RIP3 kinase and other proteins to form complex (which includes RIP1, RIP3, caspase
8 ). 
• formation of this complex leads to necroptosis (caspase 8 is not activated here in this pathway)
• Necroptosis differs from Apoptosis by following features (that’s why they are considered as NECROSIS ----
“Caspase independent programmed cell death” )
1) Shows cell swelling
2) Cell membrane damage
3) Presence of inflammation

■■■■■■■■■■■■■■
NEURONAL MIGRATION DISORDER (NMD) :-
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
• heterogenous group of disorders caused by the abnormal migration of neurons in the developing brain and
nervous system. 
• DCX( double-cortin gene), LIS1, and filamin1 genes are muatant
• Neuronal migration occurs during --- 12 TO 16 WEEKS of gestation
• structural abnormalities found in NMDs include 
1) schizencephaly, 
2) porencephaly, 
3) lissencephaly,
4) agyria, 
5) macrogyria, 
6) polymicrogyria, 
7) pachygyria, 
8) microgyria,
9) micropolygyria,
10) neuronal heterotopias (including band heterotopia), 
11) agenesis of the corpus callosum, 
12) agenesis of the cranial nerves.
DIAGNOSIS :-
by MRI scan (shows a characteristic appearance of absent or abnormal areas of brain tissue. )

■■■■■■■■■■■■■■■■■■
(This language would be the real twist in exam)

■ Most common appendix neoplsam---CARCINOID.

■most common malignant neoplasm of appendix --Mucinous adenocarcinoma

■■■■■■■■■■■■■■■■■■
SOFT TISSUE TUMOUR:
■■■■■■■■■■■■■■■■■■
1) Most common soft tissue tumour of childhood and adolescence--- rhabdomyosarcoma ( embryonal type)
2) Most common soft tissue tumour of adults-----lipoma
3) mc malignant soft tissue tumour of adults ----liposarcoma.
Most common site of SARCOMAS --- EXTREMITIES (lower> upper) >>>>>retroperitoneum
■■■■■■■■■■■■■■■■■■■■■■■■■■■■
IMPORTANT TRANSLOCATIONS:-
1) (EWS-ETV1) / EWS-ERG--EWINGS SARCOMA...
2) EWS-CHN--MYXOID CHONDROSARCOMA...
3) EWS-ATF-1--CLEAR CELL SARCOMA....
4)EWS-WT-1---DESMOPLASTIC SMALL CELL TUMOUR
■■■■■■■■■■■■■■■■■■■■
RHABDOMYOSARCOMA:
■■■■■■■■■■■■■■■■■■■■
● Sarcomas arise from skeletal muscle progenitors
● two most common forms are 
1) embryonal rhabdomyosarcoma (more common in younger children )
botryoid variant of ERMS arises in mucosal cavities, such as the bladder, vagina, nasopharynx, and middle ear. 
● Mc site –head and neck ( orbit) 
2) alveolar rhabdomyosarcoma. (more common in older children and teenagers)
● extremities are most common sites
associated with t(2;13) or t(1;13).
●Overall . embryonal rhabdomyosarcoma is most common
● LIGHT MICROSCOPY
rhabdomyoblasts looks like--- round, strap, racquet, and spider forms. 
●Rhabdomyoblasts shows muscle striations
● IHC :positive for intermediate filaments ---- desmin, vimentin, myoglobin, actin, myoD and myogenin
●all sarcomas follow HEMATOGENOUS route of metastases EXCEPT for alveolar rhabdomyosarcoma. ( which
follows LYMPHATICS route)
■■■■■■■■■■■■■■■■■
Lymphangiosarcoma :
■■■■■■■■■■■■■■■■■■■
● rare malignant tumor
●most commonly occurs in long-standing cases of primary or secondary lymphedema. 
●involves either the upper or lower lymphedemateous extremities( most common in upper extremities )
● lymphangiosarcoma is classically seen in upper extremity lymphedema occurring after mastectomy (Stewart-
Treves syndrome)

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● Blood group " Rh typing " is associated with chromosome 1p.

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MACROPHAGES:-
A) CLASSICALLY ACTIVATED MACROPHAGES (=M1)
Involved in inflammation e.g microbicidal actions ; phagocytosis; killing microorganisms
Examples are ---IL-1;2;6;8;TNF;IFN etc.

B) ALTERNATIVELY ACTIVATED MACROPHEGES (=M2)

Has - ANTI-INFLAMMATORY cytokines :
1) IL-4;
2) IL-10;
3) IL-13 
4) TGF( transforming growth factor)-BETA 
Function--- wound repair and fibrosis
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SEMAPHORIN
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● A membrane proteins that act as axonal growth cone guidance molecules.
● important in neural system development.
● main receptors for semaphorins are plexins.
● FUNCTIONS:- apoptosis, tumorigenesis, angiogenesis, neurodegenerative disease and axonal regeneration.

●MARKER OF
1)semaphorin 3a:- 
a) marker for disease activity and potential immunoregulator in SYSTEMIC LUPUS ERYTHEMATOSUS.
b) Alzheimer's disease (AD)
2) schizophrenia
3) parkinsonism

KLINEFELTER SYNDROME____
1)Most common cancer-----breast cancer
2) most common germ cell tumour --- (ExtraGonadal >gonadal) both places Teratoma is most common.

 Best IHC marker for Multiple Myeloma--- Cyclin-D1.

ASTHMA
--------------
1) Strongest and most consistent associations with asthma or allergic disease is associated with IL13 gene
polymorphism.

2) Increased serum levels and lung expression of YKL-40 (a chitinase like glycoprotein) are correlated with
disease severity, airway remodeling, and decreased pulmonary function.

HLA and MALARIA;

1) HLA-B53 --- protect against severe falciparum malaria
2) HLA-DRB1*04 was associated with severe malaria

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• “Revised Ghent criteria ”
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It is currently used for clinical diagnosis of Marfan syndrome. 
It considers : 
a) Family history
b) Cardinal clinical signs in the absence of family history 
c) Presence or absence of Fibrillin mutation.

CHEMOTHERAPY INDUCED MYELOSUPPRESSION 

order for susceptibility is 
PMN>PLATELET.>RBC..

Number of neurofibrillary tangles correlates better with the degree of dementia than does the number of neuritic
plaques.
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■ Most common renal disorder associated with leprosy is (descending order)

---secondary amyloidosis>mesangiocapillary GN >Mpgn1>>>membranous GN.

Serum biomarkers of brain injury can potentially measure injury to

a) neurons (neuron-specific enolase),
b) astrocytes (S100b) ----"best marker for brain injury "
c) axons (myelin basic protein). 
d) retinol binding protein 4 [RBP4])

••••••••••••••••••••••
• Most sensitive n specific tumour marker for hepatocellular carcinoma---ARGINASE-1.
(Arginase-1> hep per1> Glypican-3> pivka> alfa feto)

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■Most common blood vessel involved with Takayasu arteritis is "Subclavian artery"

■ Most common cause of chronic hepatitis ---Hepatitis C.

■Most common cause of carrier ---Hepatitis B 

■Most common cause of fulminant hepatitis --Hepatitis D

Bone marrow cellularity (Rubins pathology pg no 868)

●●●●●●●●●●●●●●●●●●●●●●●●●●
● Fat cells :Bone marrow cells =1:1
● Myeloid:Erythroid ratio=3:1
● Fat cells :RBC ratio=4:1

Glucocoticoid induces apoptosis.

#Certain infections have been associated with MALT lymphomas:

1) H. pylori infection ----- gastric MALT lymphomas.

2) Chlamydia psittaci-------- ocular adnexal lymphomas.

3) Borrelia burgdorferi ---- skin MALT lymphomas.

4) Campylobacter jejuni------ small bowel MALT lymphomas.

■ Pleuripotency of embryonic stem cell depends on expression of following 4 transcription factors:
1) Oct3/4
2) Sox 2
3) C-Myc
4) Kfl 4
■ Pleuripotency of embryonic stem cell is inhibited by homebox protein “Nanog” .

• Riboflavin (vitamin B2 ) deficiency causes circum corneal congestion.

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1) Superior vena cava syndrome is most commonly due to ---- malignancy ( Most common is ---Small Cell
carcinoma of lung )

2) Pancoast tu is most commonly due to ----Squamous cell ca of lung

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Myasthenia gravis is most commonly associated with thymic hyperplasia (65%).

#Disorders associated with ADVANCED PATERNAL AGE include :-

1) achondroplasia (a type of dwarfism)
2) neurofibromatosis
3) Marfan-syndrome
4) osteogenesis imperfecta (“brittle bone” disease)
5) klinefelter syndrome

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TUBERCULOSIS
●●●●●●●●●●●●●●●
● a/k/a KOCH’s disease
● acid fastness – due to MYCOLIC ACID
● Virulence factor --- “CORD factor”
a) PRIMARY TUBERCULOSIS
●●●●●●●●●●●●●●●●●●●●●●●
●Most commonly seen in children
● a/w unsensitised and unexposed individuals
●source of organism--- exogenous
● most commonly starts as “LATENT DISEASE”
● unilateral hilar lymph enlargement
■ GHON’S FOCUS:- 
**********************
● Subpleural fibrocaseous lesion (CONSOLIDATION) of lung parenchyma.
● microscopically contains epitheloid granulomatous inflammation
■GHON’S COMPLEX:-
**********************
●Consists of Subpleural ghon’s focus and involved lymph nodes.
●Ghon's complex found below clavicle.
■RANKE’S COMPLEX :-
***********************
● Ghon’s focus alongwith FIBROSIS and CALCIFICATION known as RANKE’S COMPLEX.

●Calcification
●Pleural effusion
●Erythema nodosum
● Phlyctenular conjunctivitis
b) POST-PRIMARY
(=SECONDARY)PULMONARY TUBERCULOSIS
●●●●●●●●●●●●●●●●●●●●●●●●●
● Seen in previously sensitized host due to reactivation of latent primary lesions
● frequently a/w decreased immune status
■PUHL’S LESION:-
********************
● Lesion in lung apex.
● No lymph node involvement
■ SIMON FOCUS 
*******************
● it is a tuberculous (TB) nodule formed in lung apex. 
● Due to spread of primary TB infection from elsewhere in the body to lung apex via bloodstream. 
● Simon focus nodules are often calcified.
■ ASSMAN FOCUS:-
**********************
●infraclavicular lesion of chronic pulmonary T.B.
● Lymph node involvement is RARE.
secondary TB more likely to cavitate than primary TB. 
●Endobronchial spread along nearby airways is relatively common finding, resulting in relatively well-
defined 2-4 mm nodules or branching lesions TREE-IN-BUD APPEARANCE on CT scan.
#tuberculoma formation and miliary TB are also recognised patterns of secondary TB.
c) MILIARY PULMONARY TUBERCULOSIS
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
●Miliary tuberculosis is uncommon but carries a poor prognosis.
● It represents haematogeneous dissemination of an uncontrolled tuberculous infection.
● seen both in primary and post-primary tuberculosis. 
● lungs are usually the easiest location to image.
● Miliary deposits appear as 1-3 mm diameter nodules.
■ RICH FOCUS :-
*******************
● It is a tuberculous granuloma occurring on brain cortex that ruptures into subarachnoid space, causing
tuberculous meningitis.
■WEIGERT’S FOCUS :-
*************************
● Subintimal foci in pulmonary vein. ( d/t metastatic caseous TB.)
■ SIMMOND’S FOCUS:-
**********************
● Localized tb foci in liver.
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CONGENITAL TUBERCULOSIS:-
■■■■■■■■■■■■■■■■■■■■
● Infection with tubercle bacilli either during intrauterine life or before complete passage through birth
canal is termed as congenital tuberculosis.
● Three possible modes of infection of fetus:-
1) Hematogenous infection via umbilical vein
2) fetal aspiration of infected amniotic fluid 
3) fetal ingestion of infected amniotic fluid
● Most common "site" and most common "site of primary complex " both is --- LIVER ( primary complex
in liver is suggestive of congenital TB)
● Prognosis is poor.
● Revised criteria for diagnosis of congenital tuberculosis ( by Cantwell ) :-
******************************************
● Proven tuberculosis lesions in the infant plus one of the following:-
i. Lesions occurring in the first week of life.
ii. A primary hepatic complex
iii. Maternal genital tract or placental tuberculosis, and
iv. Exclusion of postnatal transmission by thorough investigation of contacts.
NOTE:-
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SIMON focus should be considered as secondary TB..(Pease correct this in my book #Concepts in
Pathology)
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