Surgical Pathology

GANGRENE, NECROSIS, APOPTOSIS:

A worker who is a smoker presents with a gangrene in the toe.

  1. Define Gangrene.
    —Gangrene (or gangrenous necrosis) is defined as the death/necrosis of body tissue caused by either a critically insufficient blood supply or, a serious bacterial infection.
    —It commonly affects the extremities including toes, fingers & limbs but it can also occur in muscles & internal organs.
  2. Types of Gangrene?
    —There are two types of gangrene- Dry gangrene & Wet Gangrene. A third type- Gas gangrene is a variant of Wet gangrene.
  3. Dry Gangrene:
    • Causes–
      —Arterial Blood vessel disease e.g. Arteriosclerosis, Buerger’s disease(Thrombangitis obliterans), Ranaud’s disease,
      —Trauma,
      —Ergot poisoning &
      —Diabetes mellitus.
    • Dry & shriveled skin with colour from brown to purplish blue or black. (Hb released from haemolysed RBC reacts with hydrogen sulfide- H2S, produced by bacteria resulting into the formation of black colured iron-sulfide).
    • Dry gangrene is histologically coagulation necrosis without liquefaction.
  4. Wet Gangrene:
    • The gangrene is considered wet if there is bacterial infection in the affected tissue which has lead to the gangrene.
    • The affected part is stuffed with blood favouring the rapid growth of putrefactive bacteria.
    • The toxins produced by bacteria are absorbed & reached the systemic circulation causing septicaemia & septic shock which can be fatal.
    • The spreading wet gangrene has no clear-cut line of demarcation.
    • Examples of wet gangrene:
      —gangrene of bowel (strangulated hernia, volvulus, intussusception)- due to decreased venous return; the affected part is swollen, soft, putrid, rotten & dark.
      —Diabetic foot- wet gangrene due to high glucose in the necrosed tissue favours growth of bacteria.
      —Bed sore- in bed-ridden patient, over sacrum, buttocks etc.
  5. Gas Gangrene:
    • A type of wet gangrene caused by infection with Clostridium perfringens (& others), which produces toxins causing gas formation in the tissue.
    • Usually affects deep muscular tissue; the affected part is swollen, oedematous, painful, & crepitant (the crepitus is due to accumulation of gas within the tissue).
    • HIstologically
      —it is coagulative necrosis with liquefaction of muscle fibres,
      —presence of large no. of Gram+ve bacilli
      —in the peripheral area- leukocyte infiltration, oedema, & congestion.
  6. Causes & pathophysiology of gangrene?
  7. Treatment options?
  8. Difference between Dry & Wet gangrene:
FeaturesDry gangreneWet gangrene
1. SiteUsually limbsMost common in bowels
2. MechanismArterial occlusionMainly venous obstruction,
less commonly arterial occlusion
3. MacroscopyDry, shrunken, BlackMoist, soft, swollen, rotten, dark
4. PutrefactionLimited due to poor blood supplyMarked due to stuffing of organ with blood
5. Line of DemarcationPresent at the junction of healthy & gangrenous partNo clear line of demarcation
6. BacteriaBacteria fail to surviveNumerous bacteria present
7. PrognosisBetter as little or, no septicaemiaPoor due to profound septicaemia
Difference between Dry & Wet gangrene

Necrosis & Apoptosis

  1. Define Necrosis.
    —Necrosis is a form of cell death in which there is damage to the cellular membranes & loss of ion homeostasis causing cellular enzymes to leak out & ultimately digestion the cell.
    —A premature death of cells in living tissue resulting from cell injury; the cell dies due to autolysis cellular enzymes & loss of ion homeostasis.
  2. Types of cell death?
    —Necrosis & Apoptosis.
  3. Pathogenesis of Necrosis?
    —Necrosis is the culmination of irreversible cell injury.
    —Severe/prolonged ischemia⇒ reduced O2 supply/mitochondrial swelling & damage⇒ failure of energy production (ATP generation) ⇒ damage to cellular membranes (plasma membrane & lysosomal membranes) ⇒leakage of cellular contents (enzymes etc.) ⇒irreversible damage to cellular lipids/proteins/nucleic acids (by free radical- reactive oxygen species (ROS); and others
  4. Types/Classification of Necrosis?
    • Coagulative Necrosis–
      —preservation of underlying tissue architecture for several days after cells-death,
      —firm texture
      —characteristic of infarcts (areas of necrosis by ischemia) in all solid organs supplied by end arteries except brain.
    • Liquefactive Necrosis–
      —in suppurative focal bacterial &, occasionally, fungal infections {microbes stimulate rapid accumulation of inflammatory cells, & the enzymes of leukocytes digest (“liquefy”) the tissue}.
      —hypoxic/ischemic death of cells within the CNS/brain.
      —the dead cells are completely digested, transforming the tissue into a viscous liquid, eventually removed by phagocytes.
      —In a bacterial infection, the material is frequently creamy yellow-pus. 
    • Caseous Necrosis–
      —in granulomatous inflammation, e.g. TB
      —grossly, “cheese-like”(caseous), friable, yellow-white  appearance of the area of necrosis
      —architecture completely obliterated, cellular outlines destroyed
      —Necrotic tissue is surrounded by macrophages & inflammatory cells- called Granuloma (a nodular inflammatory lesion).
    • Fat Necrosis–
      —focal area of fat destruction
      —traumatic
      —Enzymatic- e.g. in Acute Pancreatitis {the release of activated pancreatic lipases into pancreatic substance & peritoneal cavity- liquefaction of fat cells membrane, splitting of triglycerides within fat cells- release of fatty acids which combine with calcium (Fat saponification) to form chalky white areas }.
    • Fibrinoid Necrosis–
      —a special form of necrosis seen in immunologically mediated diseases, e.g. Polyarteritis nodosa
      —complexes of Ag-Ab are deposited in the wall of blood vessels, which along with plasma proteins leak into the damaged vessel-wall forming bright pink, amorphous “Fibrinoid” (fibrin-like).
      —also seen in severe HTN.
  5. What is Apoptosis?
  6. Difference between Necrosis & Apoptosis?

TB/Lymphoma

Stem : 24 year old young lady came back from Bangladesh recently came to out-patient with complain of a neck lump along with
night sweats, low mood, depression & lack of appetite. Considering this as pathology station answer the following questions.

Q1. What is the diagnosis/differential diagnosis ? TB and lymphoma( NHL)

Q2. What is the histological appearance of TB? Caseous necrosis n granuloma,
langhans type giant cells., AFB

Q3. What are the tests for TB – culture, stain (Ziel-Neelson), sputum examination ,Mantoux
test, PCR to differntiate mycobacteria t.b from other species , Quantiferon (
interferon gamma release assays= IGRA ), FNAC of lymph node.

Q4. For Investigations where wil you send the sputum to? (he didn’t want to
hear all that rubbish about ZN stain, auromine rhoamine gel. He wanted to
hear, microbiology lab, cytology lab.)

Q5.What are the other investigations ? (TB PCR, mantoux, IF- gamma, AFB .)

Q6. What is Granuloma? –focal area of chronic inflammation –aggregate of epithlioid
histiocytes (arranged in clusters,little phagocytic activity, produce ACE e.g.
Sarcoidosis

Q7. Types/Classification of Granuloma?
Infection: Tb ,leprosy,syphilis,actinomycosis
Inflammation: sarcoidosis, crohn,PBC, Wegner granulomatosis
Foreign body :beryllium, silica, sutures, talc,
Malignancy : Hodgkin ds

Q8. What is Giant cell of Langerhans? Epitheoid cell, Horseshoe arrangements of
peripheral nucleus at one pole.e.g.TB

Q9.How will do Rapid detection of Mycobacterium ? Recombinase polymerase
amplification (RPA)

Q10. FNAC result shows necrotic tissue, histiocytes, giant cells, what is the diagnosis ? TB

Q11. What are giant cells ? multinucleated cells comprising of macrophages
converted epitheloid cells. Types : histiocytic,langhans,foreignbody,Touton.

Q12. How long does a TB culture take? 18-24 days , 4-6 weeks

Q13. What is the proteinaceous substance that can be found systemically
in TB ? AA amyloid

Q14. What will you do once you collected the sputum sample? (Put in
biohazard bag, inform CDC, microbiology dept, . I wasn’t sure about the UK
equivalent, so I said I will inform the UK equilvalent of CDC and ministry of
health. He laughed really loudly and asked how do we do it in Singapore. I
said online or call)

Q15. What other mycobacterium do you know? Mycobacterium avium
intercellulare, M. ulcerans, M. kansaii

Q16 What is Mycobacterium? Obligatory aerobic ,Non sporulating,nonmotile, weakly
G+ rod( order : actinomycetales)

Q17. How will you label the sputum specimens? Biological Substance Category B –
( highly infectious – red) , diamond mark which is UN3373

Q18. Where wil you put the specimen? in a biohazard bag

Q19. What are the culture media for mycobactetia?
Solid : lowenstein jensen media, middle brooke media and Ogawa
Liquid: BACTEC/MGIT ( mycobacteria growth indicator tube)

Q20. What are the Public health concern/ community concerns?
1. notify the consultant in communicable disease control (CCDC)
2. Avoid work in food factory
3. Use mask during sneezing or coughing
4. takes DOTS ATT,
5. isolation

Q21. What is Contact tracing ? Identification & diagnosis of persons who may have
come into contact with an infected person in last 21 days.

Q22. What is your advice to contacts ? councelling,screening & treatment
of other family members

TESTICULAR TUMOUR

Testicular tumour

Stem: A 35 year old male presents to surgical out-door with the complain of right sided inguinal mass for one month. On examination he has single palpable testis. He is otherwise healthy. Consider this surgical pathology station & answer the following questions.

  • Q. What is your differential diagnosis?
    A–  —UDT,
    — Malignancy of testis e.g. seminoma, teratoma etc,
    — Inguinal hernia
    — Varicocoele,
    — Inguinal lymph node enlargement (due to primary or secondary cause)
  • Q. 3 Possibilities of a testicular mass? (? in scrotum)
    —Tumour
    —Varicocele
    —Spermatocele
    —Hydrocele
    —Inguinal Henia
  • Q. Why do you think this will be testicular tumour/Ca ?
  • Q. Types/Classification of testicular tumour?
  • Q. If this patient would be a 60 year old male, what would be the most common type of testicular tumour in this patient?
    A-     Lymphoma.
  • Q. How would you proceed to reach a diagnosis?
    A– To start with I will take history from the patient & followed by clinical examination. I will proceed further by advising USG & blood investigations for tumour markers (β-hcg, α-fetoprotein, LDH).
  • Q. What would you expect to find on Ultrasound?
    A– USG will show consistency of the maas/lesion (solid or cystic), tissues of different origin like from ectoderm, mesoderm or endoderm e.g. in teratoma & information about lymphovascular invasion.
  • Q. USG shows UDT with solid & cystic components & pathology report is given. Give your comment.
    A-     Teratoma, positive margin, & Lymphovascular invasion; stage- T4,Nx,Mx.
  • Q. Now, as histopathology confirms testicular carcinoma, what will you do next?
    A-    Staging of the disease with CT-TAP (CT  scan of Thorax, Abdomen & Pelvis).
  • Q. CT-TAP shows RPLN (retroperitoneal lymph node) compressing on IVC (inferior vena cava). How will this lead to thrombosis?
    A-     Virchow’s triad: stasis, hypercoagulability, endothelial injury
  • Q. Describe lymph drainage of testes.
  • Q. Enumerate Etiology/Causes of Cryptorchidism?
    A-
  • Q- Difference between UDT & Ecopic testis?
    A-
  • Q- How would you treat this patient?
    A- Diagnosis, staging, Discuss with MDT-multidisciplinary team, with the pt & pt-carer

For the …

  • Q- What are the markers would you ask for?
    A-
  • Q. In which type of tumour these markers will be raised?
    A-
  • Q. Where is βHCG normally produced?
  • Q. What is choriocarcinoma?
  • Q. Now, imagine the patient has been operated & he developed haematoma. Describe the stages of haematoma resolution?

A-

  • Q. After few months the pt develops small pneumothorax, what would you think of diagnosis/ how would you interpret this situation?
    A- It could be due to metastasis to lungs for which I will advise CT scan chest
  • Q. Define Metastasis?
    A-
  • Q. What is the cell of origin of seminoma?
    A-
  • Q. Histopathology shows papillary thyroid tissue & GIT adenocarcinoma. Why?
  • Q. Can you describe the testicular tumour classification…?
    A
  • Q. Given a pathology report post orchidectomy- CD4 & CD20 (can’t remember) positive & other features on the report pointed towards lymphoma. What is it?
    A-
  • Q. Other sites of lymphoma?
    A-
  • Q. Risk factors for lymphoma?
    A-

TB/Lymphoma

Stem : 24 year old young lady came back from Bangladesh recently came to out-patient with complain of a neck lump along with
night sweats, low mood, depression & lack of appetite. Considering this as pathology station answer the following questions.

  • Q1. What is the diagnosis/differential diagnosis ? TB and lymphoma( NHL)
  • Q2. What is the histological appearance of TB? Caseous necrosis n granuloma, langhans type giant cells., AFB
  • Q3. What are the tests for TB – culture, stain (Ziel-Neelson), sputum examination ,Mantoux test, PCR to differntiate mycobacteria t.b from other species , Quantiferon (interferon gamma release assays= IGRA ), FNAC of lymph node.
  • Q4. For Investigations where wil you send the sputum to? (microbiology lab, cytology lab.)
  • Q5.What are the other investigations ? (TB PCR, mantoux, IF- gamma, AFB .)
  • Q6. What is Granuloma? –focal area of chronic inflammation –aggregate of epithlioid histiocytes (arranged in clusters,little phagocytic activity, produce ACE e.g. Sarcoidosis
  • Q7. Types/Classification of Granuloma?
    Infection: Tb ,leprosy,syphilis,actinomycosis
    Inflammation: sarcoidosis, crohn,PBC, Wegner granulomatosis
    Foreign body :beryllium, silica, sutures, talc,
    Malignancy : Hodgkin ds
  • Q8. What is Giant cell of Langerhans? Epitheoid cell, Horseshoe arrangements of peripheral nucleus at one pole.e.g.TB
  • Q9.How will do Rapid detection of Mycobacterium ? Recombinase polymerase amplification (RPA)
  • Q10. FNAC result shows necrotic tissue, histiocytes, giant cells, what is the diagnosis ? TB
  • Q11. What are giant cells ? multinucleated cells comprising of macrophages converted epitheloid cells. Types : histiocytic,langhans,foreignbody,Touton.
  • Q12. How long does a TB culture take? 18-24 days , 4-6 weeks
  • Q13. What is the proteinaceous substance that can be found systemically in TB ? AA amyloid
  • Q14. What will you do once you collected the sputum sample? (Put in biohazard bag, inform CDC, microbiology dept, . I wasn’t sure about the UK equivalent, so I said I will inform the UK equilvalent of CDC and ministry of health. He laughed really loudly and asked how do we do it in Singapore. I said online or call)
  • Q15. What other mycobacterium do you know? Mycobacterium avium intercellulare, M. ulcerans, M. kansaii
  • Q16 What is Mycobacterium? Obligatory aerobic ,Non sporulating,nonmotile, weakly G+ rod( order : actinomycetales)
  • Q17. How will you label the sputum specimens? Biological Substance Category B – ( highly infectious – red) , diamond mark which is UN3373
  • Q18. Where wil you put the specimen? in a biohazard bag
  • Q19. What are the culture media for mycobactetia?
    Solid : lowenstein jensen media, middle brooke media and Ogawa
    Liquid: BACTEC/MGIT ( mycobacteria growth indicator tube)
  • Q20. What are the Public health concern/ community concerns?
    1. notify the consultant in communicable disease control (CCDC)
    2. Avoid work in food factory
    3. Use mask during sneezing or coughing
    4. takes DOTS ATT,
    5. isolation

  • Q21. What is Contact tracing ? Identification & diagnosis of persons who may have come into contact with an infected person in last 21 days.
  • Q22. What is your advice to contacts ? councelling,screening & treatment of other family members