Etiology of Neoplasia😊

Etiology of Neoplasia

1. Radiation:

Ultraviolet (UV) Radiation:

UV B is most carcinogenic ("bad one") → skin cancers.

Ionizing Radiation:

Most common cancer:

Acute Myeloid Leukemia (AML).

Most common thyroid cancer:

Papillary Carcinoma Thyroid.

Cancer NEVER associated:

Chronic Lymphocytic Leukemia (CLL).
Mnemonic: No oncall (CLL) radiologist (Radiation)

2. Chemicals:

Alcohol → Hepatocellular Carcinoma.

Tobacco → Oral cancer, Lung cancer, Renal Cell Carcinoma.

Asbestos:

Most common carcinoma:

Adenocarcinoma Lung.

Most specific tumor:

Mesothelioma Lung.

DES (Diethylstilbestrol)

Clear cell tumors of cervix, vagina in daughters

("DES daughters").

Estrogen

Endometrial Carcinoma.

OCP (Oral Contraceptive Pills)

Cervical Cancer.

OCP protects against ovarian cancer

VAT Chemicals (Vinyl Chloride, Arsenic, Thorotrast):

Sources:

Polyvinyl chloride (plastics)
Pesticides (Arsenic)
Thorium & contrast dye (radiology).

Result in Angiosarcoma of the Liver.

Mnemonic: VAT of the liver

Ames Test:

Determines mutagenic potential of a chemical.

Mnemonic: Amen paranjapo Mutant ayi

Benzene vs. Benzidine:

Benzene → AML

Benze → Amal (AML) chora niirakki benze vaangi (blood cancer)

Benzidine → Urinary bladder cancer

Benze Idich → UB potti

3. Microorganisms:

Bacteria:

Helicobacter pylori (H. pylori):

Catalase, oxidase, urease positive.

COU positive

Diseases caused:

Gastritis.
Peptic Ulcer disease.
Attributed to cag A and vac A.

Maltoma of stomach
Adenocarcinoma Stomach

Stains used:

Warthin-Starry Silver (black),
Modified Giemsa (blue).

CLO Test

Fungus:

Aflatoxin

from Aspergillus flavus

Source: Peanut/groundnut contaminant.

Causes Hepatocellular Carcinoma (HCC).

Mechanism: P53 mutation at codon 249.

Mnemonic:

Peanut → 250Rs (249 codon) stored in a flat (Aflatoxin) → 53rd floor (P53) → turned toxic
Police came → P53 → fill in the blanks -> 249

Parasites:

Schistosoma haematobium

Squamous Cell Carcinoma of Urinary Bladder.

Mnemonic: S for S

Clonorchis sinensis

Cholangiocarcinoma.

Mnemonic: C for C

Viruses:

Human Papilloma Virus (HPV):

Associated with squamous epithelium cancers:

Cervical, Penile, Anal canal, Esophageal, Head & Neck.

Koilocytes

Modified keratinocytes

Have a pyknotic nucleus

Around nucleus, a clear space (perinuclear halo)

Features of HPV or Verruca

Kozhitharam (koilocytes) arnn → HPV vannu → Now no one around him (peri nuclear halo)

Ellarum veruthu (verucc) →

Both →

Plane face (verucca plana → on face) → Black colored (Hyperpigmeted)
Vulgar body (verucca vulgaris → anywhere in body) → ↑↑↑ skin thickness in body

HPV Proteins & Carcinogenesis:

Protein	Notes	ㅤ
L1 capsid protein	Vaccine development	L → Live vaccine
E1 & E2	Proteins needed for viral replication	2 → To Control
E2	Controller	ㅤ
E4, E5	Cell changes → koilocytes (raisin nucleus + perinuclear halo)	4, 5 Condoms
E6, E7	Carcinogenesis	ㅤ
↳ E6	inactivates p53 (policeman)	6 → 5 → 3; P ⇔ 6
↳ E7	inactivates RB (governor gene)	Seven → S → SRB → RB

Epstein-Barr Virus (EBV):

Primary disease: Infectious Mononucleosis

Also called Glandular Fever or Kissing Disease

Ballerina () + Paul

Ballerina
Naughty → NAHT

says 21 (CD21) yr → actually 18 (8 T cell)

Kissed → EBV
Down there → Downey, Duncan
Hairy → Hairy cell leukemia
then abdomen (Gastric cancer > Nasopha)
then neck (Nasopha)

Pathogenesis

Polyclonal B cell activation

Entry: via CD21/Cr2 receptor

Molecules:

LMP 1
EBNA 2 (activates SRC proto-oncogenes)
vIL10 (anti-inflammatory)

Skin manifestation:

Patients present with fever, lymphadenopathy, sore throat

misdiagnosed as bacterial
Given antibiotics (usually Amoxicillin or Ampicillin)

Develop an exanthem on body called Ampicillin rash

Mnemonic: Kiss cheythapo hairl ayipoi

Malignancies

Carcinomas:

M/c: Gastric carcinoma
Nasopharyngeal carcinoma

Lymphomas:

Hodgkin’s (mixed cellularity)
Non-Hodgkin: Burkitt’s, DLBCL, Post-transplant lymphoma

Sarcomas: Leiomyosarcoma

Other conditions

Duncan Syndrome (lymphoproliferative syndrome)

Hairy cell / Oral leukoplakia

Lab Diagnosis

Microscopy:

Atypical lymphocytes (Downey cells)

= CD8 T lymphocytes (Cytotoxic T cells)

"Ballerina skirt appearance"

Heterophile antibody detection:

Paul Bunnell Test (older)
Monospot Test (newer)

Specific Antibody Tests:

Viral capsid antigen
Early antigen
EBNA

Most sensitive & specific:

Nucleic Acid Hybridisation Test

Treatment

Acyclovir

Rituximab

HTLV (Human T-cell Leukemia Lymphoma Virus):

Retrovirus

Involves TAX gene.

Transmission: Blood, body fluids, breast milk

Diseases:

Tropical Spastic paralysis
Causes Adult T-cell Leukemia Lymphoma (ATLL)

(T-cell leukaemia/lymphomas).

Microscopy: Clover leaf cells (flower-like nucleus).

Mnemonic:

HTLV → Hotel → we give flower (Flower like nucleus) and cards (Clover leaf)
Hotel should pay tax
Tax adachillel Paralysis

HHV-8 (Human Herpes Virus 8):

Kaposi Sarcoma (vascular tumor)

Association: Seen in HIV-positive individuals

Gamma virus

Most Common Sites:

First:

Seen on legs
Presents with deep red to bluish papules and nodules

Second: Lymph node.

M/c lid malignancy in HIV

Microscopy:

Shows spindle cells.

IHC (Immunohistochemistry):

LANA (latency associated nucleic acid) positive.

Kakkusil pokumbo sing LALA (LANA) and SPIN (Spindle)

Primary Effusion Lymphoma

Effusions (pleural, pericardial)

CD30 & CD38 +ve

CASTLEMAN Disease

Site: lymph nodes

Symptoms: B cell symptoms (fever, night sweats, weight loss)

Histology:

"Onion skinning of lymphocytes"
"Lollipop follicles"

A patient presents with abdominal distention and intermittent fever. Peripheral smear findings are normal. A tumor is resected and the histopathology image of the resected lymph node is shown below. What is the most probable diagnosis ?

A. Angiolymphoma
B. Hodgkin’s lymphoma
C. IgG-4 related disease
D. Castleman disease

ANS

Castleman disease