Pathology case presentation with discussion, squamous cell carcinoma, grossly and histology with IHC markers differentiation of different types of non small cell carcinoma .

1. PATHOLOGY CONFERENCE
SUPERVISOR:
Dr. KUMUD GUPTA,
HOD, DEPARTMENT OF PATHOLOGY, NITRD
DR. SANKAR K
SR, Department of Pathology, NITRD
PRESENTED BY:
Dr. Ambika Prasad Gupta,
Junior Resident, NITRD

2. CHIEF COMPLAINTS
• 69 year, male, labour by occupation, presented with the
complaints of –
– right sided chest pain : 3 months
– loss of appetite and weight loss : 2 months
– cough with mucoid expectoration : 1 month
– breathlessness : 1month

3. History of present illness-
Chest pain:
• Right sided
• 3 Months
• Gradual in onset
• Diffuse
• Dull aching
• Radiating to back
• Pain increased during exertion
• No relief with NSAIDs

4. History of present illness-
Breathlessness :
• Insidious onset
• Gradually progressed from MMRC grade 1 to MMRC
grade 4 over 1 month
• Aggravated on supine and Left lateral decubitus
position
• No diurnal variation
• No h/o of orthopnea or PND

5. History of present illness
Cough with expectoration:
• About 50ml per day
• Mucoid
• not foul smelling
• not associated with hemoptysis
• no diurnal and postural variations
• cough increased on left lateral decubitus

6. History of present illness
H/o loss of appetite present
Weight loss about 8 kg in last 2 months
Negative history-
No h/o fever, hemoptysis,
No h/o any trauma to chest
No h/o contact to TB patients
No h/o of joint pain, back pain or stiffness

7. PAST HISTORY:
Not known to have diabetes, hypertension, thyroid disorder
No h/o surgery/blood transfusion/ICD insertion
No h/o previous hospitalization
No similar history in the past
Family history:
Nothing suggestive. No family history of tuberculosis, cancer.

8. PERSONAL HISTORY:
• Labour by occupation, illetrate
• Chronic smoker, 20beedi/day for 40 yrs stopped 3 month back
• Occasional consumption of alcohol for 20 yrs stopped 3 month
back
• Disturbed sleep for 1 month
• Normal bowel & bladder habits
• No relevant h/o exposure to environmental pollutants
Treatment History:
• Patient was taking CAT-I ATT for pleural effusion (on clinical
basis) since 4 weeks from private Clinic.

9. SUMMARY
69yr old male, a chronic smoker and occasional alcoholic,
labour by occupation, presented with complaints of right
sided chest pain for 3 months, cough with expectoration,
shortness of breath, loss of appetite and loss of weight since
2 months, on CAT-1 ATT since 4 weeks under private setup,
was referred to NITRD for further evaluation as patient’s
general condition was deteriorating.

10. General physical examination:
• Conscious, oriented to time, place and person
• moderately built and poor nutrition, BMI of 17.16 kg/m2
• dyspnic at rest
• using accessory muscles of respiration
• Clubbing present (grade 3)
• no pallor/icterus/cyanosis/pedal edema/palpable lymphadenopathy
• no engorgement of neck veins
• Patient prefers right lateral position in bed

11. General physical examination:
Vital signs :
• Temperature: 37.4 0C measured in left axilla (Afebrile)
• PR – 110/min, regular, normal volume and character, no radio-
radial or radio-femoral delay
• RR- 22/min, regular, thoraco-abdominal
• BP: 110/76mm of Hg, in right arm, in supine position
• Spo2 – 96%@2 lit O2/min via Nasal prong

12. SYSTEMIC EXAMINATION
Respiratory System
Upper respiratory tract : Poor oral hygiene, ENT no external abnormality seen
Lower respiratory tract
Inspection-
• Chest asymmetrical
• Trachea deviated to the left
• Chest movements reduced on Right side
• Apical impulse at 5th ICS lateral to MCL
• Intercostal spaces were full in Right hemi thorax
• No visible scars/sinus/engorged veins/swelling
• Using accessory muscles of respiration

13. SYSTEMIC EXAMINATION
Palpation:
• Findings of inspection were confirmed
• Trachea shifted to Left
• Apex beat at 5th ICS 2 cm lateral to MCL
• AP:Transverse diameter1:1.5
• Chest expansion 2.0cm
• Right hemi thorax 0.5cm, Left hemi thorax 1.5cm
• Spino-scapular distance Right 2.3cm, Left 2.1cm
• No superficial swelling/tenderness
• Tactile vocal fremitus: reduced through-out the right side

14. SYSTEMIC EXAMINATION
Percussion
• Left hemi thorax-resonant note
• Right hemi thorax – through out the right hemi thorax stony
dull note elicited
• Shifting dullness: absent
Auscultation:
• Left hemi thorax: vesicular breath sounds
– no added sounds; Vocal resonance normal.
• Right hemi thorax breath sounds were diminished
– VOCAL RESONANCE decreased through out in the right hemi thorax

15. Examination of other systems
CVS – S1 S2 heard
PA – Soft, Non-tender, No organomegaly, No free fluid, peristaltic
sound present
CNS – conscious ,oriented, GCS –normal (15/15)
No localizing signs elicited
Higher functions were WNL

16. Investigations
Hb-12.5g/dl
TLC-20,000/mm3
DLC- N-72/L-15.2/M-12.1/E-0.6/B-0.1
Pl count-2,94,000/mm3
B Sugar(R)- 125 mg/dl
B Urea-24 mg/dl
S Creatnine-0.58 mg/dl
S. Na-133 mEq/L
S. K -3.6 mEq/L
S Protein-5.55 g/dl
S. Albumin-2.72 g/dl
S. Bilirubin-0.78/0.31 g/dl
SGOT-29
SGPT-41
S Alk Phosphotase-137.35
Sputum AFB- not found
CBNAAT sputum–M Tb
not detected

17. Chest X-Ray

18. PLEURAL FLUID ANALYSIS
Protein-4.5 g/dl Sugar-84mg/dl ADA-31.3 U
CBNAAT- MTB not detected
MGIT – Negative
Cytological diagnosis- suspicious of squamous cell carcinoma.
AFB- Neg
Further workup was suggested.

21. Contrast Enhanced CT Scan CHEST (reported as)
• RIGHT side central bronchogenic carcinoma with massive
right side pleural effusion with circumferential pleural
thickening with erosions of multiple ribs.

22. Medical Thoracoscopy-
• Hemorrhagic pleural effusion was present with pleural
based multiple lesions were seen on parietal pleura and
biopsy was taken and sent for histopathological examination

23. Chest Xray (After Thoracoscopy)

24. HISTOPATHOLOGY Microscopic findings:
• Shows irregular bits of fibrous tissue infiltrated by tumor tissue
• The tumor cell are arranged in lobules and groups
• Cells are large polygonal in sheets. Cells have moderate to abundant
eosinophilic cytoplasm. Some cells shows Keratinization.
• Nuclei are variable in size and are round to elongated, few of them
have irregular nuclear border and are hyperchromatic.
• Occasional keratin pearls are also noted. Few mitosis are identified.
• Surrounding fibrous tissue shows mild mononuclear inflammatory
cell infiltrate, large area of necrosis are also noted.
• IMPRESSION-Picture is consistent with squamous cell carcinoma.

25. HISTOPATHOLOGY Microscopic findings:

26. IHC REPORT
IHC MARKER RESULT
p40 Positive
p63 Positive
TTF 1 Negative
Napsin Negative

27. SQUAMOUS CELL CARCINOMA
• Pathologically it is defined by either morphology or expression
of pneumocytic markers.
• Common- men
• Strongly correlated with cigarette smoking
• Two thirds of SCC occur centrally and frequently associated with
bronchial obstruction and post-obstructive pneumonia
• Cavitation is seen frequently.

28. Types of squamous cell carcinoma-
 Variants of squamous cell carcinoma in the 2004 World Health
Organization (WHO) classification system included-
• Papillary,
• Clear cell,
• Small cell, and
• Basaloid carcinoma
 These classification have been replaced with categories (2015,
WHO)
• Non-keratinizing
• Keratinizing
• Basaloid subtypes.

29. SQUAMOUS CELL CARCINOMA GROSS
• Commonly occur centrally (2/3rd cases)
• Involvement of main stem, lobar or segmental
bronchus is common
• Can also present as a peripheral mass
• CAVITATION is seen frequently
• SCC arise most often in segmental bronchi and
involvement of lobar and main-stem bronchus occurs
by extension
• Surrounding lung may exhibit lipid pneumonia,
bronchopneumonia, atelectasis

30. HISTOPATHOLOGY
• Characterised by presence of keratinisation and/or intercellular
bridges
• Keratinisation may take form of squamous pearls or individual cells
with markedly eosinophilic cytoplasm:
• Features prominent in well differentiated tumours, and are focally
seen in poorly differentiated cancers.
• Mitotic activity: higher in poorly differentiated tumors
• Squamous metaplasia, epithelial dysplasia and foci of frank
carcinoma in situ may be seen in bronchial epithelium adjacent to
the tumor mass

35. IMMUNO-HISTOCHEMISTRY

37. POTENTIAL TARGETABLE MUTATIONS
• FGFR1 amplification: FGFR Kinase inhibitors under study
(agent BGJ 398)
• EGFR mutation: Cetuximab along with conventional
chemotherapy
• DDR2 Mutations, and Inactivating BRAF mutations: DASATINIB
Ref: Liao RG, et al. targeted therapy for squamous cell lung cancer. Lung Cancer Manag. 2012 Dec; 1(4): 293–300.

38. POTENTIAL TARGETABLE MUTATIONS
• antibodies directed against negative co-stimulatory receptors and ligands
(CTLA-4, PD-1, PD1-L1) have demonstrated efficacy
• Immunotherapeutic approach coupled with targeted kinase inhibitors are
being tried.
• Potential targetable mutations (although present in a narrow subset of
SqCC): PDGFRA, mutations in BRAF and mutations
in JAK2, ABL1, ABL2, MET and ERBB2–4
Ref: Liao RG, et al. targeted therapy for squamous cell lung cancer. Lung Cancer Manag. 2012 Dec; 1(4): 293–300.

39. SUMMARY
• Squamous cell cancer of lung: more common in males and
smokers
• Generally centrally located, can also cause symptoms due to
obstruction
• Apart from clinical and radiological features, the mainstay of
diagnosis is histopathology and IHC. Histological features
include: keratinisation and presence of intercellular bridges
• On IHC: p40, p63 and CK5/6 positive and TTF-1, Napsin,
Mucin,CK-7, CK 20 negative.
• Immunotherapeutic approach, along with targeted kinase
inhibitors, and antibodies are being developed and few are
under trial

46. • Cytology-shows degenerating neutrophils, lymphocyte cells
with few squamous cell and smudge cells. Squamous cells are
poorly preserved, occasional squamoid cells are elongated.
Large nuclei is noted in occasional cells. Nuclear details are not
discernable. Background is dirty with with few RBCS