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1. GASTROPATHOMEET CASE –1 PRESENTER – DR.ROUSHNI KUMARI(S.R) MODERTOR- DR.ZEENAT S IMAM(ASSISTANT PROFESSOR)

2. 45 years , Female OPD/Registration no. – 108112300241891 Lab no.S-23-8582

3. Gross Specimen – Container i) labelled an Right sided Hemicolectomy specimen Container ii)Unlabelled

4. Container I) labelled an Right sided Hemicolectomy specimen Received right sided hemicolectomy specimen comprising part of terminal ileum measuring 10.cm in length, Caecum measuring 4.5cm in length. Ascending colon measuring 16cm in length, Proximal resection margin measuring 1.8cm in diameter Distal resection margin measuring 2.5cm in diameter. Attached appendix measuring 3. 5cm in length and 0.5 cm in diameter External surface.of terminal ileum is unremarkable.Cut surface - Normal mucosal fold seen External surface of caecum and colon – congested Cut surface A grey white ulceroproliferative tumour in seen in ascending colon measuring 8.5x4.3x2.7cm . It is involving the bowel wall circumferentially. Tumour is solid and firm in inconsistency showing focal areas of haemorrhage . Tumour is 15cm from proximal resection margin & 8.5 cm from distal resection margin Grossly the tumor reaches upto the serosa (0.1cm away). Appendix External surface - focal area of congestion seen Cut surface lumen seen.

5. Lymphnodes At the level of tumor, 17 lymph nodes isolated, largest measuring 1.5x1x0.5 cm. Below the level of tumor, 16 lymph nodes isolated, largest measuring 1x0.5x0.5cm. Above the level of tumour , 10 lymph nodes isolated. largest measuring 1x0.5x0.5cm. Container ii)Unlabelled Received grey white soft tissue piece measuring 1x0.5x0.5cm. 3lymphodes isolated, largest measuring 0.5x0.5x0.2cm.

6. GROSS

7. MICROSCOPY&IMPRESSION Container 1 labelled as Right extended hemicolectomy Procedure Right extended hemicolectomy Tumour site -Ascending colon Specimen integrity - Intact Macroscopic tumour perforation - Not identified Histologic Type - Carcinoma Differenitial include i ) Poorly Differentiated Adenocarcinoma ii)Large Cell Neuroendocrine Carcinoma Tumour extension - Tumour invades muscularis propria Margins -Proximal resection margin free of tumour Distal resection margin - free at tumour Lymphovascular invasion Not identified Perineural invasion Not identified

8. Lymph nodes at the level of the tumour , 0/17 (17 lymph nodes isolated , all showing reactive changes) Lymph nodes below the level of the tumour . 0/16 (16 lymph nodes isolated, all showing reactive changes) Lymph nodes above level of the tumour , 0/10 (10 lymph nodes isolated, all showing reactive changes) Appendix Unremarkable and free of tumour Container 2) Unlabelled Lymph node 0/3 (3 lymph nodes isolated, all showing features of reactive hyperplasia)

9. Immunohistochemistry CD X2 - Diffuse positive Synaptophysin : Focal and patchy positive NSE-Strong and diffuse positive CD 56 Negative CK 20-Negative LCA –Negative CD117 Negative Ki-67-70% Based on the IHC findings. diagnosis of Large Cell Neuroendoerine Carcinoma is favoured over Poorly Differentiated Adenocarcinoma subject to the positivity of IHC marker Chromogranin ADVICE IHC with Chromogranin is mandatory for confirmation of diagnosis.

10. CD X2 - Positive

11. NSE - Positive

12. Ki67 – 70%

13. Ck20 –Negative

14. CD 56 - Negative

15. Synaptophysin – Negative

16. LCA - Negative

17. CD 117 - Negative

18. CD X2 – Positive CEA – Negative Calretinin – Negative Ki67 – 60%

19. Pan CK – positive Synaptophysin – negative Chromogranin A – negative CD 56 – Negative CK 7 – Negative CK 20 - Negative

20. Discussion 1. Poorly Differentiated Adenocarcinoma 2. Large cell Neuroendocrine carcinoma of colon 3. Medullary carcinoma of colon

21. Poorly Differentiated Adenocarcinoma 15 – 20% of adenocarcinoma , Mean age – 60 -70 years, M=F

22. Positive stains cK20 CDX2  Negative stains CK7 , except in rectal adenocarcinomas

23. Large cell Neuroendocrine carcinoma Epidemiology – rare, 0.25% of colorectal carcinoma Age – mean age – 60 years Site – Caecum or right colon Microscopic ( histologic ) description An organoid structure with prevalent large trabeculae , rosette-like and palisading patterns, and solid nests with central necrosis, sometimes with single-cell necrosis and thick stroma . NEC cells display severe atypia , brisk mitotic activity (often with atypical mitoses. Large cells (~3x size of small cell carcinoma) with abundant amphophilic cytoplasm, intercellular membranes, nuclear pleomorphism , variably coarse, granular or vesicular chromatin with prominent nucleoli  IHC - Neuroendocrine markers, usually at least 2 diffuse and strong ( chromogranin ,  synaptophysin , CD56)

24. Medullary carcinoma of colon Epidemiology – 5-8 cases for every 10,000 colorectal carcinoma. Annual incidence – 3.47 per 10 million population. 7th decade F>M Site – caecum and proximal colon Subtype of poorly differentiated colon adenocarcinoma Sheets of malignant cells with vesicular nuclei, prominent nucleoli, and abundant eosinopnilic cytoplasm, exhibiting prominent infiltration by lymphocytes . Aberrant immunohistochemical pattern. with loss of CDX2 and CK20 Neuroendocrine markers (MLH1 and MSH2) are negative on IHC. Positive stains – Calretinine , MUC-1, MUC-2 and TFF-3.

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