1 Introduction
2 Tissue processing and histopathology review
Origin | Recommended Immunostains | Comments |
---|---|---|
Colorectal | CK7-/CK20 + in combination with CDX2 + is highly suggestive of colorectal origin | |
Pancreaticobiliary and upper GI | Pancreas: CK7 + /CK20- (majority) [8] Biliary: CK7 + /CK20 + (majority) [9] Gastric: CK7 + /CK20- (majority) CDX2-/weak + , CK19 + , AE1/3 + , Hep Par-1- | CK7 + /CK20- in combination with CDX2- /weak + is suggestive of upper GI/pancreaticobiliary origin, however does not outrule primary lung origin Note: Gata3 + pancreatic adenocarcinoma (16%) [10] |
Liver | Hep-par1 can be lost in poorly differentiated hepatocellular carcinoma [13] Note: CK7 + in fibrolamellar carcinoma [14] | |
Lung | Adenocarcinoma: TTF-1 (80%), Napsin A (80%), [11] CK7 + /CK20- | TTF-1 staining trumps all other stains and is highly suggestive of lung adenocarcinoma origin [18] Note: CK7 + /CK20 + lung mucinous adenocarcinoma (17%) [19] |
Breast | Gata3 + (> 90%) [17], CK7 + /CK20- (> 90%), | Note: mammaglobin + in mammary analogue secretory carcinoma of salivary gland |
Prostate | PSA can be lost in high grade adenocarcinoma [24] NKX3.1 has a high sensitivity and specificity but can be positive in male breast cancers [22] | |
Gynae tract | High grade serous: P53 -/ + (mutant pattern), p16 diffuse + , ER ± , Pax8 + Endometrioid: p53 wild type pattern, p16-, Pax8 + , ER + (> 90%) [11] Cervical adenocarcinoma: ER-, Pax8 + (70%) [25], HPV ish + , p16 diffuse + | CK7 + /CK20- in combination with Pax8 + is highly suggestive of gynae tract origin Note: CK7 + /CK20 + in primary mucinous tumours of ovary (74%) [26] |
Urothelial | p63 is not specific for urothelium and is positive in squamous tumours from other sites | |
Neuroendocrine carcinomas (NEC) | Chromogranin A ± , CD56 + , synaptophysin + , AE1/3 + , SSTR2A ± Cytokeratin weak ± | While chromogranin A is most specific, poorly differentiated NECs are often negative [29] Synaptophysin is very sensitive but less specific [29] however is useful when Chromogranin A - While TTF-1 + in a well-differentiated NET favours primary site from lung/head and neck, less helpful in NECs as may express it regardless of primary site |
Renal | RCC + , PAX8 + , 56CD10 + , CK7 ± , CK20-, AE1/3 + | CK7 + in papillary RCC type 1, clear cell papillary RCC and CK7- in clear cell RCC, papillary RCC type 2 [30] |
Thyroid | CK7 + /CK20-, CK19 + | Medullary thyroid carcinoma shows a different profile: TTF-1 + , thyroglobulin-, Pax8 + , calcitonin + , chromogranin + , synaptophysin + [33] |
Adrenal cortex | ||
Germ cell tumour | OCT3/4 + , SALL4 + , PLAP + , HCG + , AFP + , glypican3 + , CK7-/CK20- [23] | |
Mesothelioma |
Favourable subsets | Unfavourable subsets |
---|---|
Adenocarcinoma with colonic profile (CK20 + , CK7-, CDX2 +) | Poorly differentiated carcinoma |
Women with papillary adenocarcinoma of the peritoneal cavity | Adenocarcinoma metastatic to liver or other organs |
Women with adenocarcinoma involving axillary lymph nodes | Non-papillary malignant ascites (adenocarcinoma) |
Squamous cell carcinoma involving cervical lymph nodes | Multiple cerebral metastases (adenocarcinoma or squamous cell carcinoma) |
Squamous cell carcinoma involving only inguinal lymph nodes | Multiple lung or pleural metastases (adenocarcinoma) |
Poorly differentiated neuroendocrine carcinomas | Multiple metastatic bone disease (adenocarcinoma) |
Men with blastic bone metastases and raised prostate specific antigen (PSA) | Squamous cell carcinoma of the abdominal cavity |
Patients with a single small and potentially resectable tumour |