Adenocarcinoma

Definition

Adenocarcinoma is a malignant epithelial tumour showing glandular differentiation. Histologically it features irregular malignant glandular structures lined by pleomorphic columnar cells, abundant intraluminal mucin, infiltration through the muscularis mucosae, desmoplastic stromal reaction, and lymphovascular invasion.

General / Essential Features

• Irregular, atypical glandular structures — architectural distortion
• Abundant intraluminal mucin (mucinous variant: >50% mucin pools)
• Cancer cells infiltrating through the muscularis mucosae into submucosa
• Lymphocytic and plasma cell infiltration in the stroma
• Desmoplastic stromal reaction around tumour glands
• Metastasis to regional lymph nodes and distant organs

Sites

• Colorectum: most common adenocarcinoma site in Western countries
• Stomach: intestinal type (H. pylori–driven) and diffuse type (signet-ring cells)
• Lung: peripheral, arising from pneumocytes — most common lung cancer type
• Pancreas: ductal adenocarcinoma — head of pancreas (75%)
• Breast: invasive ductal carcinoma — most common breast malignancy
• Prostate, endometrium, ovary, cervix (endocervical type)

Pathophysiology

Adenocarcinoma follows the adenoma–carcinoma sequence (colon) or Barrett's metaplasia–dysplasia–adenocarcinoma sequence (oesophagus). Driver mutations include KRAS, TP53, SMAD4 (colon); CDH1, RUNX3 (gastric); EGFR, ALK, ROS1 (lung). Invasion is mediated by MMPs and E-cadherin loss (epithelial–mesenchymal transition).

Etiology

• Colonic: adenoma–carcinoma sequence; HNPCC (Lynch syndrome), FAP
• Gastric: H. pylori → chronic gastritis → intestinal metaplasia → carcinoma
• Lung: smoking (though adenocarcinoma is the commonest type in non-smokers)
• Pancreatic: smoking, chronic pancreatitis, hereditary pancreatitis

Clinical Features

• Colorectal: change in bowel habit, rectal bleeding, weight loss, mass per rectum
• Gastric: dysphagia, weight loss, early satiety, Virchow's node
• Lung: haemoptysis, pleural effusion, clubbing
• Pancreatic: painless obstructive jaundice, Courvoisier's sign, steatorrhoea

Diagnosis

• Endoscopy and biopsy: colonoscopy for colorectal, OGD for gastric
• CT/PET-CT: staging and metastasis assessment
• Histopathology: glandular architecture, invasion, desmoplasia
• Molecular profiling: KRAS, EGFR, ALK, HER2, MSI/MMR status

Treatment

• Surgical resection: hemicolectomy, gastrectomy, pneumonectomy, Whipple's
• Adjuvant chemotherapy: FOLFOX (colorectal), FLOT (gastric), carboplatin-paclitaxel (lung)
• Targeted therapy: bevacizumab (anti-VEGF), cetuximab (anti-EGFR), osimertinib (EGFR-mutant lung)
• Immunotherapy: pembrolizumab for MSI-high or PD-L1 positive tumours