What are the types, pathophysiology, symptoms, and causes of carcinoma?

Carcinoma Types, Pathophysiology, Symptoms, and Causes

Carcinoma is a malignant epithelial neoplasm characterized by invasion through the basement membrane with potential for metastasis, occurring in various tissues with distinct subtypes defined by histological features, molecular alterations, and tissue of origin. 1

Types of Carcinoma

Squamous Cell Carcinoma (SCC)

• Most common histological type of penile cancer (>95%), with various subtypes classified as HPV-independent or HPV-associated 2
• Subtypes include usual, pseudohyperplastic, pseudoglandular, verrucous, cuniculatum, papillary, sarcomatoid, and mixed variants 2
• Can arise from squamous and non-squamous epithelial tissues through oncogenic transformation 3
• Represents one of the most frequent human solid tumors across multiple body sites 4

Adenocarcinoma

• Characterized by glandular or acinar differentiation, papillary structures, and cytoplasmic mucin vacuoles 2
• Histologic subtypes include acinar, papillary, micropapillary, and solid types, often with composite features 2
• Graded based on architectural and cytologic features, with acinar and papillary being low grade and solid being high grade 2
• May develop within inflammatory scars or induce stromal desmoplastic response 2

Serous Carcinoma

• Classified as low-grade or high-grade, representing different tumor types rather than variants of the same tumor 2
• High-grade serous carcinoma (HGSC) is the most common ovarian carcinoma (approximately 70%) 2
• Low-grade serous carcinoma has different pathogenesis and molecular alterations compared to HGSC 2
• May originate from fallopian tube epithelium rather than ovarian surface epithelium 5

Other Carcinoma Types

• Clear cell carcinoma: High-grade tumor with distinct morphology 2
• Endometrioid carcinoma: Graded similar to uterine endometrioid carcinomas using FIGO system 2
• Mucinous carcinoma: Infiltrating adenocarcinoma with ≥80% mucin-producing neoplastic cells 2
• Small cell carcinoma: High-grade neuroendocrine tumor with scant cytoplasm, finely granular nuclear chromatin, and absent/inconspicuous nucleoli 2
• Undifferentiated carcinoma: Shows no glandular, acinar, endocrine, or squamous differentiation 2

Pathophysiology

Carcinogenesis Process

• Begins as clonal proliferation of cells with acquired mutations 1
• Progresses to invasive carcinoma as cells breach the underlying basement membrane 1
• Invasion enables potential metastasis through blood vessels or lymphatic channels 1
• Desmoplasia (cellular fibroinflammatory response) often accompanies invasive carcinomas 2

Molecular Alterations

• Type I ovarian tumors (low-grade serous, low-grade endometrioid, clear cell, mucinous) characterized by specific mutations in KRAS, BRAF, ERBB2, CTNNB1, PTEN, PIK3CA, ARID1A, and PPP2R1A 5
• Type II ovarian tumors (high-grade serous, high-grade endometrioid, carcinosarcomas) have high frequency of TP53 mutations and BRCA alterations 5
• Small cell carcinomas exhibit immunoreactivity for keratin, epithelial membrane antigen, and thyroid transcription factor-1 2
• Squamous cell carcinomas share common genetic mutations despite arising from different body sites 4

Histologic Grading

• Well-differentiated adenocarcinomas form well-defined glands with minimal nuclear pleomorphism 2
• Moderately differentiated adenocarcinomas show disorganized growth pattern with less defined gland formation 2
• Poorly differentiated adenocarcinomas form small poorly defined glands, individual infiltrating cells, and solid areas 2
• Grading correlates with nuclear pleomorphism, mitotic activity, and atypical mitoses 2

Symptoms and Clinical Manifestations

General Symptoms

• Weight loss, debility, and systemic symptoms common in advanced disease 2
• Symptoms often depend on tumor location and extent of invasion 2

Organ-Specific Symptoms

• Lung carcinoma: Cough, dyspnea, often presenting as large hilar mass with mediastinal lymphadenopathy 2
• Penile carcinoma: Usually presents as raised or ulcerated lesions, sometimes hidden under foreskin 2
• Intestinal carcinoma: Symptoms vary based on location and extent of invasion 2

Paraneoplastic Syndromes

• Small cell lung carcinoma associated with neurologic syndromes (Lambert-Eaton myasthenic syndrome, encephalomyelitis, sensory neuropathy) 2
• Endocrine paraneoplastic syndromes due to production of polypeptide hormones (ACTH, ADH) causing Cushing syndrome and hyponatremia 2

Causes and Risk Factors

Genetic Factors

• BRCA1/2 mutations associated with high-grade serous carcinoma 2
• Lynch syndrome associated with endometrioid and clear cell carcinomas 2
• Various genetic mutations drive different carcinoma subtypes 5

Infectious Agents

• HPV infection is the main risk factor for penile cancer, with HPV 16 being the most frequent genotype 2
• Up to 50% of penile cancer cases are HPV-related 2
• HPV status may affect prognosis, with HPV-positive penile cancer potentially associated with better survival 2

Environmental and Lifestyle Factors

• Phimosis, chronic penile inflammation, lichen sclerosus, smoking, ultraviolet A phototherapy, and low socioeconomic status are risk factors for penile cancer 2
• Smoking and environmental exposures contribute to lung carcinoma development 2

Precursor Lesions

• Penile intraepithelial neoplasia (PeIN) is the precursor lesion of penile SCC 2
• Serous tubal intraepithelial carcinoma is a precursor for high-grade serous carcinoma 2
• Atypical alveolar hyperplasia can progress to adenocarcinoma in situ in lung tissue 2
• Endometriosis is the precursor of endometrioid and clear cell carcinomas 5

Tumor Microenvironment

• Stromal microenvironment profoundly influences tumor progression 6
• Paracrine signaling between epithelial tumor cells and neighboring stromal fibroblasts mediates microenvironment influences 6
• Bidirectional interactions between cancer cells and fibroblasts affect various aspects of carcinoma formation 6
• Microenvironment affects efficiency of tumor formation, growth rate, invasiveness, and metastatic potential 6