What is carcinoma and how is it treated?

Carcinoma: Definition and Treatment Approaches

Carcinoma is a type of cancer that originates from epithelial cells lining organs or tissues, and treatment should be tailored to the specific type, location, and stage of carcinoma to optimize patient outcomes including mortality, morbidity, and quality of life.

Definition and Characteristics

• Carcinoma is defined as cancer arising from epithelial cells that line organs or tissues, representing the most common type of human malignancy 1
• Carcinomas typically begin as clonal proliferation of cells with acquired mutations, progressing to invasive carcinoma when cells breach the underlying basement membrane 1
• The transition to invasive carcinoma carries the potential for vascular or lymphatic invasion, leading to metastasis to lymph nodes or distant tissues 1
• Ultraviolet radiation has been implicated in DNA damage leading to carcinomas, particularly in skin cancer but potentially in other epithelial tissues 2

Classification of Carcinomas

• Carcinomas can be classified based on histological features and tissue of origin, with adenocarcinomas (arising from specialized epithelial cells lining ducts of major organs) being the most common type 3
• The breakdown of epithelial cell homeostasis leading to aggressive cancer progression correlates with loss of epithelial characteristics and acquisition of a migratory phenotype, known as epithelial to mesenchymal transition (EMT) 4
• Histologic diagnosis is rendered based on cytologic and architectural features of the tumor, location of proliferating cells, and interaction with surrounding stromal elements 1

Diagnostic Approach

• Comprehensive pathology reporting is essential, including determination of histologic type, hormone receptor status (for applicable carcinomas), HER2 status, tumor grade, size, and lymph node involvement 5
• For metastatic disease, biopsy of accessible metastatic lesions is recommended to confirm diagnosis and reassess biological markers 5
• Accurate pathology reporting requires communication between clinician and pathologist about relevant patient history and specific requests for biomarker determination 6
• The College of American Pathologists (CAP) has developed standardized pathology reporting protocols that are endorsed for complete and consistent reporting of malignant specimens 6

Treatment Principles

• Treatment of carcinoma involves local therapy (surgery, radiotherapy, or both) and systemic therapy (cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations) 6
• Treatment decisions should be based on prognostic and predictive factors including tumor histology, clinical and pathologic characteristics, lymph node status, hormone receptor content (where applicable), HER2 status, presence of metastatic disease, patient comorbidities, age, and menopausal status 6
• A multidisciplinary team approach is recommended, integrating medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy 5

Treatment by Carcinoma Subtype

Breast Carcinoma

• Breast carcinoma treatment includes surgery (breast-conserving surgery with radiation or mastectomy), systemic therapy (chemotherapy, endocrine therapy, targeted therapy), and radiation therapy 6, 5
• For hormone receptor-positive breast carcinoma, adjuvant endocrine therapy is recommended to reduce recurrence risk 5
• For HER2-positive breast carcinoma, HER2-directed therapy should be offered to all patients 5
• For triple-negative breast carcinoma, chemotherapy is the mainstay of treatment 5

Carcinoma of Unknown Primary Site

• Diagnostic strategy should aim to identify anatomoclinical entities of carcinomas of unknown primary site for which there is specific treatment 6
• Main differential diagnoses for patients with carcinomas of unknown primary site are extragonadal germ cell tumor and lymphoma, as they are potentially curable 6
• Treatment should be tailored based on recognition of well-defined clinicopathologic subsets that differ in prognosis 6
• Best prognostic factors include general good health status, female gender, lymph node metastases, neuroendocrine or squamous cell carcinoma, and few metastatic sites 6

Treatment of Specific Carcinoma Types

Neuroendocrine Carcinoma

• Management should consider cellular differentiation 6
• Poorly differentiated forms are chemosensitive, with treatment typically based on platinum salt and etoposide combination 6
• For well-differentiated forms, treatment decisions should be based on multidisciplinary consideration of patient's symptoms and disease progression 6

Squamous Cell Carcinoma with Cervical Lymph Node Metastases

• Patients should receive lymph node dissection and complementary radiotherapy 6
• If surgery is not possible, radiotherapy should be performed 6
• Chemotherapy can be proposed for tumors not suitable for resection or surgery 6

Advanced/Metastatic Carcinoma

• For metastatic disease, the primary goals of systemic treatment are palliating symptoms, prolonging survival, and maintaining or improving quality of life 5
• For patients with metastatic disease and intact primary tumor, the primary approach is systemic therapy, with surgery considered for palliation of symptoms or impending complications 5
• Evaluation of response to therapy should occur every 2-4 months for endocrine therapy and after 2-4 cycles for chemotherapy in metastatic setting 5
• Carboplatin is indicated for the palliative treatment of patients with recurrent ovarian carcinoma, including those previously treated with cisplatin 7

Monitoring and Follow-up

• Regular clinical assessments should be performed during follow-up to provide optimal symptom management and maintain quality of life 5
• Circulating tumor cells (CTCs) are being explored as potential biomarkers for early detection of metastases and monitoring efficacy of systemic therapy 8
• For breast carcinoma follow-up, interval history and physical exam every 4-6 months for 5 years, then every 12 months, as well as annual mammography of the contralateral breast is recommended 9

Emerging Therapies

• Immunotherapy approaches including CAR-T cell therapy have shown success in certain hematologic malignancies but face challenges in treating solid carcinomas 3
• Novel strategies are being developed to manage side effects associated with immunotherapeutic approaches 3
• Analysis of molecular mechanisms involved in epithelial to mesenchymal transition might yield novel therapeutic targets for aggressive carcinomas 4