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squamous cell carcinoma, lung

Epidemiology: 1) age > 50 years 2) occurs predominantly in smokers Pathology: 1) 50-65% arise in a major bronchus 2) may also arise in upper airway or esophagus 3) metastases to the brain (15%) 4) hypercalcemia due to parathyroid hormone-related peptide Genetics: - HERV-H 19p13.11 provirus ancestral Env polyprotein may be overexpressed - other implicated genes (also see lung cancer) Clinical manifestations: 1) occur early because of proximal bronchial involvement 2) cough 3) hemoptysis 4) post-obstructive pneumonia from lobar/segmental collapse 5) cerebellar ataxia (uncommon) 6) epidermolysis bullosa (uncommon) Laboratory: 1) sputum cytology - centrally located endobronchial squamous cell carcinomas may exfoliate malignant cells into sputum 2) serum calcium: hypercalcemia (25%) - serum PTH low with hypercalcemia of malignancy - serum PTH-related peptide high with hypercalcemia of malignancy 3) serum glucose - hypoglycemia from secretion of insulin-like polypeptide 4) EGFR gene mutation (not indicated in smokers) [2] 5) increased C-reactive protein in serum associated with increased risk for lung squamous cell carcinoma is smokers & former smokers, but not never smokers [5] Special laboratory: - see lung carcinoma Radiology: - chest X-ray a) atelectasis (23%) b) obstructive pneumonitis (13%) c) hilar adenopathy (38%) d) cavitation (5-30%) e) 1/3 of cases present with peripheral lesions - computed tomography of chest (image [4]) Management: 1) resection, radiation & chemotherapy - platinum-based chemotherapy for resected stage II [2] - platinum-based chemotherapy combined with gemcitabine* [2] - 4-6 cycles - platinum-based chemotherapy combined with paclitaxel/nab-paclitaxel + sintilimab [6] - concurrent chemotherapy & radiation therapy over 6 weeks treatment of choice for patients with bulky or inoperable stage IIIA or IIIB disease [3] - carboplatin + paclitaxel 4-6 cycles for metastatic SCC [3] - avoid bevacizumab, risk of pulmonary hemorrhage in patients with SCC [3] 2) maintenance chemotherapy - switch-maintenance therapy with erlotinib only FDA-approved option for SCC - pemetrexed not an option with SCC - role of maintenance chemotherapy in metastatic SCC unclear 3) laser bronchoscopy & endobronchial brachytherapy are palliative measures 4) palliative chemotherapy with carboplatin & gemcitabine 5) resectable brain metastasis is followed with whole brain radiation therapy 6) palliative care consultation on diagnosis of metastases [2] * switch gemcitabine to vinorelbine if patient develops TTP

Interactions

disease interactions

Specific

spindle cell (squamous) carcinoma (carcinosarcoma, sarcomatoid carcinoma)

General

carcinoma of the lung squamous cell carcinoma (SCC)

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 768
  2. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18, 19. American College of Physicians, Philadelphia 2012, 2015, 2018, 2021.
  3. Lim MY Non-Small Cell Lung Cancer: 5 Management Challenges. Medscape. Nov 30, 2016 http://reference.medscape.com/features/slideshow/non-small-cell-lung-cancer
  4. Conti L, Gatt S Images in Clinical Medicine: Squamous-Cell Carcinoma of the Lung. N Engl J Med 2018; 379:e17 PMID: 30207918 https://www.nejm.org/doi/full/10.1056/NEJMicm1802514
  5. Muller DC, Larose TL, Hodge A et al Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: nested case-control study within Lung Cancer Cohort Consortium BMJ 2019;364:k4981 PMID: 30606716 https://www.bmj.com/content/364/bmj.k4981
  6. Davenport L Triple Therapy for Squamous NSCLC Shows Real-World Clinical Benefit. Medscape. December 23, 2021 https://www.medscape.com/viewarticle/965488