Small Cell Carcinoma – A Pathologic Survey

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  Slides from a Microsoft PowerPoint® presentation I delivered covering the basic clinical presentation, diagnosis, pathogenesis/pathophysiology, treatment, and prognosis of small cell cancer of the lung. This presentation was given on February 8, 2019 at the Medical College of Georgia, Augusta Campus to an audience of second-year MD candidates and a clinical pathologist.
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  • 1. Small Cell Carcinoma Jackson David Reynolds, BS, AS, AA Medical College of Georgia at Augusta University February 8, 2019 Bonert, 2014.
  • 2. Case Presentation: HPI & Physical Exam • A 61 y/o white M presents to his primary care physician c/o persistent non- productive cough, SOB, fatigue, and a 5 kg unintentional weight loss over the past 6 mo. • He has smoked ”at least” 2 PPD since age 14; denies EtOH or any illicit substance use. • Upon PE, he appears senescent beyond expectation for chronological age, & has a raspy vocal quality; A&O x4. • Monophonic wheeze & diminished lung sounds over the right upper and middle lobes. • Breath has the odor of cigarettes during PE. • Vitals: P = 85; RR = 23; BP = 129/79 mmHg; T = 37.1 ºC. 2Osmosis, 2018; Sarkar, et al., 2015; Tan, 2018.
  • 3. Differential Diagnosis • Pulmonary Malignancy (likely given smoking Hx). • Non-small cell lung CA (more common; somewhat less linked to smoking than small cell CA). • Squamous cell carcinoma (more linked to smoking). • Adenocarcinoma (less linked to smoking). • Small cell lung CA (Hx of smoking is a very strong risk factor). • Pulmonary hamartoma (less likely). • Benign. • Usually presents as a smooth growth on CXR. • Usually asymptomatic & found incidentally. • COPD (also likely given smoking Hx & may be comorbid w/main Dx). • Mediastinal lymphoma (less likely; usually affects pts in their 30s-40s). 3Khan, 2018; Smith, 2018; Tan, 2018.
  • 4. Case Presentation: Pertinent Labs & Studies • CXR shows mass in upper R lung. • Still need to d/dx b/w malignant & benign mass. • CBC: Mild normochromic, normocytic anemia. • LFTs: Unremarkable. • ↑ Serum LDH: 194 u/L (100-190). • Serum ALP: 55 u/L (39-117). • Core biopsy of mass tissue. • Preferred to FNA b/c larger in size. 4 American Cancer Society, Inc., 2016; Laboratory Corporation of America® Holdings, 2018; Melvil, 2018; Tan, 2018; University of Rochester Medical Center, 2018.
  • 5. Histopathology of Bx 5Rosen, 2008.
  • 6. Histopathology of Bx 6Di Muzio & Danaher, 2018; Jain, 2018; Rosen, 2008. • Histology: • Small, ovular cells. • Scant cytoplasm. • High mitotic count. • Gross: • White/tan. • Soft/friable. • No necrosis (yet…).
  • 7. Diagnosis: Small Cell Carcinoma • AKA “Oat Cell Carcinoma.” • LDH often only mildly elevated. • ALP typically NML. • Flow cytometry: • CD56+ (expressed by small cell CAs). • CD45- (d/dx from lymphoma, which is CD45+). 7Jain, 2018.
  • 8. Small Cell Carcinoma: Pathogenesis & Pathophysiology I • Neuroendocrine tumor (partially differentiated). • Arises from bronchial tissue. • Minority of lung CAs (most are “non-small cell”). • Most commonly arises in the lung, but (rarely) can also arise from prostatic, urinary bladder*, GI, or uterine cervical tissues. • Overwhelmingly associated w/cigarette smoking. • Radon exposure also implicated (though much less frequently). 8Bonert, 2014; Capizzello, et al., 2011; Jain, 2018; Nasu, et al., 2011; Tan, 2018. *The background image of the title slide is actually of small cell cancer of the urinary bladder.
  • 9. Small Cell Carcinoma: Pathogenesis & Pathophysiology II • Grows quickly & spreads rapidly. • But, ∴ ↑ responsiveness to ChemoTx. • Paraneoplastic syndromes sometimes arise. • Syndrome of Inappropriate Antidiuretic Hormone (SIADH). • Lambert-Eaton myasthenic syndrome (secondary to Abs against voltage- gated Ca+2 channels). • Cushing syndrome (secondary to ectopic ACTH-like secretion). • Most common lung CA subtype type that can produce necrosis. 9Di Muzio & Danaher, 2018; Tan, 2018.
  • 10. Small Cell Carcinoma: Additional Clinical Features • Unlike non-small cell carcinoma, only two stages: • Limited-Stage: Potentially Curable: • Limited to lung. • Extensive (metastatic): Incurable: • Paraneoplastic syndromes. • Incidence of distant metastasis at time of Dx: ~60%! • Common sites of metastases: • Liver. • Bone marrow. • Brain. • Adrenal gland(s). • Extrathoracic lymph nodes. 10Eldridge, 2018; Nakazawa, et al., 2011; Tan, 2018.
  • 11. Small Cell Carcinoma: Prognosis 11Eldridge, 2018; Nakazawa, et al., 2011; Tan, 2018. • Poor general prognostic factors: • Advanced age. • Poor overall health. • Sex (♂ = ↓ survival rate). • Continued smoking post-Dx. • Poor clinical prognostic factors: • Metastases. • ↑ serum LDH. • ↑ serum ALP. • ↓ serum albumin. • ↓ Hb. • Leukopenia.
  • 12. Small Cell Carcinoma: Prognosis • Limited-Stage: • w/Tx: • Median survival = 18-24 months. • Five-year survival rate = 19-31%. • Extensive (metastatic): • w/Tx: • Median survival = 6-12 months. • Five-year survival rate = 2-8%. • w/o Tx: Median survival = 2-4 months. 12Downward, 2017; Eldridge, 2018.
  • 13. Small Cell Carcinoma Treatment • Limited-Stage: Potentially Curable: • Tx: Combination ChemoTx & XRT. • Standard: Cisplatin plus etoposide or irinotecan. • Many other combinations utilized. • Smoking cessation associated w/increased survival. • Surgical resection (very uncommonly). • Extensive (metastatic): Incurable: • Palliative elective ChemoTx. • General palliative care (including palliative XRT) & hospice when indicated. Eldridge, 2018; Spataro, 2013; Tan, 2018; Tanoue, 2011; Vladivostok, 2013. Etoposide Molecular Model 13
  • 14. Our Patient: F/u 1 Year Post-Dx 14 Despite an initially favorable response to combination chemoTx & XRT and total abstinence from tobacco, PET- CT showed that prolific metastases had developed in our pt’s liver, L femur, and brain. He elected to end chemoTx & XRT and hospice care was begun. He died six months later.
  • 15. Summary Bernhardt & Shadia, 2016; Eldridge, 2018; Osmosis, 2018. Diagnosis • Small Cell Carcinoma (Limited- Stage). • Progressed to Extensive-Stage. Treatment • Combo ChemoTx w/Cisplatin + Etoposide & XRT. • Smoking Cessation. Prognosis • Variable, though generally poor, even in the context of aggressive Tx measures. Conclusion • Small cell carcinoma is an extremely serious malignancy w/an overall grim prognosis, even w/proper treatment. Don’t smoke. 15
  • 16. Question 1 Bonert, 2014. A 71 y/o M pt, Robert Myers, a factory worker and 2 PPD cigarette smoker since age 17, presents to his PCP c/o SOB, severe fatigue, “yellow skin,” vision changes, “easy bleeding,” and marked weight loss over the past month. Blood is drawn and a CXR is ordered. Multiple lung lesions on CXR prompt a Bx and subsequent flow cytometry which showed small cell carcinoma. A PET-CT is performed which shows what appear to be profound mets to the brain and liver. Which of the following is most accurate regarding his prognosis? A. Combo ChemoTx w/Cisplatin + etoposide will dramatically extend survival over non-Tx. B. Combo ChemoTx w/Cisplatin + etoposide will dramatically improve his life expectancy, but only if coupled w/immediate and total smoking cessation. C. Median five-year survival for a patient like Mr. Myers is unlikely to exceed 18 months, w/ or w/o Tx. D. Mets to brain and liver are more easily Tx’d than the the primary pulmonary malignancies, but often recur. E. While mets are extensive, small cell carcinoma is a largely indolent malignancy, so ChemoTx and XRT are both likely to be curative over an extended period. 16
  • 17. Question 2 Bonert, 2014. Bill Vance is an 83 y/o M pt who was Dx’d w/limited-stage small cell carcinoma of the lung a year and a half ago. He elected to forgo any aggressive Tx, instead opting solely for palliative measures. He was placed on in-home hospice care six weeks ago. He is brought via EMS to the ED following a seizure which was preceded by an episode of violent emesis. His skin is dark and he has scleral icterus. HR = 59; RR = 21; BP = 106/80; GCS = 4. Which of the following best explains this suite of Sx? A. Mets to bone, liver, and adrenal glands. B. Mets to brain and liver. C. Mets to thyroid and parathyroid glands leading to hypometabolism and calcium imbalance. D. Necrosis of the primary tumor. E. Paraneoplastic syndrome leading to adrenal gland overactivity. F. Paraneoplastic syndrome leading to hepatic failure and GI upset. 17
  • 18. References I American Cancer Society, Inc. . “Tests for Small Cell Lung Cancer.” American Cancer Society, American Cancer Society, Inc. , 16 May 2016, www.cancer.org/cancer/small-cell-lung-cancer/detection-diagnosis-staging/how-diagnosed.html. Bernhardt, Erica B., and Shadia I. Jalal. “Small Cell Lung Cancer.” Cancer Treatment and Research Lung Cancer, 2016, pp. 301–322., doi:10.1007/978- 3-319-40389-2_14. Bonert, Michael. Small Cell Carcinoma of the Urinary Bladder -- High Mag. 6 Jan. 2014, commons.wikimedia.org/wiki/File:Small_cell_carcinoma_of_the_urinary_bladder_--_high_mag.jpg. Byers, Lauren Averett, and Charles M. Rudin. “Small Cell Lung Cancer: Where Do We Go from Here?” Cancer, vol. 121, no. 5, 2014, pp. 664–672., doi:10.1002/cncr.29098. Capizzello, Antonio, et al. “Pure Small Cell Carcinoma of the Prostate: A Case Report and Literature Review.” Case Reports in Oncology, vol. 4, no. 1, 2011, pp. 88–95., doi:10.1159/000324717. Cornfield, Dennis, et al. “The Potential Role of Flow Cytometry in the Diagnosis of Small Cell Carcinoma.” Archives of Pathology & Laboratory Medicine, vol. 127, no. 4, Apr. 2003, pp. 461–464. Di Muzio, Bruno, and Luke Danahaer. “Small-Cell Lung Cancer | Radiology Reference Article.” Radiopaedia.org, Radiopaedia.org, 2018, radiopaedia.org/articles/small-cell-lung-cancer-2. Downward, Emily. “Small Cell Lung Cancer Staging.” LungCancer.net, Health Union, LLC, Jan. 2017, lungcancer.net/basics/small-cell-staging/. Eldridge, Lynne. “What You Should Know About Extensive Small Cell Lung Cancer.” Verywell Health, Verywellhealth, 30 Sept. 2018, www.verywellhealth.com/extensive-stage-small-cell-lung-cancer-2249370. Jain, Deepali. “Small Cell Carcinoma.” Pathology Outlines - PathologyOutlines.com, PathologyOutlines.com, Inc., 5 Sept. 2018, www.pathologyoutlines.com/topic/lungtumorsmallcell.html. Khan, Ali Nawaz. “Lung Hamartoma Imaging .” Medscape, Medscape, 16 Oct. 2018, emedicine.medscape.com/article/356271-overview. Laboratory Corporation of America® Holdings. “Alkaline Phosphatase.” LabCorp, Laboratory Corporation of America® Holdings, 2018, www.labcorp.com/test-menu/19016/alkaline-phosphatase#. 18
  • 19. References II Melvil. “LK-Small cell3683.” Wikimedia Commons, Melvil, 17 May 2013, commons.wikimedia.org/wiki/File:LK-small_cell3683.jpg. Nakazawa, Kensuke, et al. “Specific Organ Metastases and Survival in Small Cell Lung Cancer.” Oncology Letters, vol. 4, no. 4, 2012, pp. 617–620., doi:10.3892/ol.2012.792. Nasu, Kaei, et al. “Advanced Small Cell Carcinoma of the Uterine Cervix Treated by Neoadjuvant Chemotherapy with Irinotecan and Cisplatin Followed by Radical Surgery.” Rare Tumors, vol. 3, no. 1, 2011, pp. 18–20., doi:10.4081/rt.2011.e6. Osmosis, director. Lung Cancer - Causes, Symptoms, Diagnosis, Treatment, Pathology. YouTube, Osmosis, 28 Mar. 2018, www.youtube.com/watch?v=nQQFDvQqw9A. Procinemastock. “Portrait of Old Wrinkled and Gray-Haired Old Man with Close.” Storyblocks Videoblocks, Procinemastock, 2018, www.videoblocks.com/video/portrait-of-old-wrinkled-and-gray-haired-old-man-with-close-4k-raw-video-record-njgzir19gikc7cdtx. Rosen, Yale. “Small Cell Carcinoma.” Flickr, Yale Rosen, 20 Mar. 2008, www.flickr.com/photos/pulmonary_pathology/3931156869/. Sarkar, Malay, et al. “Auscultation of the Respiratory System.” Annals of Thoracic Medicine, vol. 10, no. 3, 2015, p. 158., doi:10.4103/1817-1737.160831. Smith, Sonali M. “Mediastinal Lymphoma.” Medscape, Medscape, 2 July 2018, emedicine.medscape.com/article/203681-overview. Spataro, Karen. “Cisplatin.” Indiana University Melvin and Bren Simon Cancer Center , The Trustees of Indiana University, 12 Sept. 2013, cancer.iu.edu/breakthroughs/breakthroughs/story5.shtml. Tan, Winston W. “Small Cell Lung Cancer.” Medscape, 16 Oct. 2018, emedicine.medscape.com/article/280104-overview. Tanoue, L. T. “Influence of Smoking Cessation after Diagnosis of Early Stage Lung Cancer on Prognosis: Systematic Review of Observational Studies with Meta-Analysis.” Yearbook of Pulmonary Disease, vol. 2011, 2011, pp. 104–106., doi:10.1016/j.ypdi.2011.04.001. University of Rochester Medical Center. “Lactic Acid Dehydrogenase (Blood).” Health Encyclopedia, University of Rochester Medical Center, 2018, www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=lactic_acid_dehydrogenase_blood. Vladivostok, Marina. “Ball-and-Stick Model of Etoposide Molecule.” Wikipedia, Wikipedia, 28 July 2013, www.wikiwand.com/en/Etoposide. 19
  • 20. Thank You Bonert, 2014.
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