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Diagnosis and Discussion - Case 1130

Discussion

The case findings are discussed in the questions below.

Question 1. The H&E image(s) demonstrate the presence of neoplastic large cells, with bizarre nuclei and frequent mitoses. Additionally identified are areas of atypical spindle cell proliferations. Based on these findings, you suspect the possibility of pleomorphic carcinoma of the lung. Which of the following best describes your preliminary diagnosis:

A. A large cell neuroendocrine carcinoma with spindle cell component.

Incorrect. Neuroendocrine carcinomas with spindle cell components do not fall under the umbrella category of Pleomorphic carcinoma in the current WHO classification.

B. A poorly differentiated carcinoma with spindle cell components.

Correct. The WHO defines Pleomorphic carcinoma of the lung as “a poorly differentiated non-small cell lung carcinoma (non-small cell carcinoma [NSCC], including adenocarcinoma, squamous cell carcinoma [SCC], and/or large cell carcinoma [LCC]) containing at least a 10% component of spindle and/or giant cells, or a carcinoma that consists entirely of spindle and/or neoplastic giant cells.”(1)

C. A poorly differentiated carcinoma with rhabdoid features.

Incorrect. This description may raise your suspicion for other entities, including one added to the 2021 WHO update on thoracic tumors, namely the SMARCA4 deficient undifferentiated tumor.

D. A large cell neuroendocrine carcinoma with spindle cell component.

Incorrect. Neuroendocrine carcinomas with spindle cell components do not fall under the umbrella category of pleomorphic carcinoma within the current WHO classification.

Question 2. Which of the following immunostains could stain positive in areas represented by image 1, but would be expected to stain negative in areas represented by images 2 and 3?

A. TTF-1

Correct. TTF-1 may be positive in an adenocarcinoma component of pleomorphic carcinoma; however, TTF-1 is expected to be predominantly negative in pleomorphic carcinoma, including giant cell and spindle cell components. This description also applies to immunostaining for Napsin A.

B. Synaptophysin

Incorrect. Synaptophysin would be expected to stain neuroendocrine cells, which are not seen in image 1 or image 2. Additionally, neuroendocrine carcinomas with spindle cell components do not fall under the umbrella category of pleomorphic carcinoma within the current WHO classification.

C. Beta-HCG

Incorrect. Beta-HCG production by a pleomorphic carcinoma is rare. While it can be expressed (again, rarely) in both the giant cell and spindle cell components, its utility in identification of pleomorphic carcinoma is not yet clear, and its use is limited to case reports.

D. p40

Incorrect. p40 and p63 are expected to be positive in squamous cell carcinoma; however, they are predominantly negative in pleomorphic carcinoma. When positive, it is expected to be seen within a squamous cell carcinoma component.

E. p63

 Incorrect. See explanation immediately above.

Question 3. Which of the following methods is the least invasive method to diagnose pleomorphic carcinoma of the lung?

A. Resection (entire lesion)

Correct. According to WHO, “The definitive diagnosis of pleomorphic carcinoma may be rendered only in surgical specimens.” Biopsy and cytologic specimens may raise suspicion for a pleomorphic carcinoma of the lung. Definitive diagnosis requires a surgical specimen, in order to accurately quantify the different components of the carcinoma. A pleomorphic carcinoma contains at least 10% (and up to 100%) of a spindle cell and/or giant cell component. Other components that are frequently present in specimens include squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, which are present in up to 26%, 43% and 72% of specimens, respectively (1, 4, 5, and 6).

B. Fine needle aspiration

Incorrect. See explanation for answer ‘A’.

C. Biopsy

Incorrect. See explanation for answer ‘A’.

Question 4. What are the United States Preventative Services Task Force (USPSTF) indications for low-dose computed tomography (LDCT) screening for lung cancer?

A. Adults aged 40-70 with a 20 pack-year smoking history.

Incorrect. See explanation for answer ‘C’.

B. Adults aged 50-70 with a 15 pack-year smoking history.

Incorrect. See explanation for answer ‘C’.

C. Adults aged 50-80 with a 20 pack-year smoking history.

Correct. The current USPSTF recommendations are “annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.” (7).

D. Adults aged 50-80 with a 15 pack-year smoking history.

Incorrect. See explanation for answer ‘C’.

Question 5. Per the current USPSTF guidelines, how often should a patient with at least a 20 pack-year history of smoking be screened for lung cancer by low-dose computed tomography (LDCT)?

A. Once, after age 50.

Incorrect. See explanation for ‘C’.

B. Once every five years, until 15 years after smoking cessation.

Incorrect. See explanation for ‘C’.

C. Once a year, until 15 years after smoking cessation.

Correct. The current USPSTF recommendations are “annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.” (7).

D. Once a year, until smoking cessation.

Incorrect. See explanation for ‘C’.

References

  1. Rossi, G, Boland JM, Pelosi, G, et al. Pleomorphic carcinoma of the lung. In: WHO Classification of Tumours Editorial Board. Thoracic tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2021 [cited 2024 February 27]. (WHO classification of tumours series, 5th ed.; vol. 5). Available from: https://tumourclassification.iarc.who.int/chapters/35.
  2. Dinis de Sousa M, Barata M, Miranda AR, et al. Beta-HCG secretion by a pulmonary pleomorphic carcinoma: A case report. Respir Med Case Rep. 2021 Oct 21;34:101528. doi: 10.1016/j.rmcr.2021.101528. PMID: 34754749; PMCID: PMC8556653.
  3. Hirano H, Yoshida T, Sakamoto T, et al. Pulmonary pleomorphic carcinoma producing hCG. Pathol Int. 2007 Oct;57(10):698-702. doi: 10.1111/j.1440-1827.2007.02160.x. PMID: 17803660.
  4. Rossi G, Cavazza A, Sturm N, et al. Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases. Am J Surg Pathol. 2003 Mar;27(3):311-24. doi: 10.1097/00000478-200303000-00004. PMID: 12604887.
  5. Pelosi G, Fraggetta F, Nappi O, et al. Pleomorphic carcinomas of the lung show a selective distribution of gene products involved in cell differentiation, cell cycle control, tumor growth, and tumor cell motility: a clinicopathologic and immunohistochemical study of 31 cases. Am J Surg Pathol. 2003 Sep;27(9):1203-15. doi: 10.1097/00000478-200309000-00003. PMID: 12960804.
  6. Pelosi G, Sonzogni A, De Pas T, et al. Review article: pulmonary sarcomatoid carcinomas: a practical overview. Int J Surg Pathol. 2010 Apr;18(2):103-20. doi: 10.1177/1066896908330049. Epub 2009 Jan 4. PMID: 19124452.
  7. U.S. Preventive Services Task Force. Recommendation: Lung Cancer: Screening [Internet].  Rockville, MD (United States of America): USPSTF; 2021 March 09 [cited 2024 February 2]. (Final Recommendation Statement. Lung Cancer: Screening). Available from:  https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening.