Pulmonary Pathology Society

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May, 2024
Case of the Month

Clinical History:
A middle-aged non-smoking woman with history of untreated asthma upon exertion underwent a CT scan for a respiratory tract infection, which led to the incidental discovery of a 10mm solid lung nodule in the left upper lobe. The lesion was stable on follow-up and was removed in a segmentectomy 2 years later upon patient request.

Macroscopically, the nodule was well-circumscribed, tan-white with a homogenous consistency. An intraoperative frozen section was performed (Figure 1 and 2). Representative histological images (Figure 3-5) and immunohistochemical stains are provided (Figure 6-8).

Q1. What is the most likely diagnosis

Sclerosing pneumocytoma
Pleomorphic carcinoma of the lung
Carcinoid tumor of the lung
Pulmonary hamartoma

Q2. Which of the following immunohistochemical markers is most likely to be strongly positive in both neoplastic cell populations?

CK7
EMA
Synaptophysin
ER

Q3. Which genetic alteration is most likely to be found in this lesion?

KRAS
MEN1
AKT1
EGFR

Answers to Quiz

Q1. A
Q2. B
Q3. C

Diagnosis

Sclerosing pneumoctyoma

Discussion

Frozen section (Figure 1 and 2) showed a well demarcated tumor with presumably solid growth pattern, pleomorphism, but no overt mitotic activity. On the definitive sections, the tumor nodule was well-circumscribed (Figure 3), featuring minor sclerotic areas and a predominantly solid growth pattern (Figure 4). The neoplastic cells showed abundant eosinophilic cytoplasm, but also nuclear pleomorphism without mitotic activity (Figure 5). The few acinar/papillary areas present and depicted in Figure 5 were better visible using immunohistochemical staining. Immunohistochemistry (Figure 6 and 7) helped to identify the presence of two distinct neoplastic cell types, consisting of surface cells (TTF1+, EMA+, AE1/AE3+) and round stromal cells (TTF1+, EMA+, CK AE1/AE3 very weakly). Molecular analysis confirmed an AKT1 mutation.

Sclerosing pneumocytoma is a benign pulmonary neoplasm with an unknown pathogenesis, presumably deriving from primitive pulmonary epithelium. Nearly all sclerosing pneumocytomas harbor AKT1 alterations, which can be useful for diagnosis confirmation. The essential diagnostic criteria according to WHO 2021 are the presence of a well-circumscribed lesion composed of a dual population of cuboidal surface cells and stromal round cells, usually featuring a mixture of papillary, sclerotic, solid, and hemorrhagic growth patterns. The distinctive immunostaining profile of TTF1-and EMA-positivity in both surface and round cells and absence or weak staining of cytokeratin in the round cells, while the surface cells are strongly positive, is desirable.

The clinical course is typically indolent, with most lesions being discovered incidentally, as in the current case. However, cases with recurrence, malignant transformation and lymph node and distant metastases have been described. Rarely sclerosing pneumocytoma may co-exist with carcinoid tumors or adenocarcinoma.

Treatment consists of surgical resection, which is usually curative.

Take home message for trainees:
The presence of a well-circumscribed tumor with a dual cell population in a non-smoker should raise the suspicion for sclerosing pneumocytoma. Significant cell atypia can present a diagnostic pitfall, especially on intraoperative frozen section.

References

Beasley MB, Chou TY, Soares FA, et al. Sclerosing pneumocytoma. In: WHO Classification of Tumours Editorial Board. Thoracic tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2021 (WHO classification of tumours series, 5th ed.; vol. 5).

Miyagawa-Hayashino A, Tazelaar HD, Langel DJ, Colby TV. Pulmonary sclerosing hemangioma with lymph node metastases: report of 4 cases. Arch Pathol Lab Med. 2003 Mar;127(3):321-5.

Wang X, Ng CS, Shi X, Yin W. Characteristics of metastatic and nonmetastatic pulmonary sclerosing pneumocytomas: a clinicopathological study of 68 cases and 15 reported metastatic cases. Lab Invest. 2023 Jul;103(7):100135.

Yeh YC, Chu PY, Lin SY, et al. Comprehensive genomic and transcriptomic analysis of sclerosing pneumocytoma. Mod Pathol. 2024 Jan;37(1):100354.

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