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. 2018 Dec;16(6):7256-7263.
doi: 10.3892/ol.2018.9525. Epub 2018 Sep 28.

Focal Positivity of Immunohistochemical Markers for Pulmonary Squamous Cell Carcinoma in Primary Pulmonary Choriocarcinoma: A Histopathological Study

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Free PMC article

Focal Positivity of Immunohistochemical Markers for Pulmonary Squamous Cell Carcinoma in Primary Pulmonary Choriocarcinoma: A Histopathological Study

Susumu Matsukuma et al. Oncol Lett. .
Free PMC article

Abstract

Cytokeratin 5/6 (CK5/6), p63, and p40 are commonly used as immunohistochemical markers for squamous cell carcinoma (SqCC) of the lung. To elucidate their positivity in primary pulmonary choriocarcinoma (PPC), the present study examined 4 PPCs, including 1 surgically removed PPC and 3 postmortem PPCs. All PPCs consisted of nested cytotrophoblastic tumor cells and occasional syncytiotrophoblastic tumor cells although 1 surgically removed PPC was markedly affected by pre-operative therapy-associated necrosis and 3 postmortem PPCs coexisted with adenocarcinoma. In 1 surgical case, a pre-operative biopsy specimen of PPC contained a few polygonal tumor cells, which mimicked SqCC and exhibited focal p40+ features. Nuclear p63+ and p40+ features of cytotrophoblast-like polygonal tumor cells were focally observed in 3 PPCs (75%) and 2 PPCs (50%), respectively. CK5/6+ trophoblastic tumor cells were focally identified in 1 PPC. Additionally, in 2 other PPCs, CK5/6+ tumor cells were scattered in choriocarcinomatous areas, but possible intermingling of CK5/6+ adenocarcinoma cells could not be ruled out. The results emphasized that PPCs could mimic SqCC morphologically and immunohistochemically, although PPC was an extremely rare neoplasm. Surgical pathologists should be aware of this diagnostic pitfall when encountering a few squamous marker-positive polygonal tumor cells within hemorrhagic necrotic biopsy specimens from lung tumors.

Keywords: choriocarcinoma; cytokeratin 5/6; immunohistochemistry; lung; p40; p63; primary pulmonary choriocarcinoma; squamous cell carcinoma.

Figures

Figure 1.
Figure 1.
Pre-operative biopsy from a primary pulmonary choriocarcinoma in case 1. (A) Biopsy specimens containing a tiny tumor nest (arrow) and necrotic tissues (magnification, ×200). (B and C) High-power views [of area indicated by arrow in (A)] of (B) nested polygonal cells mimicking squamous cell carcinoma and (C) present focal p40+ nuclei (magnification, ×400).
Figure 2.
Figure 2.
Surgically removed primary PPC and postoperative biopsy of metastases in case 1. (A) Gross necrotic appearances of PPC. (B) PPC composed of marked necrosis and residual tumor cells (arrows; magnification, ×40). These residual tumor cells primarily consisted of (C) nested cytotrophoblast-like tumor cells and presented focal β-hCG positivity (inset). Immunostaining of the same areas revealed (D) p63+ nuclei and (E) p40+ nuclei of tumor cells (magnification, ×400). (F) PPC containing scattered mononuclear and multinucleated tumor cells and high-power views (inset). The same areas containing (G) β-hCG+ tumor cells and (H) CK5/6+ tumor cells, and insets depicting high-power views of positive cells (magnification, ×100, and ×400 for all insets). (I-K) Post-operative biopsy specimens of pulmonary metastasis mainly composed of (I) nested cytotrophoblast-like tumor cells, containing (J) scattered β-hCG+ cells and (K) showing diffuse p40+ nuclei (magnification, ×200). (L-O) Post-operative biopsy specimens of gastric metastasis consisting of (L) mononuclear and multinucleated tumor cells and (M) exhibiting β-hCG+ tumor cells, (N) p63+ tumor cells and (O) p40+ tumor cells (magnification, ×200). PPC, pulmonary choriocarcinoma; β-hCG, β-human chorionic gonadotropin; CK5/6, cytokeratin 5/6.
Figure 3.
Figure 3.
Combined primary PPC and adenocarcinoma in case 4. (A) PPC composed of cytotrophoblastic tumor cells and syncytiotrophoblastic tumor cells (arrow). (B and C) Immunostaining showing (B) β-hCG+ syncytiotrophoblasts and (C) CK5/6+ tumor cells (arrows). However, these CK5/6+ cells could not be discriminated from intermingled CK5/6+ adenocarcinoma cells (magnification, ×400). (D and E) Moderate-power views (D) of choriocarcinoma and adenocarcinoma cells exhibiting focal PAS+ lumina (D, inset; arrows). (E) CK5/6 immunostaining revealing positive adenocarcinoma cells (magnification, ×200 for D and E, and ×600 for D inset). (F-H) Concomitant adenocarcinoma cells in other areas (F) showing poorly differentiated features with occasional PAS+ lumina (F, inset; arrows). (G) CK5/6 immunostaining revealing positivity of adenocarcinoma cells and inner control basal cells of bronchioles (G, arrows). (H) TTF-1 immunostaining presenting negativity of adenocarcinoma cells but positivity of inner control cells of bronchioles (arrows; magnification, ×400). PPC, pulmonary choriocarcinoma; β-hCG, β-human chorionic gonadotropin; CK5/6, cytokeratin 5/6; PAS, periodic acid-Schiff; TTF-1, thyroid transcription factor-1.

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