Pathological snapshots of thymic epithelial tumors with invasion into neighboring structures: preparing for the forthcoming revision of the TNM classification

Abstract

Treatment decision-making of thymic epithelial tumors (TETs) after surgery is based on the pathological stage. Currently, most institutions use both the Masaoka-Koga system and the 8th edition of the tumor, node, metastasis (TNM) classification. Because these two systems separate each stage according to the same concept, namely, the "levels" of tumor extension, precise pathological evaluation of the presence or absence of tumor invasion into stage-defining structures is necessary. This review provides representative pathological snapshots of tumors invading neighboring structures to provide references that might be helpful to readers; the snapshots will cover features that correspond to those of "locally advanced TETs", the topic of this series. Tumor subtype, whether thymoma or thymic carcinoma, is another factor influencing treatment decisions. Accumulating evidence has indicated that most thymomas and thymic carcinomas have biologically distinct features. Representative results were achieved by a study conducted as part of The Cancer Genome Atlas (TCGA) project, and subsequent studies with the help of the TCGA data have further reported on these distinctive features. Here, we also introduce newly recognized features of TETs, mainly focusing on the difference between epithelial-rich thymomas and thymic squamous cell carcinoma. The new (9th) edition of the TNM classification will be launched in January 2024. Therefore, sharing current pathological features of TETs will help readers, not only in their daily practice but also in preparing for the upcoming classification system.

Keywords: Thymoma; the 8th edition of the TNM classification (TNM-8); the Masaoka-Koga stage classification; thymic carcinoma; thymic epithelial tumors (TETs).

Figure 1

Pathological snapshots of thymic epithelial tumors with invasion into stage-defining structures. (A) Type A thymoma with trans-capsular invasion. Note that the tumor (T) has a capsule in the corresponding area (dashed line) and penetrates it. (B) Type AB thymoma (mainly consisting of type B-like components) with a separate nodule (N) within the thick fibrous capsule (C). It should not be counted as trans-capsular invasion/stage II in the Masaoka-Koga system. (C) Type B2 thymoma (T) with mediastinal pleural (dashed line) involvement. (D) Type B1 thymoma (T) with pericardial invasion. The pericardium (P) is a distinctive fibrous structure and easily recognizable. (E) Type B3 thymoma (T) with pulmonary parenchymal invasion (L: lung). (F) Type B3 thymoma (T) that is attached to the lung (L) but does not penetrate into the outer elastin layer (dashed line) of the visceral pleura. This should not be regarded as lung invasion. A-E: hematoxylin and eosin staining; F: Elastica-Masson staining.

Figure 2

Pathological snapshots of thymic epithelial tumors with invasion into stage-defining structures (continued). (A) Type AB thymoma (T) with invasion into the wall of the SVC. (B) The wall of SVC (L: lumen). We assume that pathologists determine SVC invasion when tumors invade elastic layers (inner of the dashed line) of the wall. (C) Thymic neuroendocrine tumor (atypical carcinoid) (left upper and right lower: T) surrounding phrenic nerve (N). Although it is impossible to spare the nerve during surgery, by definition, this should not be considered phrenic nerve invasion. (D) Type B2 thymoma (T) with direct invasion into the diaphragm (D). (E,F) Thymic squamous cell carcinoma with esophagus invasion. Note the desmin (a smooth muscle marker) positive smooth muscle layer (F) of the esophagus invaded by the tumor (T) (biopsy for an inoperative case). A,C-E: hematoxylin and eosin staining; B: Elastica-Masson staining; F: immunohistochemical staining. SVC, superior vena cava.

Figure 3

Pathological snapshots of thymic epithelial tumors with metastases (hematoxylin and eosin staining). (A) Type B3 thymoma (T) with pleural implants (dashed line: lung pleura, L: lung). (B) Type A thymoma (T) with pulmonary metastases (pulmonary parenchymal nodules, L: lung). (C) Thymic squamous cell carcinoma (T) with LN metastases. (D) Type B1 thymoma (T) with liver (L) metastasis (biopsy sample). LN, lymph node.

Figure 4

Immunohistochemical staining for thymic squamous cell carcinoma. Thymic squamous cell carcinoma (T) with POU2F3 (A) and KIT (B) expression (the same case as Figure 2E,2F).