Lymphatic endothelial cancerization in papillary thyroid carcinoma: Hidden evidence of lymphatic invasion

Abstract

We hypothesize that cystic structures in metastatic papillary thyroid carcinoma (PTC) develop along the framework of lymphatic channels. To investigate this phenomenon, different categories of PTC were immunostained for D2-40 and TTF1. In this study, reactivity for D2-40 was considered as positive when there is membranous staining as often seen in lymphatic endothelial cells. Thirty cases of PTC with lymph node metastasis or with potential for lymphatic invasion and 20 cases metastatic PTC in lymph nodes were reviewed and found to show double/mosaic immunoreactivity for TTF1/D2-40 in 40-100% of cases. PTC metastasis in lymph nodes with cysts and some branching lymphatic-like channels lined by follicular cells with or without nuclear features of PTC were diffusely reactive to TTF1, and focally to D2-40. For primary and metastatic PTC, focal membranous D2-40 reactivity was also demonstrated in cysts or cleft linings. For25 thyroid neoplasms with no known potential for lymphatic invasion, there was no such immunoreactivity. The mosaic or double immunoreactivity for TTF1/ D2-40 suggests lymphatic cancerization and possible endothelial mimicry of follicular cells. Mosaic/double immunoreactivity is helpful to detect the hidden pattern of lymphatic invasion masquerading as 'benign-appearing' follicles and supports our hypothesis of malignant cells developing along the lymphatic framework.Key words: carcinoma, lymphatic, mimicry, papillary, thyroid Papillary thyroid carcinoma (PTC) is known for its high potential for lymph node metastasis. Lymphatic vessel invasion of the thyroid parenchyma is not often readily identified, even in cases of PTC associated with lymph node metastasis. Regardless of the histologic architecture within the thyroid, non-encapsulated PTC occasionally gives rise to cystic metastasis in cervical lymph nodes.1-3 Due to the minimal solid component, the cystic lymph node metastases can mimic benign cysts of the neck containing thyroid tissue or benign ectopic thyroid tissue.2,3 The mechanism of cystic development in metastatic PTC is poorly understood and has not been investigated. In addition, morphologic comparison of cystic metastatic PTC in lymph nodes with cystic lymphangioma demonstrates some remarkable similarities in architecture. We hypothesize that the cystic structure in metastatic PTC develops along the framework of lymphatic channels in the lymph node. This lymphatic endothelial cancerization in PTC may represent a hidden mechanism of lymphatic invasion. In this study, we first investigate the histopathogenesis of cystic metastatic PTC by performing the immunostaining for TTF1 (thyroid transcription factor-1) and D2-40. Subsequently, we investigate the same phenomenon of lymphatic endothelial cancerization in primary PTC. To determine the sensitivity and the specificity of the immunostaining in identifying lymphatic endothelial cancerization, we expand the immunostaining to different types of thyroid lesion. MATERIALS AND METHODSEthics approval from the investigational review board of o...

Desmin and CD31 immunolabeling for detecting venous invasion of the pancreatobiliary tract cancers

“…However, CD31 labeling was not helpful for identifying the IN-like and destructive patterns because of partial or total loss of CD31 expression on the endothelial side of the venous wall. This loss of CD31 expression of endothelial labeling in cancer invasion foci was previously described in lymphatics of papillary thyroid carcinoma and was explained as endothelial cancerization [16]. Similarly, we also observed that CD31 expression was lost at the points at which the cancer-cell clusters attached to the intimal layer of Patients with pancreatobiliary tract cancer and venous invasion detected by H&E staining have significantly worse disease-free survival (3-year survival rate, 23%) than those without VI (46%; P = 0.016).…”

Lymphatic Vessel Invasion in Routine Pathology Reports of Papillary Thyroid Cancer

“…Pathologic reassessment of 22 specimens including 13 L0, 2 L1, and seven tumors with no LVI documentation was performed by two independent, experienced pathologists. No cases showed LVI diagnosis according to the current definition [presence of tumor tissue and/or psammoma bodies in lymphatic spaces, including lymphatic spaces within the tumor, but also at the periphery of the tumor, or somewhere else in the resection specimen ( 29 )], despite nodal involvement. Two cases, which had originally been reported as L1 ( Supplementary Table 3 ), could not be confirmed as L1.…”

“…LVI (L-status; L1 = invasion and L0 = no invasion) is not regularly included in pathology reports in PTC in Europe, as it is not mandatory to report LVI according to the current TNM classification ( 28 ). One possible explanation is that LVI in PTC is often not easily identified in thyroid parenchyma ( Figure 1 ) ( 29 ).…”

“…Lymphatic vessel invasion is defined as “ tumor deposits within lymphatic spaces ” that may manifest “ as psammoma bodies alone within these spaces ” ( 27 , 30 , 31 ). However, often the invaded lymph vascular channels are overgrown by the tumor, as evidenced by the absence of lymphatic channels in the central part of most PTCs with lymph node metastases ( 29 ). The thin walls of the lymphatic vascular channels and the invasive nature of the tumors are factors, which can make LVI detection challenging ( Figure 1 ).…”

Liquid Isolation to Optimize Ultrasonic Display of Cervical Lymphatic Vessels

“…L ymphatic vessels are the only pathway for lymphatic fluid to flow into venous bloodstream, and they are also one of the main channels for the migration and metastasis of malignant tumor cells [1]. Among the various neck malignancies, differentiated thyroid carcinomas (DTCs) are characterized by metastases to regional lymph nodes via lymphatic vessels [2,3]. Although high-frequency ultrasound imaging has become the first choice for examination and preliminary assessment of cervical lymph nodes, obviously its capacity of displaying the lymphatic vessels is still insufficient up to date [4].…”