Challenges in Cytology Specimens With Hürthle Cells

In fine-needle aspirations (FNA) of thyroid, Hürthle cells can be found in a broad spectrum of lesions, ranging from non-neoplastic conditions to aggressive malignant tumors. Recognize them morphologically, frequently represents a challenging for an adequately diagnosis and are associated with a significant interobserver variability. Although the limitations of the morphologic diagnosis still exist, the interpretation of the context where the cells appear and the recent advances in the molecular knowledge of Hürthle cells tumors are contributing for a more precise diagnosis. This review aims to describe the cytology aspects of all Hürthle cells neoplastic and non-neoplastic thyroid lesions, focusing on the differential diagnosis and reporting according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC). New entities according to the latest World Health Organization (WHO) classification are included, as well as an update of the current molecular data.This work was partially supported by Portuguese funds through FCT—Fundação para a Ciencia e a Tecnologia—in the framework of a PhD grant to SC (SFRH/BD/147650/2019)

Collision sellar lesions: experience with eight cases and review of the literature

The concomitant presence of a pituitary adenoma with a second sellar lesion in patients operated upon for pituitary adenoma is an uncommon entity. Although rare, quite a great variety of lesions have been indentified coexisting with pituitary adenomas. In fact, most combinations have been described before, but an overview with information on the frequency of combined pathologies in a large series has not been published. We present a series of eight collision sellar lesions indentified among 548 transsphenoidally resected pituitary adenomas in two Neurosurgical Departments. The histological studies confirmed a case of sarcoidosis within a non-functioning pituitary adenoma, a case of intrasellar schwannoma coexisting with growth hormone (GH) secreting adenoma, two Rathke’s cleft cysts combined with pituitary adenomas, three gangliocytomas associated with GH-secreting adenomas, and a case of a double pituitary adenoma. The pertinent literature is discussed with emphasis on pathogenetic theories of dual sellar lesions. Although there is no direct evidence to confirm the pathogenetic relationship of collision sellar lesions, the number of cases presented in literature makes the theory of an incidental occurrence rather doubtful. Suggested hypotheses about a common embryonic origin or a potential interaction between pituitary adenomas and the immune system are presented

Double adenomas of the pituitary: an imaging, pathological, and clinical diagnostic challenge

Double and multiple adenomas of the pituitary are composed of two or more distinct tumors located in the same gland. They represent uncommon lesions measuring less than 1 cm, reported as having a low incidence in autopsies and occurring even more infrequently in surgical series. The histological diagnosis of double adenomas in surgical material is often extremely difficult, and confirmation requires immunohistochemistry and, occasionally, electron microscopy. Fragmented tissue material submitted for histology after transsphenoidal resection complicates the diagnosis. Difficulties in demonstrating double or multiple adenomas by imaging techniques contribute to diagnostic failure. Magnetic resonance imaging (MRI) techniques may disclose two separate adenomas located in the same pituitary gland. Intraoperative MRI and imaging ultrasonography, together with positron emission computed tomography, more accurately identify sites of residual tumors. These techniques might also detect postoperatively a residual tumor belonging to the second component of double adenoma. Double adenomas may also create extreme clinical diagnostic challenges. It is almost impossible to suspect functioning double adenomas with combined hormone secretion, each one secreting a different hormone, and distinguish them from an isolated plurihormonal adenoma, simultaneously secreting more than one hormone. Double adenomas may underlie surgical failure when one adenoma is removed while the other is left behind. Despite the low frequency of double adenomas, identification and resection of both of them is of major importance for the achievement of biochemical cure. © 2019, Hellenic Endocrine Society

Somatostatin receptor profile in pituitary thyrotroph adenomas

Objectives: Thyrotroph adenomas are the most infrequent adenohypophysial tumors. Somatostatin (SST) inhibits hormone secretion and suppresses cell proliferation. SST receptors (sstr) belong to a family of 5 types of G-coupled membrane proteins, which show high binding affinity to SST. Currently, SST analogs used to treat pituitary adenomas, have a preferential binding activity to sstr2 and sstr5. The aim of this study was to evaluate the status of all active sstrs on cell membrane of thyrotroph adenomas. Patients: Nine cases of thyrotroph adenomas were studied for all types of sstrs. All patients were clinically associated with hyperthyroidism. The adenomas were initially diagnosed and classified by histology and immunohistochemistry for all pituitary hormones and two of them were examined by electron microscopy. Methods: For sstr immunohistochemistry, antisera against all sst types (1, 2A, 2B, 3, 4 and 5) were used. To enhance sensitivity, the tyramide amplification technique was applied. This is the first report investigating the full spectrum of sstrs in thyrotroph adenomas by immunohistochemistry. Results: All tumors were immunoreactive for β-subunit of thyroid-stimulating hormone and for α-subunit of glycoprotein hormones. The sst2A, sst2B and sstr5 were co-expressed in all adenomas. The sstr1 and sstr3 were noted in 8 and sstr4 in 7 adenomas respectively. High scores 2+ and 3+ were prominent in sstr2A, sstr2B, sstr3 and sstr5. High score 3+ for sstr4 was also noted in one tumor, while score 3+ for sstr1 was not observed. Conclusions: Knowledge of the sstr status may contribute to a better selection of patients, anticipating benefit from treatment with SST analogs. Given that multiligand SST analogs have a broader ability to bind other sstrs, such as sstr1 and sstr3, patients with thyrotroph adenomas expressing these receptors may benefit from novel sstr targeting therapy. © 2020 Elsevier B.V

Is MGMT the best marker to predict response of temozolomide in aggressive pituitary tumors? Alternative markers and prospective treatment modalities

[No abstract available

Somatostatin receptor profile in pituitary thyrotroph adenomas

Objectives: Thyrotroph adenomas are the most infrequent adenohypophysial tumors. Somatostatin (SST) inhibits hormone secretion and suppresses cell proliferation. SST receptors (sstr) belong to a family of 5 types of G-coupled membrane proteins, which show high binding affinity to SST. Currently, SST analogs used to treat pituitary adenomas, have a preferential binding activity to sstr2 and sstr5. The aim of this study was to evaluate the status of all active sstrs on cell membrane of thyrotroph adenomas. Patients: Nine cases of thyrotroph adenomas were studied for all types of sstrs. All patients were clinically associated with hyperthyroidism. The adenomas were initially diagnosed and classified by histology and immunohistochemistry for all pituitary hormones and two of them were examined by electron microscopy. Methods: For sstr immunohistochemistry, antisera against all sst types (1, 2A, 2B, 3, 4 and 5) were used. To enhance sensitivity, the tyramide amplification technique was applied. This is the first report investigating the full spectrum of sstrs in thyrotroph adenomas by immunohistochemistry. Results: All tumors were immunoreactive for β-subunit of thyroid-stimulating hormone and for α-subunit of glycoprotein hormones. The sst2A, sst2B and sstr5 were co-expressed in all adenomas. The sstr1 and sstr3 were noted in 8 and sstr4 in 7 adenomas respectively. High scores 2+ and 3+ were prominent in sstr2A, sstr2B, sstr3 and sstr5. High score 3+ for sstr4 was also noted in one tumor, while score 3+ for sstr1 was not observed. Conclusions: Knowledge of the sstr status may contribute to a better selection of patients, anticipating benefit from treatment with SST analogs. Given that multiligand SST analogs have a broader ability to bind other sstrs, such as sstr1 and sstr3, patients with thyrotroph adenomas expressing these receptors may benefit from novel sstr targeting therapy. © 2020 Elsevier B.V

Is MGMT the best marker to predict response of temozolomide in aggressive pituitary tumors? Alternative markers and prospective treatment modalities

[No abstract available

Double adenomas of the pituitary: an imaging, pathological, and clinical diagnostic challenge

Double and multiple adenomas of the pituitary are composed of two or more distinct tumors located in the same gland. They represent uncommon lesions measuring less than 1 cm, reported as having a low incidence in autopsies and occurring even more infrequently in surgical series. The histological diagnosis of double adenomas in surgical material is often extremely difficult, and confirmation requires immunohistochemistry and, occasionally, electron microscopy. Fragmented tissue material submitted for histology after transsphenoidal resection complicates the diagnosis. Difficulties in demonstrating double or multiple adenomas by imaging techniques contribute to diagnostic failure. Magnetic resonance imaging (MRI) techniques may disclose two separate adenomas located in the same pituitary gland. Intraoperative MRI and imaging ultrasonography, together with positron emission computed tomography, more accurately identify sites of residual tumors. These techniques might also detect postoperatively a residual tumor belonging to the second component of double adenoma. Double adenomas may also create extreme clinical diagnostic challenges. It is almost impossible to suspect functioning double adenomas with combined hormone secretion, each one secreting a different hormone, and distinguish them from an isolated plurihormonal adenoma, simultaneously secreting more than one hormone. Double adenomas may underlie surgical failure when one adenoma is removed while the other is left behind. Despite the low frequency of double adenomas, identification and resection of both of them is of major importance for the achievement of biochemical cure. © 2019, Hellenic Endocrine Society

Small-Cell Malignancies of Thyroid: Challenge Solved?

"Small-cell malignancies of thyroid"is an unsolved dilemma. This term represents an umbrella terminology in thyroid, encompassing for a small group of tumors in which some of them are well-recognized tumors like medullary thyroid carcinoma, poorly differentiated thyroid carcinoma, and primary thyroid lymphomas and teratoma, whereas the remaining are less known as primary neuroendocrine carcinoma of thyroid, primary extraskeletal Ewing family tumors, and adamantinoma-like Ewing sarcoma. When the issue comes to evaluate a cytological sample predominantly composed of small-cell morphology, metastatic small-cell carcinomas to thyroid also should be excluded. In this review, our group focused on the main cytomorphological and clinical clues of each entity that help to set up a correct differential diagnosis. The literature discussions were also included for the entities that are not yet recognized by the mother publication WHO. A key point of the issue's simple algorithm based on FNAC with small-cell morphology of thyroid was suggested by the authors. © 2022 S. Karger AG, Basel. All rights reserved

Challenges in Cytology Specimens With Hürthle Cells

In fine-needle aspirations (FNA) of thyroid, Hürthle cells can be found in a broad spectrum of lesions, ranging from non-neoplastic conditions to aggressive malignant tumors. Recognize them morphologically, frequently represents a challenging for an adequately diagnosis and are associated with a significant interobserver variability. Although the limitations of the morphologic diagnosis still exist, the interpretation of the context where the cells appear and the recent advances in the molecular knowledge of Hürthle cells tumors are contributing for a more precise diagnosis. This review aims to describe the cytology aspects of all Hürthle cells neoplastic and non-neoplastic thyroid lesions, focusing on the differential diagnosis and reporting according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC). New entities according to the latest World Health Organization (WHO) classification are included, as well as an update of the current molecular data. © Copyright © 2021 Thodou, Canberk and Schmitt