|
1
|
Rivera JP, Hang JF. Next-Generation Immunohistochemistry in Thyroid Neoplasm: A Practical Review on the Applications in Diagnosis and Molecular Classification. Endocr Pathol 2025; 36:8. [PMID: 40111709 PMCID: PMC11925991 DOI: 10.1007/s12022-025-09851-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/06/2025] [Indexed: 03/22/2025]
Abstract
An integrative histologic and molecular classification of thyroid tumors has become clinically relevant due to the potential role in risk stratification and selection of targeted therapy. In this review, we discuss the applications of six "next-generation" immunohistochemical markers, namely BRAF V600E (clone VE1), RAS Q61R (clone SP174), pan-TRK (clone EPR 17341), ALK (clones 5A4 or D5F3), PTEN, and β-catenin in the pathologic diagnosis and molecular classification of thyroid tumors. These biomarkers allow the in situ examination of tumor tissue and assist in the diagnosis and pathologic staging by highlighting tumor border and patterns of invasion, identifying isolated tumor cells in lymph nodes, distinguishing lymph node metastasis from benign intranodal thyroid inclusions, and diagnosing multicentric thyroid carcinomas with discordant molecular drivers. Furthermore, it can identify specific thyroid neoplasms that may occur sporadically or may be associated with hereditary syndromes. The next-generation immunohistochemistry provides a novel solution to challenging issues in thyroid pathology and fast turn-around time for accurate molecular classification and further guidance of therapeutic management.
Collapse
Affiliation(s)
- Jonathan P Rivera
- Department of Laboratories, Philippine General Hospital, Manila, Philippines
| | - Jen-Fan Hang
- Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Shipai Rd, No. 201, Sec. 2, Taipei, 11217, Taiwan.
- Department of Pathology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| |
Collapse
|
|
2
|
Benghashir H, Petkar M, Goyal R. Papillary Thyroid Carcinoma with Fibromatosis/Fasciitis-Like/Desmoid-Type Stroma: Case Report of a Rare Subtype with Cytological and Molecular Study. Head Neck Pathol 2024; 18:111. [PMID: 39436475 PMCID: PMC11496448 DOI: 10.1007/s12105-024-01720-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 10/04/2024] [Indexed: 10/23/2024]
Abstract
BACKGROUND Papillary thyroid carcinoma (PTC) with fibromatosis/fasciitis-like/desmoid-type stroma is a rare subtype of PTC,characterized by two distinct components: a classic papillary carcinoma component and a spindle cell proliferationresembling fibromatosis or nodular fasciitis. This stromal component adds a unique dimension to the tumor'spathology, making diagnosis more challenging and potentially leading to misclassification. CASE PRESENTATION We present a case of this rare entity which contributes to the growing body of literature by providing additionalmolecular data, which may shed light on the biological behaviour of the fibromatosis-like stroma and its relationshipwith the papillary carcinoma component. This case underscores the importance of recognizing this subtype, as itsspindle cell proliferation could be mistaken for a separate neoplasm or reactive process, resulting in inappropriatemanagement. CONCLUSIONS Increased awareness of this entity will help pathologists avoid diagnostic pitfalls and guide clinicians in developingmore precise treatment plans, addressing both the malignant papillary component and the unique stromal features.This case further enriches the current understanding of the heterogeneity of PTC and highlights the need fortailored management strategies in rare subtypes.
Collapse
Affiliation(s)
- Hosamadean Benghashir
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
| | - Mahir Petkar
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
| | - Rajen Goyal
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
| |
Collapse
|
|
3
|
Seko T, Kato H, Ando T, Kobayashi K, Shibata H, Ogawa T, Kawaguchi M, Noda Y, Hyodo F, Matsuo M. Thyroid hemiatrophy associated with papillary thyroid carcinoma. Neuroradiology 2024; 66:1795-1803. [PMID: 39136714 DOI: 10.1007/s00234-024-03442-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 08/01/2024] [Indexed: 09/26/2024]
Abstract
PURPOSE The present study aimed to investigate CT imaging features, pathological findings, and prognosis in patients with thyroid hemiatrophy (THA) associated with papillary thyroid carcinoma (PTC). METHODS This retrospective study included 225 patients with histopathologically proven PTC treated by surgical resection who underwent preoperative CT scanning. On CT images, THA was defined as thyroid parenchymal hemiatrophy on the ipsilateral side of PTC. CT findings, overall survival, and disease-free survival were compared between patients with and without THA. Pathological findings were also assessed in PTCs with and without THA. RESULTS THA was observed in 35 of 225 (16%) patients with PTC. Atrophic thyroid parenchyma was observed in the right lobe of 20 patients (57%) and in the left lobe of the remaining 15 patients (43%). With respect to the solid components within PTCs, contrast-enhanced CT attenuation (114.2 ± 18.2 vs. 126.7 ± 31.3 HU; p < 0.05) and CT attenuation change for contrast-enhanced CT minus unenhanced CT (60.2 ± 18.1 vs. 72.3 ± 31.0 HU; p < 0.05) were significantly lower in PTCs with THA than in those without THA. Histopathologically, almost all PTCs with THA (97%) had keloid-like collagen, which is broad bundles of hypocellular collagen with bright eosinophilic hyalinization, typically observed in keloid. However, no significant differences were observed in the prognosis between the two groups. CONCLUSION THA was occasionally observed in patients with PTC. Weak contrast-enhancement was distinct characteristic of PTC patients with THA, which is probably caused by keloid-like collagen.
Collapse
Affiliation(s)
- Takuya Seko
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Hiroki Kato
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.
| | - Tomohiro Ando
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| | | | | | - Takenori Ogawa
- Department of Otolaryngology, Gifu University, Gifu, Japan
| | - Masaya Kawaguchi
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| | - Yoshifumi Noda
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
- Department of Frontier Science for Imaging, Gifu University, Gifu, Japan
| | - Fuminori Hyodo
- Center for One Medicine Innovative Translational Research (COMIT), Institute for Advanced Study, Gifu University, Gifu, Japan
- Department of Pharmacology, School of Medicine, Gifu University, Gifu, Japan
| | - Masayuki Matsuo
- Department of Radiology, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan
| |
Collapse
|
|
4
|
Hu J, Wang F, Xue W, Jiang Y. Papillary thyroid carcinoma with nodular fasciitis-like stroma - an unusual variant with distinctive histopathology: A case report. World J Clin Cases 2023; 11:5797-5803. [PMID: 37727715 PMCID: PMC10506009 DOI: 10.12998/wjcc.v11.i24.5797] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 07/12/2023] [Accepted: 08/03/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Papillary thyroid carcinoma (PTC) is regarded as a fairly common endocrine malignancy, which can be divided into different multiple variants due to wide morphologic differences. The majority of PTC variants have been reported, but PTC with nodular fasciitis-like stroma (NFS) is a rare pathological variant and has been infrequently reported in the relevant literature. This condition involves abundant reactive stromal components rich in spindle cells, which may account for 60%-80% of the tumor along with a typical papillary carcinoma. CASE SUMMARY A 44-year-old man presented with a 4-mo history of a palpable mass over the anterior aspect of the left neck, the tumor demonstrated gradual enlargement but was painless during the 4 mo prior to discovery. Thyroid function test results were normal. Physical examination showed an enormous and firm nodular mass in the left lobe of the thyroid gland extending to the level of the hyoid bone. Ultrasonography of the neck revealed a well-defined heterogeneous lesion measuring around 5.0 cm × 4.0 cm with a hypoechoic complex nodule, decreased vascularity and speckles of microcalcification. The patient underwent left thyroidectomy with central compartment lymph node dissection. Final histopathological examination confirmed the diagnosis of PTC with extensive fibromatosis-like stroma combined with typical PTC. The patient was asymptomatic at the 3-mo follow-up. CONCLUSION PTC-NFS is a rare pathological variant and its diagnosis and prognosis may be similar to typical papillary carcinoma.
Collapse
Affiliation(s)
- Jun Hu
- Department of Thyroid Surgery, The First People’s Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China
| | - Fei Wang
- Department of Thyroid Surgery, The First People’s Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China
| | - Wei Xue
- Department of Thyroid Surgery, The First People’s Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China
| | - Yong Jiang
- Department of Thyroid Surgery, The First People’s Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China
| |
Collapse
|
|
5
|
Huang H, Li L, Liu X, Zhao L, Cui Z, Zhang R, Chen S. Papillary thyroid carcinoma with desmoid-type fibromatosis: the clinicopathological features with characteristic imaging and molecular correlation requiring comprehensive treatment. Hum Pathol 2023; 136:84-95. [PMID: 37019411 DOI: 10.1016/j.humpath.2023.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 03/18/2023] [Accepted: 03/30/2023] [Indexed: 04/05/2023]
Abstract
The pathogenesis and treatment of papillary thyroid cancer with desmoid-type fibromatosis (PTC-DTF), a rare subtype of papillary thyroid carcinoma characterized by a mixed epithelial-mesenchymal structure, are still ill-defined. Previous reports on PTC-DTF have had limited follow-up and recurrence has been rarely reported. To better understand this condition, we conducted a thorough analysis of five cases of PTC-DTF from our institute, including clinical and pathological examinations, imaging, immunohistochemistry, and molecular analysis. We also reviewed relevant literature. The mean age of the patients was 51.8 years, with three women and two men included in the group. Ultrasound often showed a hypoechogenic and well-defined nodule in the thyroid gland, except for one individual who had distant lung metastases detected by PET-CT. The nodules ranged in width from 0.5 to 5.0 cm and were excised in each case. Following surgery, 131I therapy was used in two cases. The overall number of PTC-DTF cases has risen from the previously reported 55 to 60, with females being the most commonly affected and ranging in age from 19 to 82. Most masses underwent a thyroidectomy, and approximately half of the patients had lymph node metastases. Histologically, PTC-DTFs were composed of a predominant stromal component (65% - 90%) and an intervening epithelial component. These spindle cells were arranged in parallel with abundant cytoplasm and vacuole-like nucleus but there wasn't evident atypia. The carcinoma cells were positively stained for CK and TTF-1 by immunohistochemistry, whereas mesenchymal cells were positive for SMA and displayed nuclear immunoreactivity for β-catenin. BRAF, NRAS, and CTNNB1 mutations were identified in the epithelial and mesenchymal components through molecular testing, respectively. Perhaps because the mesenchyme harbors aberrant nuclear β-catenin expression, PTC-DTF is more aggressive and prone to invasion and distant recurrence, as shown by our case 2, which is the first case to be reported thus far. PTC-DTF is typically treated with surgery, but clinicians may occasionally consider more holistic treatment plans that involve radioactive iodine and endocrine therapy.
Collapse
|
|
6
|
Juhlin CC, Hysek M, Stenman A, Zedenius J. Papillary Thyroid Carcinoma with Desmoid-Like Fibromatosis: Double Trouble? Endocr Pathol 2022; 33:525-527. [PMID: 36242758 PMCID: PMC9712337 DOI: 10.1007/s12022-022-09735-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/07/2022] [Indexed: 11/03/2022]
Affiliation(s)
- C Christofer Juhlin
- Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, 176 64, P1:02, Solna, Stockholm, Sweden.
| | - Martin Hysek
- Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, 176 64, P1:02, Solna, Stockholm, Sweden
| | - Adam Stenman
- Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden
| | - Jan Zedenius
- Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden
| |
Collapse
|
|
7
|
Shin E, Koo JS. Cell Component and Function of Tumor Microenvironment in Thyroid Cancer. Int J Mol Sci 2022; 23:ijms232012578. [PMID: 36293435 PMCID: PMC9604510 DOI: 10.3390/ijms232012578] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 10/17/2022] [Indexed: 11/16/2022] Open
Abstract
Thyroid cancer is the most common cancer in the endocrine system. Most thyroid cancers have good prognosis, but some of them are resistant to treatment or show aggressive behavior. Like other tumors, thyroid cancers harbor tumor microenvironment (TME) composed of cancer associated fibroblasts (CAF) and immune cells. Autoimmune lymphocytic thyroiditis can occur in the thyroid, and it may be associated with cancer development. TME is involved in tumor progression through various mechanisms: (1) CAF is involved in tumor progression through cell proliferation and extracellular matrix (ECM) remodeling; and (2) immune cells are involved in tumor progression through cell proliferation, angiogenesis, epithelial mesenchymal transformation (EMT), and immune suppression. These events are activated by various cytokines, chemokines, and metabolites secreted from cells that comprise TME. This review is focused on how CAF and immune cells, two important cell components of thyroid cancer TME, are involved in tumor progression, and will explore their potential as therapeutic targets.
Collapse
Affiliation(s)
| | - Ja Seung Koo
- Correspondence: ; Tel.: +82-2-2228-1772; Fax: +82-2-362-0860
| |
Collapse
|
|
8
|
Negură I, Ianole V, Dănilă R, Ungureanu MC, Apostol DGC. Primary solitary fibrous tumor of the thyroid gland: A review starting from a case report. Arch Clin Cases 2022; 8:97-105. [PMID: 34984233 PMCID: PMC8717007 DOI: 10.22551/2021.33.0804.10193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Primary solitary fibrous tumor (SFT) of the thyroid gland is a rare mesenchymal tumor with fibroblastic differentiation, ramified, thin-walled, enlarged (staghorn) vessels and specific NAB2-STAT6 gene fusion, which is more commonly found in pleura and peritoneum. This neoplasm can be located in a variety of anatomical sites outside pleura and peritoneum including bone, visceral organs and soft tissues, head and neck examples representing only 10-15% of the extra-pleural and extra-peritoneal tumors. Diagnosing this entity can be difficult, especially in thyroid gland, mainly because of the rarity of this neoplasm, but presence of characteristic microscopic features together with positivity for STAT6 and CD34 can confirm the diagnosis and exclude other differential diagnosis. Information about the diagnosis and treatment options of thyroid SFTs is limited but almost all primary thyroid SFTs have a good prognosis and indolent clinical course. Clinical surveillance is still necessary because some SFTs can be aggressive. Raising awareness regarding extra-pleural and extra-peritoneal location of this tumor in endocrine organs can help to better manage these patients. We report the case of a 34-year-old female with primary SFT of the thyroid gland. Additionally, we review the literature for the main clinical, paraclinical and pathological features of this neoplasm.
Collapse
Affiliation(s)
- Ion Negură
- Pathology Department, "Sf. Spiridon" Emergency County Clinical Hospital, Iasi, Romania.,Pathology Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Victor Ianole
- Pathology Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Radu Dănilă
- Department of Surgery, III-rd Surgical Unit, "Sf. Spiridon" Emergency County Clinical Hospital, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Maria-Christina Ungureanu
- Endocrinology Department, "Sf. Spiridon" Emergency County Clinical Hospital, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Delia Gabriela Ciobanu Apostol
- Pathology Department, "Sf. Spiridon" Emergency County Clinical Hospital, Iasi, Romania.,Pathology Department, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| |
Collapse
|
|
9
|
CTNNB1 mutations in papillary thyroid carcinoma with prominent myofibroblastic stromal component. Mod Pathol 2021; 34:2087-2088. [PMID: 33846546 DOI: 10.1038/s41379-021-00809-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/09/2021] [Accepted: 03/14/2021] [Indexed: 01/06/2023]
|
|
10
|
Roukain A, La Rosa S, Bongiovanni M, Nicod Lalonde M, Cristina V, Montemurro M, Cochet S, Luquain A, Kopp PA, Sykiotis GP. Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis: Review of Published Cases. Cancers (Basel) 2021; 13:cancers13174482. [PMID: 34503292 PMCID: PMC8430917 DOI: 10.3390/cancers13174482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 08/27/2021] [Indexed: 12/30/2022] Open
Abstract
Simple Summary Papillary thyroid cancer (PTC)-desmoid type fibromatosis (DTF) is one of the rarest variants of PTC. The diagnosis is histological, and detecting a mutation of CTNNB1 in the mesenchymal component is highly suggestive of PTC-DTF. The treatment is essentially surgical. We conducted a review of all cases of PTC-DTF found in the English literature and our aim is to describe patient’s characteristics, histology, immunohistochemistry and somatic mutations of every case. Abstract Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (BRAF-mutated) and another component of mesenchymal proliferation (CTNNB1-mutated). We conducted a literature review on PTC-DTF. In total, 31 articles were identified, that together reported on 54 patients. The mean age was 47 years, with a 2.2:1 female predominance. No ultrasound features were found to be helpful in differentiating PTC-DTF from other PTC variants. Of the 43 cases that reported histological details, 60% had locally infiltrative disease (T3b or T4). Around 48% had cervical lymph node metastases, but none had distant metastases. While PTC-DTF may be locally more aggressive than classic PTC, its overall behavior is similar and can include extrathyroidal extension and lymph node metastases, which may contain a stromal component and show extranodal invasion. The mainstay of treatment for PTC-DTF is surgery, and the DTF component is not expected to be sensitive to radioactive iodine. External radiotherapy, non-steroidal anti-inflammatory drugs, tyrosine kinase inhibitors and chemotherapy have also been used in selected cases. Due to the rarity of these tumors and the lack of specific treatment guidelines, management should be discussed in a multidisciplinary team.
Collapse
Affiliation(s)
- Abdallah Roukain
- Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.R.); (P.A.K.)
| | - Stefano La Rosa
- Institute of Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
| | | | - Marie Nicod Lalonde
- Service of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
| | - Valérie Cristina
- Service of Medical Oncology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (V.C.); (M.M.)
| | - Michael Montemurro
- Service of Medical Oncology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (V.C.); (M.M.)
| | - Stephane Cochet
- Centre de Chimiothérapie Anti-Cancéreuse CCAC SA, Av. Alexandre Vinet 19b, 1004 Lausanne, Switzerland;
| | | | - Peter A. Kopp
- Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.R.); (P.A.K.)
| | - Gerasimos P. Sykiotis
- Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.R.); (P.A.K.)
- Correspondence: ; Tel.: +41-21-3140595
| |
Collapse
|
|
11
|
Parkhi M, Chatterjee D, Bardia A, Kanaval AJ, Sood A, Saikia UN, Bansal N. Papillary thyroid carcinoma with nodular fasciitis-like stroma: a rare variant. AUTOPSY AND CASE REPORTS 2021; 11:e2021320. [PMID: 34458186 PMCID: PMC8387080 DOI: 10.4322/acr.2021.320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 07/09/2021] [Indexed: 12/03/2022] Open
Abstract
Papillary thyroid carcinoma with desmoid-type fibromatosis (PTC-DTF) or nodular fasciitis-like stroma (PTC-NFS) is a rare morphological variant of PTC with a favorable prognosis. There is a paucity of molecular data regarding this entity. We present the case of a 20-year-old female who presented with a palpable mass over the anterior aspect of the neck for the past 3–4 months, which was diagnosed as PTC-NFS. Ultrasonogram of the neck revealed a bulky left lobe of thyroid that contained a well-defined heterogenous lesion measuring around 24 × 26 × 36 mm with involvement of the adjacent isthmus. She underwent a total thyroidectomy with central compartment lymph node dissection. Histological examination revealed a biphasic tumor with epithelial and stromal components resembling nodular fasciitis. Two dissected lymph nodes showed metastasis of the epithelial component only. On immunohistochemistry, BRAF mutant protein expression was evident in the epithelial component only, while β-catenin was negative in both the components. The histopathological diagnosis of papillary thyroid carcinoma with nodular fasciitis-like stroma was offered. Sanger sequencing revealed a BRAFV600E (c.1799T>A, Val600Glu) mutation. Post-operatively, no residual tumor was detected on ultrasound and radioiodine scans. The patient was doing well at follow-up of 9 months. PTC-NFS/DTF is a histological variant of PTC with a favorable prognosis. Our index case was associated with the BRAF mutation, which was restricted to the epithelial component. Thorough sampling of the excised specimen is essential in order not to miss the epithelial component, which, in most reported cases (including ours) appears to be small.
Collapse
Affiliation(s)
- Mayur Parkhi
- Post Graduate Institute and Medical Education and Research, Department of Histopathology, Chandigarh, India
| | - Debajyoti Chatterjee
- Post Graduate Institute and Medical Education and Research, Department of Histopathology, Chandigarh, India
| | - Anand Bardia
- Post Graduate Institute and Medical Education and Research, Department of Histopathology, Chandigarh, India
| | - Anwin Joseph Kanaval
- Post Graduate Institute and Medical Education and Research, Department of Nuclear Medicine, Chandigarh, India
| | - Ashwani Sood
- Post Graduate Institute and Medical Education and Research, Department of Nuclear Medicine, Chandigarh, India
| | - Uma Nahar Saikia
- Post Graduate Institute and Medical Education and Research, Department of Histopathology, Chandigarh, India
| | - Naval Bansal
- Fortis Hospital, Department of Surgery, Mohali, Punjab, India
| |
Collapse
|
|
12
|
Kanematsu R, Hirokawa M, Tanaka A, Suzuki A, Higuchi M, Kuma S, Hayashi T, Miyauchi A. Evaluation of E-Cadherin and β-Catenin Immunoreactivity for Determining Undifferentiated Cells in Anaplastic Thyroid Carcinoma. Pathobiology 2021; 88:351-358. [PMID: 34237735 DOI: 10.1159/000516263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 03/31/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION An immunohistochemical study has occasionally been performed to diagnose anaplastic thyroid carcinoma (ATC). However, antibodies to confirm the undifferentiated nature of ATC have not yet been evaluated. The aim of this study was to evaluate E-cadherin and β-catenin expressions in immunoreactivity to determine undifferentiated carcinoma cells in the diagnosis of ATC. METHODS We immunohistochemically examined 29 ATCs, 30 poorly differentiated thyroid carcinomas (PDTCs), 22 well-differentiated thyroid carcinomas (WDTCs), and 3 squamous cell carcinomas. Antibodies for thyroid transcription factor-1 (TTF-1), paired-box gene 8 (PAX8), β-catenin, and E-cadherin were used. RESULTS All WDTCs tested positive for TTF-1, PAX8, and E-cadherin. The positive rates of TTF-1, PAX8, and E-cadherin were 93.3, 93.3, and 100%, respectively, in PDTCs and 17.2, 51.7, and 10.3%, respectively, in ATCs. WDTC expressed the lateral cell membrane staining for β-catenin and E-cadherin, whereas PDTC showed circumferential cell membranous expression (fishnet pattern). β-catenin cell membrane expression in ATCs is lost or discontinuous. Carcinoma cells with β-catenin nuclear expression without cell membranous expression were scattered in 72.4% of ATCs but were not observed in the other carcinomas. CONCLUSION We propose 3 immunohistochemical findings to determine undifferentiated carcinoma cells in the diagnosis of ATC: (1) β-catenin nuclear expression with no or reduced cell membranous expression, (2) the loss or discontinuous pattern of E-cadherin expression, and (3) the loss of PAX8 nuclear expression.
Collapse
Affiliation(s)
- Risa Kanematsu
- Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan
| | | | - Aki Tanaka
- Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan
| | - Ayana Suzuki
- Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan
| | - Miyoko Higuchi
- Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan
| | - Seiji Kuma
- Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan
| | - Toshitetsu Hayashi
- Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan
| | | |
Collapse
|
|
13
|
Papillary thyroid carcinoma with prominent myofibroblastic stromal component: clinicopathologic, immunohistochemical and next-generation sequencing study of seven cases. Mod Pathol 2020; 33:1702-1711. [PMID: 32291398 DOI: 10.1038/s41379-020-0539-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 02/04/2023]
Abstract
Papillary thyroid carcinoma with desmoid-type fibromatosis or nodular fasciitis-like stroma is an extremely unusual and poorly understood subtype of papillary thyroid cancer. Although prior studies have demonstrated alterations in the Wnt/β-catenin signaling pathway in some of these tumors, controversy still exists regarding the nature of the stromal spindle component. We have studied seven cases of papillary thyroid carcinoma with prominent myofibroblastic stroma, including six men and one woman aged 20-65 years (mean age = 44). All cases displayed areas consistent with conventional papillary thyroid carcinoma embedded in abundant myofibroblastic-like stroma. The myofibroblastic stroma in six cases resembled desmoid-type fibromatosis and in one case it more closely resembled nodular fasciitis. By immunohistochemical staining, the stromal spindle component showed positivity for SMA and low MIB1 proliferation index in all cases, and there was at least patchy strong nuclear positivity for beta-catenin in six/seven cases. Stains for cytokeratin AE1/AE3 and PAX8 were positive in the epithelial elements but negative in the stromal component. Next-generation sequencing was performed on six of seven cases. CTNNB1 gene mutations were identified in six/seven cases. The epithelial component showed BRAF mutations in two cases and an NRAS mutation in one case. The case with fasciitis-like stroma was negative for beta-catenin by sequencing and immunostaining as well as negative for USP6 gene rearrangement. Our findings indicate that papillary thyroid carcinoma with prominent myofibroblastic stroma may represent more than one category of lesions.
Collapse
|
|
14
|
Cho YA, Oh YL. Case of medullary thyroid carcinoma with desmoid-type fibromatosis. Pathol Int 2020; 70:364-369. [PMID: 32249519 DOI: 10.1111/pin.12926] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 03/14/2020] [Accepted: 03/17/2020] [Indexed: 12/20/2022]
Abstract
A 36-year-old man was admitted to hospital for a right thyroid nodule incidentally discovered on a chest computed tomography scan for a rib fracture. He had no history of radiation to the head and neck, no known family history of endocrine disease, and no medical or surgical history. A 17 × 10 mm, well-demarcated, multinodular, whitish nodule with neither necrosis nor hemorrhage was found in the right thyroid. Microscopically, the tumor consisted of epithelial cell nests with oval, plasmacytoid or polygonal cells with speckled chromatin, inconspicuous nucleoli and granular cytoplasm. The surrounding stroma showed amyloid deposition and prominent spindle cell proliferation with myxoid substance. Epithelial cell nests showed an immunoreactive pattern for typical medullary thyroid carcinoma (MTC), and the spindle cell stroma showed nuclear expression of beta-catenin. This may be the first report on histopathologic findings of MTC with desmoid-type fibromatosis. Further studies are necessary to discover the clinicopathologic characteristics and pathogenesis of this rare type of tumor.
Collapse
Affiliation(s)
- Yoon Ah Cho
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Lyun Oh
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
15
|
Nishino M, Jacob J. Invasion in thyroid cancer: Controversies and best practices. Semin Diagn Pathol 2020; 37:219-227. [PMID: 32173146 DOI: 10.1053/j.semdp.2020.02.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 02/27/2020] [Indexed: 11/11/2022]
Abstract
Invasion is a key feature of malignancy and an important element in the classification, risk-stratification, and staging of thyroid cancers. However, the histopathologic criteria for tumor capsular invasion, angioinvasion, and extrathyroidal extension (ETE) have varied among pathologists, both in practice as well as in studies assessing the clinical significance of these findings. In this review, we provide historic context for the controversies surrounding the definition of invasion in thyroid neoplasms and highlight recent efforts to standardize how pathologists report capsular invasion, angioinvasion, and ETE. We offer practical suggestions for distinguishing invasion from its mimics and provide an algorithmic approach for classifying thyroid tumors based on integration of tumor invasiveness, nuclear atypia, and architectural pattern.
Collapse
Affiliation(s)
- Michiya Nishino
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, United States.
| | - Jack Jacob
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, United States
| |
Collapse
|
|
16
|
Roth EM, Barrows CE, Nishino M, Sacks B, Hasselgren PO, James BC. Papillary thyroid cancer with extrathyroidal extension of desmoid-type fibromatosis. A case report of an aggressive presentation of an uncommon pathologic entity. Int J Surg Case Rep 2019; 63:5-9. [PMID: 31499326 PMCID: PMC6734537 DOI: 10.1016/j.ijscr.2019.08.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 07/16/2019] [Accepted: 08/02/2019] [Indexed: 01/19/2023] Open
Abstract
INTRODUCTION Papillary thyroid cancer with desmoid-type fibromatosis (PTC-DTF) is an uncommon tumor characterized by extensive stromal proliferation of fibroblasts and myofibroblasts with a small component of PTC. We report a case of PTC-DTF with infiltration of the mesenchymal component of tumor into perithyroidal muscle and early recurrence of desmoid after thyroidectomy, an outcome previously not reported. PRESENTATION OF CASE A 20-year-old man underwent left hemithyroidectomy for a thyroid nodule. Pathology demonstrated a 4.2 cm tumor with PTC-DTF with the PTC comprising <10% of the tumor. The stromal component extended into adjacent skeletal muscle. After completion thyroidectomy, histopathology of the right thyroid lobe revealed no malignancy or fibromatosis. Neck MRI 16 months after the initial operation revealed a 10.5 cm tumor in the left thyroid bed. Core biopsy and open excisional biopsy showed desmoid-type fibromatosis without PTC. The patient is undergoing chemotherapy of his recurrent desmoid-type fibromatosis. DISCUSSION In patients with PTC-DTF there is a risk of recurrence of the benign component of the tumor. In recent reports, the role of less aggressive surgery, or even non-surgical management, of patients with recurrent DTF has been emphasized, in particular when extensive surgery may be associated with high risk of functional loss. The management of our patient adheres to modern recommendations for the treatment of DTF. CONCLUSION Patients with PTC-DTF should be carefully monitored after thyroidectomy for both recurrent PTC and local recurrence of the fibrous component of the tumor.
Collapse
Affiliation(s)
- Eve M Roth
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Courtney E Barrows
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Michiya Nishino
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Barry Sacks
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Per-Olof Hasselgren
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
| | - Benjamin C James
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| |
Collapse
|
|
17
|
Wong SBJ, Nga ME, Michal M, Vanecek T, Seet JE, Petersson F. SOX11 expression in a case of papillary thyroid carcinoma with fibromatosis/fasciitis-like stroma containing BRAF c.1799_1801delTGA and CTNNB1 c.133T>C mutations. Virchows Arch 2019; 475:519-525. [PMID: 31327063 DOI: 10.1007/s00428-019-02619-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 06/06/2019] [Accepted: 07/09/2019] [Indexed: 10/26/2022]
Abstract
We describe a case of papillary thyroid carcinoma with fibromatosis/fasciitis-like stroma (PTC-FLS) that contained the rare BRAF c.1799_1801delTGA (p.V600_K601delinsE) mutation, which has not previously been reported in this tumour, as well as the CTNNB1 c.133T>C (p.S45P) mutation. We also report the novel observation that spindle cells of the mesenchymal component exhibit diffuse nuclear but not cytoplasmic expression of SOX11, whereas the malignant epithelial cells did not. This suggests that immunoreactivity for SOX11 can be an alternative diagnostic tool for evaluating cases of PTC-FLS where the nuclear expression of β-catenin is ambiguous.
Collapse
Affiliation(s)
- Soon Boon Justin Wong
- Department of Pathology, National University Hospital, Singapore, Singapore.,Department of Microbiology and Immunology, National University of Singapore, Singapore, Singapore
| | - Min En Nga
- Department of Pathology, National University Hospital, Singapore, Singapore
| | - Michal Michal
- Department of Pathology, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic
| | - Tomas Vanecek
- Molecular and Genetic Laboratory, Biopticka Laboratory Ltd., Plzen, Czech Republic
| | - Ju Ee Seet
- Department of Pathology, National University Health System, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore
| | - Fredrik Petersson
- Department of Pathology, National University Hospital, Singapore, Singapore. .,Department of Pathology, National University Health System, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.
| |
Collapse
|
|
18
|
Thompson LDR, Wei C, Rooper LM, Lau SK. Thyroid Gland Solitary Fibrous Tumor: Report of 3 Cases and a Comprehensive Review of the Literature. Head Neck Pathol 2019; 13:597-605. [PMID: 30758754 PMCID: PMC6854167 DOI: 10.1007/s12105-019-01012-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 01/14/2019] [Indexed: 02/07/2023]
Abstract
Solitary fibrous tumors of the thyroid gland are exceptionally rare. In order to further characterize the clinical and pathologic features of solitary fibrous tumor arising at this anatomic site, three cases of thyroid gland solitary fibrous tumor were analyzed in conjunction with 35 cases compiled from the English literature. Thyroid gland solitary fibrous tumors showed an equal sex distribution with a mean age at presentation of 54.4 years (range, 28-88 years). The patients typically presented with an asymptomatic, slow growing neck mass. Microscopically, the tumors were characterized by cytologically bland spindle cells with patternless growth, hypocellular and hypercellular areas, variable amounts of collagen, and ectatic, branching blood vessels. Two previous reported tumors were considered to be histologically malignant on the basis of increased mitotic activity, profound pleomorphism and tumor necrosis. Immunohistochemically, the tumor cells are variably positive with CD34, bcl-2, and CD99. STAT6 immunohistochemistry, performed on the current cases, demonstrated a strong, diffuse nuclear expression in all tumors. Among 26 patients with available follow up data (mean 47.3 months), one developed local recurrence and distant metastasis. Solitary fibrous tumors occurring in the thyroid gland are uncommon, but can be reliably diagnosed based on the presence of characteristic morphologic features as well as immunohistochemical expression of STAT6 and CD34. The majority of thyroid gland solitary fibrous tumors have exhibited an indolent clinical course, however experience is limited. The rare potential for aggressive clinical behavior requires clinical surveillance.
Collapse
Affiliation(s)
- Lester D. R. Thompson
- Southern California Permanente Medical Group, Department of Pathology, Woodland Hills Medical Center, 5601 De Soto Avenue, Woodland Hills, Los Angeles, CA 91365 US
| | - Christina Wei
- Southern California Permanente Medical Group, Department of Pathology, Woodland Hills Medical Center, 5601 De Soto Avenue, Woodland Hills, Los Angeles, CA 91365 US
| | - Lisa M. Rooper
- Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD US
| | - Sean K. Lau
- Southern California Permanente Medical Group, Department of Pathology, Orange County-Anaheim Medical Center, Anaheim, CA US
| |
Collapse
|
|
19
|
Tajiri K, Hirokawa M, Suzuki A, Takada N, Ota H, Oshita M, Fukushima M, Kobayashi K, Miyauchi A. Can Ultrasound Alone Predict Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis? A Retrospective Analysis of 13 Cases, Focusing on the Stromal Area. Ultrasound Int Open 2018; 4:E39-E44. [PMID: 30250939 PMCID: PMC6148316 DOI: 10.1055/a-0591-6163] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 02/21/2018] [Accepted: 03/05/2018] [Indexed: 11/27/2022] Open
Abstract
Purpose Papillary thyroid carcinoma with desmoid-type fibromatosis (PTC-DTF) is extremely rare. So far, only 4 cases describing the ultrasound findings of this variant have been reported. Here, we describe the ultrasound findings of 13 cases of PTC-DTF, focusing especially on the DTF area. Materials and Methods We retrospectively analyzed the clinical reports, ultrasound reports, and ultrasound photographs obtained from medical records at Kuma Hospital. Results The patients included 8 women and 5 men with a mean age of 47.9 years. The widest dimension of the nodules ranged from 16 to 79 mm (mean: 37.5 mm). The original ultrasound reports classified the nodules as either intermediate suspicion or high suspicion. A diagnosis of PTC was suspected in 12 nodules, and anaplastic carcinoma was suspected in 1 nodule. PTC-DTF presented with an irregularly shaped nodule (100%), taller-than-wide sign (84.6%), heterogeneous echogenicity (100%), no microcalcification (76.9%), and no or mild flow signal on Doppler (75.0%). The DTF area was identified in the ultrasound photographs of 8 nodules. DTF areas were generally heterogeneous (62.5%) and more hypoechoic (71.4%) than PTC areas. Microcalcification was not observed in the DTF areas. All of the DTF areas revealed no or mild flow signal. On ultrasound elastography, the DTF areas were not stiff, and they were more elastic than the PTC areas. Conclusion It is difficult to predict PTC-DTF using ultrasound alone, and B-mode ultrasonography is more reliable than ultrasound elastography in the ultrasound diagnosis of malignant thyroid nodules.
Collapse
Affiliation(s)
- Kumiko Tajiri
- Kuma Hospital, Department of Clinical Laboratory, Kobe, Japan
| | | | - Ayana Suzuki
- Kuma Hospital, Department of Clinical Laboratory, Kobe, Japan
| | - Nami Takada
- Kuma Hospital, Department of Clinical Laboratory, Kobe, Japan
| | - Hisashi Ota
- Kuma Hospital, Department of Clinical Laboratory, Kobe, Japan
| | - Maki Oshita
- Kuma Hospital, Department of Clinical Laboratory, Kobe, Japan
| | | | | | | |
Collapse
|