Papillary thyroid carcinomas

Summary It is generally believed that the histological pattern of papillary thyroid carcinomas has no influence on the course of the disease. However, we were puzzled by the evident differences in the clinical course of these tumours and decided to re-examine all microscopic specimens available at the Institute of Pathology of the University of Zürich. These had been obtained from 169 surgical cases operated on between 1962 and 1977. We classified the material according to precise morphological criteria and matched it with a number of clinical and catamnestic data in order to determine which parameters correspond best with the development of the disease. Although the fate of patients below 50 years of age is slightly more favourable than that of older subjects, age is by no means the most important factor. In fact, the prognosis correlates significantly better with the initial local extension of the primary tumour (occult, intrathyroid or extrathyroid). Furthermore, this parameter is closely related to the histological pattern of our various papillary carcinoma subtypes which we graded according to differentiation. All factors considered, the morphological pattern appears to offer a rewarding approach to the provision of an accurate prognosis.     

Papillary thyroid carcinoma with anaplastic transformation showing a rhabdoid phenotype solely in the cervical lymph node metastasis

We describe a rare case of anaplastically transformed papillary thyroid carcinoma with a rhabdoid phenotype appearing solely in a metastatic focus. A 77-year-old man presented with a rapidly enlarging, painful right lateral cervical mass. CT scan revealed a tumor in the right upper pole of the thyroid gland and a right lateral cervical mass. Examination of surgically resected specimens disclosed that the thyroid tumor was a well-differentiated papillary carcinoma (2.0 cm in diameter), and the right lateral cervical mass was an anaplastic carcinoma (2.4 cm in diameter) showing a rhabdoid phenotype with scant amounts of a papillary carcinoma component in the periphery, considered to be transformed through the metastasis of the papillary thyroid carcinoma in a cervical lymph node. The rhabdoid cells had eccentric nuclei with conspicuous nucleoli and spherical hyaline cytoplasmic inclusions, which are immunoreactive for vimentin and sarcomeric actin. Ultrastructurally, these had globular aggregation of thin and intermediate filaments. Nuclear immunoreactivity for INI1 indicated that the tumor had no INI1 abnormalities, suggesting a secondary rhabdoid tumor. Recurrence developed in the right cervical and mediastinal lymph nodes, and the patient died of disease 6 months after surgery. A rhabdoid phenotype is a pathological hallmark indicating the aggressive nature not only in the neck region, but also in other organs.     

Papillary carcinoma of the thyroid with anaplastic transformation: diagnostic pitfalls in fine-needle aspiration biopsy

A case of coexistent papillary and anaplastic carcinoma of the thyroid is presented. The diagnosis of papillary carcinoma was made by fine-needle aspiration biopsy (FNAB); however, it did not correspond to the aggressive clinical behavior of the tumor. Subsequent biopsies revealed anaplastic carcinoma in the thyroid and pretracheal tissue. This case most likely represents anaplastic transformation in a pre-existing papillary carcinoma. The limitations of diagnosing this entity by FNAB as well as some possible solutions are discussed.     

Pancreatic metastasis of papillary thyroid carcinoma: a case report with review of the literature

In this article we give a case report on a PTC patient with pancreatic metastasis. In this case, the patient was admitted to our hospital for recurrence of PTC and occupying pancreatic lesions. We considered that the pancreatic neoplasm may be pancreatic metastasis of PTC but there is no previous experience about therapeutic approaches to this type of metastases. After some discussion the distant metastasis within the pancreas was successfully removed by a laparotomy and postoperative histology confirmed the diagnosis. After that surgery, the patient recovered well and then received total thyroidectomy and cervical lymph node dissection for recurrent thyroid cancer. After recovery he was discharged from hospital without further treatment. Eventually, he died of acute myocardial infarction in January 2010. To conclude, it is widely believed that the surgical operation should be chosen more positively in the management of those patients without multiple organ metastases. Thus on one hand it can serve to make a definite diagnosis, and on the other hand it can help the body get rid of the bulk of the tumor burden to prolong survival time of the patients.     

Papillary carcinoma of the thyroid with exuberant nodular fasciitis-like stroma

 We describe a rare case of papillary carcinoma with extensive proliferation of stromal cells. The stromal cells were immunocytochemically positive for vimentin, α-smooth muscle actin and desmin, but negative for cytokeratin, epithelial membrane antigen, S-100, thyroglobulin and CD34. These results and the ultrastructure of the stromal cells, which exhibited the characteristics of both fibroblasts and smooth muscle cells, indicated an origin from myofibroblasts. We conclude that myofibroblastic proliferation may contribute to the stromal response in the slow growth of the papillary carcinoma. Received: 29 August 1996 / 26 May 1997     

EGFR and CXCR1 expression in thyroid carcinoma in Qassim Region-Saudi Arabia: Correlation with clinicopathological parameters

AimsRecent evidence indicates an increased incidence of thyroid carcinoma, especially papillary thyroid carcinoma (PTC), in Saudi Arabia. EGFR and CXCR1 were reported to have increased expression in several human neoplasms. The goals of the present research was to investigate EGFR and CXCR1 expression in thyroid carcinoma and correlate the results to the established prognostic factors.MethodsImmunohistochemical study for both EGFR and CXCR1 was performed on formalin-fixed paraffin-embedded thyroid carcinomas tissues sections applying Labeled Streptavidin-biotin method (LSAB).ResultsRemarkable high expression of EGFR and CXCR1 were observed in PTC cases (56% and 63% respectively). There was association between EGFR expression in PTC and each of histologic subtype, lymph node metastasis (LNM), distant metastasis (DM), TNM staging and tumor relapse. There was statistical significant correlation between CXCR1 expression in PTC and each of histologic subtype, LNM, and tumor relapse. A significant correlation was detected between concomitant EGFR and CXCR expression and LNM, DM, increasing stage and tumor relapse.ConclusionsThe results of the present study demonstrated, a statistically positive correlation of EGFR and CXCR1 expression in PTC compared to normal thyroid tissues and nodular hyperplasia in Qassim Region- Saudi Arabia. Concomitant high expression of both receptors were strongly correlated with LNM, DM, TNM stage and tumor relapse than did each alone. These findings suggest that EGFR and CXCR1 play crucial roles in PTC and serve as predictors of poor prognosis, biomarkers of tumor diagnosis, and potential targets of cancer therapeutics.     

Papillary thyroid carcinoma presenting as a solitary soft tissue arm metastasis in an elderly hyperthyroid patient. Case report and review of the literature

A case of papillary thyroid carcinoma (PTC) presenting as a solitary metastasis in the right arm muscle is described in an elderly hyperthyroid male patient. A 2-cm nodule in the right bycipites muscle was found to be a papillary carcinoma of thyroid origin and a primary, 3.5-cm tumor was subsequently found in the left lobe of a hyperfunctioning gland due to toxic goiter. Both tumors were well differentiated PTC, follicular variant. No high grade features, nor extrathyroidal spread, nor regional lymph node metastases were found, but histology evidenced intrathyroidal vascular invasion. After radical surgery and radioiodine therapy, the patient is currently disease-free 4 years after diagnosis. This is the third reported case of PTC manifesting as a single soft tissue metastasis and the first associated with hyperthyroidism. Hematogenous spread of differentiated PTC is rare, although less unusual in PTC follicular variant. Histological vascular invasion, hypervascularity and increased blood flow in the hyperfunctioning thyroid gland might have facilitated the dissemination of malignant tumor cells through the bloodstream. Literature data indicate that PTC in elderly patients is increasing and is often clinically aggressive. Radical surgical and radiometabolic treatments are required also in this age group to improve clinical outcome.This work was partially supported by grants from the Italian Ministry of Education and University (ex 60% to MP).     

Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma

We describe two cases of papillary carcinoma of the thyroid containing prominent nodular, fasciitis-like stroma. In one of the cases infiltration into the adjacent parathyroid gland and metastases to two cervical lymph nodes occurred. In the lymph nodes and the parathyroid gland the carcinoma grew without any fasciitis-like stroma. This unusual change in tumour stroma seems to be reactive in nature and confined only to the thyroid and adjacent soft tissues.     

The many faces and mimics of papillary thyroid carcinoma

This article provides an overview of the 15 histologic variants of papillary thyroid carcinoma listed by the 2004 World Health Organization (WHO) monograph on endocrine tumors. The histologic features, differential diagnosis, and clinical course of each variant are discussed in some detail. The follicular variants (conventional and macrofollicular) constitute a morphologic challenge because the majority of these tumors are encapsulated and, also, because, in many tumors, not all neoplastic cells show the nuclear features considered to be diagnostic of papillary carcinoma. As a result, most of these tumors are missed even by experienced pathologists. Moreover, hyperplastic thyroid lesions, follicular adenomas, and Hashimoto’s thyroiditis may contain cells with clear nuclei resembling those of papillary carcinoma. Papillary carcinomas composed entirely of hyperchromatic cells have been overlooked. The WHO monograph defines papillary carcinoma with focal spindle and giant cell carcinoma components but its clinical behavior is unknown. Papillary carcinoma with an insular pattern that does not show the artifactual separation of the cell nests has been misinterpreted as the solid variant of papillary carcinoma. Papillary microcarcinomas include not only the conventional type and the follicular variants but also the tall cell and columnar cell variants.     

Apaf-1在甲状腺乳头状癌中的表达及意义

目的:探讨凋亡蛋白酶活化因子1(Apaf-1)在甲状腺乳头状癌(PTC)中的m RNA与蛋白表达及其与细胞增殖的关系。方法:分别采用real-time PCR、Western blot及免疫组化法检测并比较甲状腺乳头状癌和癌旁组织中Apaf-1的m RNA及蛋白表达情况,并分析其表达水平与PTC临床病理学特征的关系;通过下调CGTHW-3细胞中Apaf-1表达量,验证Apaf-1对细胞增殖的影响。结果:在PTC组织中,Apaf-1的m RNA和蛋白表达量均显著低于癌旁组织(P 0. 05);下调Apaf-1表达增强了CGTHW-3细胞的增殖活性(P 0. 05)。结论:Apaf-1在PTC中低表达,抑制其表达可增强CGTHW-3细胞的增殖能力。Apaf-1在甲状腺乳头状癌中可能发挥抑癌作用。     

Papillary thyroid carcinoma with metastasis to the frontal skull

Papillary thyroid carcinoma with metastasis to the frontal skull is extremely rare. We report a case of unsuspected papillary thyroid carcinoma with frontal skull metastasis. The patient was a 62‐year‐old African American woman with presentation of a 4‐cm firm, painless, immobile, ill‐defined mass at the right forehead. Ultrasound and computer tonography detected a hypervascular and osteolytic tumor involving the skull and overlying skin. Fine‐needle aspiration was performed followed by surgical biopsy. Cytologic examination revealed the presence of hypercellular and bloody material. The neoplasm showed glandular features and was composed of clusters of round to oval cells with pinkish squamoid cytoplasm, oval nuclei and inconspicuous nucleoli on smears and sections of cell block. With immunocytochemical stain, the neoplastic cells were positive for pancytokeratin and vimentin and focally positive for EMA, while they were negative for S100, HMB45, Melan‐A, CD34, GFAP, CD10, LCA, RCC and CD138. The diagnosis was a metastatic carcinoma. Clinical follow up with surgical biopsy was recommended. Surgical biopsy demonstrated histological and cytological features of papillary thyroid carcinoma including prominent papillae, nuclear overlapping, grooves, and intranuclear pseudoinclusions. Thus, a diagnosis of metastatic papillary thyroid carcinoma was rendered. Though skull metastasis of thyroid carcinoma is rare, it should be considered in the differential diagnosis when a skull mass lesion is encountered. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

甲状腺球蛋白测定与131I全身显像在甲状腺乳头癌复发监测中的意义

探讨甲状腺球蛋白(Tg)和131I全身显像(131I-WBS)在甲状腺乳头癌(PTC)复发监测中的意义. 30例PTC患者术后6周,行131I(3.7GBq)首次清除残留甲状腺组织治疗,6个月后再给予131I 治疗1次,治疗中同时测定Tg和进行131I-WBS.结果表明,在首次清除残留甲状腺组织治疗时,显像发现淋巴、肺及骨转移6例,其余转移灶于6个月治疗时发现,有3例患者(10%)Tg测定在正常范围,而131I-WBS出现转移灶,4例患者(13.3%)Tg测定异常,而131I-WBS正常.Tg测定和131I-WBS可作为诊断PTC有无转移的重要指标,二者监测复发应联合应用,可互相补充.     

Occult papillary carcinoma of the thyroid with pulmonary lymphangitic spread diagnosed by lung biopsy

Summary Distant metastases from occult papillary carcinoma of the thyroid, which is defined as a tumor less than 15 mm in diameter, are extremely rare. A 21-year-old patient with miliary micronodular densities in both lungs is described, in whom pulmonary lymphangitic spread of occult papillary thyroid carcinoma was diagnosed by thransthoracic lung biopsy.Abkürzungen BAL bronchoalveolar lavage - TBB transbronchial biopsy     

Papillary thyroid carcinoma with atypical histiocytoid cells on fine‐needle aspiration

Although papillary thyroid carcinoma (PTC) usually has classic cytological characteristics on fine‐needle aspiration (FNA), it can present rarely with aberrant features resembling those of histiocytes in a cystic nodule. The aim of the current study was to describe PTC with atypical histiocytoid cells and distinguish it from benign histiocytes. A retrospective computerized search for FNAs with atypical features suggestive of PTC and cystic degeneration was performed, and if available, the corresponding resection specimens were compared. Four cases met the criteria for FNAs and three had surgical pathology follow‐up, which showed PTC. One aspirate had some features typical of PTC, but the remaining FNAs had atypical histiocytoid cells, which had traits intermediate between those of PTC and histiocytes. Large cell size, pseudoinclusions, nuclear grooves, and multiple well‐defined vacuoles in atypical histiocytoid cells favor PTC over benign histiocytes. Ancillary immunocytochemical studies can also be useful in confirming the diagnosis. Histiocytic cells are frequently present in thyroid aspirates, and occasionally, they have atypical features that represent an unusual presentation of PTC. Closer examination of these cells can provide diagnostic clues for preventing false‐negative diagnosis of PTC. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin-fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.     

Correlation between calcification and bone sialoprotein and osteopontin in papillary thyroid carcinoma

The correlation between calcification and papillary thyroid carcinoma has received increasing attention. We investigated the ability of bone sialoprotein (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid carcinoma (PTC), and explored the correlation between BSP and OPN protein levels and calcification in PTC. Archival PTC specimens from patients with PTC with calcification and lateral cervical lymph node metastasis (LNM) were included in this retrospective immunohistochemical study. The protein levels of BSP and OPN were analysed immunohistochemically using routinely prepared tissue sections. PTC specimens from 66 patients with PTC were reviewed retrospectively (25 patients with histological calcification seen in paraffin sections, 41 patients without calcification; 35 patients with lateral cervical LNM, 31 patients without LNM). The percentage of samples that had cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules, and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%, respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a significant difference in the immunohistochemical score (IHS) for BSP and OPN protein staining between PTC specimens with and without calcification (P < 0.05). The level of BSP protein staining was found to be significantly correlated with the level of OPN protein staining in PTC specimens. We conclude that the strong correlation between BSP and OPN and PTC suggests a role for BSP and OPN in calcification and tumor progression of PTC. BSP and OPN might be useful tumour markers for the diagnosis of PTC with limited value, because both of them had low specificity.     

Renal-cell carcinoma with intranuclear inclusions metastatic to thyroid: a diagnostic problem in aspiration cytology

A case of renal-cell carcinoma (RCC) exhibiting prominent intranuclear inclusions in a metastasis to the thyroid is presented. RCC had been treated in this patient by right nephrectomy 7 yr earlier and by left partial nephrectomy 5 yr earlier; the patient had also received radiation to the neck 4 yr earlier for carcinoma in situ of the left true vocal cord. Aspiration performed on a rapidly enlarging mass in the left lobe of the thyroid revealed both clusters of tumor cells and single tumor cells with prominent intranuclear inclusions. Definitive distinction between a primary and metastatic neoplasm was difficult on the aspiration specimen. Subsequent thyroidectomy confirmed the diagnosis of metastatic renal-cell carcinoma with intranuclear inclusions by histologic, immunohistochemical, and ultrastructural analysis. The differential diagnosis by aspiration cytology of thyroid neoplasms that contain intranuclear inclusions is discussed.     

Papillary thyroid carcinoma metastatic to the pancreas: Case report

Papillary thyroid carcinoma (PTC) is generally associated with an excellent long‐term outcome. Distant metastasis is rare with only 5‐7% of patients developing distant disease. Metastasis of PTC to the pancreas is an exceedingly rare occurrence. To date, few cases have been reported. We present the case of an 81‐year‐old man with past medical history of PTC status post total thyroidectomy with local recurrence treated with radioactive iodine and selective neck dissection. Ten years after his initial diagnosis, PET‐CT scan revealed a new hypermetabolic 1.1 cm × 0.9 cm left lower lobe lung nodule and hypermetabolism in the proximal body of the pancreas. Follow‐up MRI cholangiogram showed a 1.0 × 0.8 cm T1 hypointense lesion in the proximal body of the pancreas. Endoscopic ultrasound‐guided fine‐needle aspiration biopsy of the pancreatic mass showed neoplastic epithelial cells arranged in papillary clusters with fibrovascular cores and syncytial sheets with high nuclear to cytoplasmic ratio, visible nucleoli, nuclear pallor, focal nuclear grooves, and rare intranuclear pseudoinclusions. Immunohistochemical stains performed on the smears showed positive nuclear expression of TTF‐1 and PAX‐8. The findings were consistent with metastatic PTC. Surgical resection of the lung nodule confirmed metastatic PTC. Pancreatic metastases usually occur after long time intervals with reports of up to 8 years in PTC. This makes the diagnosis more challenging, and metastatic disease should always be in the differential diagnosis in cases presenting with a pancreatic mass, especially in patients with a prior malignancy.