Fine-needle aspiration cytology of papillary Hürthle cell carcinoma with lymphocytic stroma “Warthin-like tumor” of the thyroid

Papillary Hürthle cell carcinoma with lymphocytic stroma is a recent addition to the list of variants of papillary carcinoma of the thyroid. We report the aspiration cytology and histology findings of this tumor arising in two patients. The smears were cellular, and revealed Hürthle cells arranged in three-dimensional groups, papillary fragments, and as singly dispersed cells with a prominent intimately associated inflammatory component of lymphocytes and few plasma cells. The Hürthle cells were pleomorphic and showed granular eosinophilic cytoplasm, eccentrically oriented nuclei with prominent nucleoli. Nuclear features of papillary carcinoma were present among both the cellular groups and scattered cells. The histologic examination showed a circumscribed papillary tumor comprising Hürthle cells and a brisk inflammatory component filling the stalks of papillae. These findings were consistent with a papillary Hürthle cells carcinoma with lymphocytic stroma, the so-called Warthin-like tumor of the thyroid. Hürthle cells admixed with inflammatory cells in cytology preparations can be seen in Hürthle cell nodules or neoplasms arising in a background of chronic lymphocytic thyroiditis. We suggest that a careful search for nuclear features may be helpful in diagnosing this variant of papillary carcinoma.     

Diagnostic criteria in well-differentiated thyroid carcinomas

The criteria used for the differential diagnosis of well-differentiated thyroid tumors derived from follicular cells are reviewed taking into account the architectural characteristics together with the immunohistochemical and molecular features. The review is focused on follicular carcinoma, papillary carcinoma, follicular variant of papillary carcinoma, and oncocytic (Hürthle cell) tumors, as well as on the recently described borderline lesions: follicular and well-differentiated tumors of uncertain malignant potential, and well-differentiated carcinoma, not otherwise specified.     

桥本甲状腺炎伴不典型细胞与乳头状癌的鉴别诊断

目的：探讨桥本甲状腺炎伴不典型细胞与甲状腺乳头状癌( papillary thyroid carcinoma,PTC)的鉴别诊断。方法收集桥本甲状腺炎153例,分为桥本甲状腺炎伴不典型细胞组(32例)、桥本甲状腺炎伴PTC组(49例)、桥本甲状腺炎对照组(72例)。采用HE及免疫组化法分析各组间的差异。结果桥本甲状腺炎伴不典型细胞与PTC有形态学差异。伴PTC组Galec-tin-3、CK19阳性率高于伴不典型细胞组,CD56阳性率低于伴不典型细胞组,差异均有统计学意义。 Ki-67阳性率在伴不典型细胞组与伴PTC组之间差异无显著性,但与对照组之间差异有统计学意义。结论以组织形态学特征为基础,联合应用CD56、CK19、Galectin-3、Ki-67可有效鉴别桥本甲状腺炎伴不典型细胞与PTC。     

Distinguishing tall cell variant of papillary thyroid carcinoma from usual variant of papillary thyroid carcinoma in cytologic specimens

Tall cell variant (TCV) is an aggressive form of papillary thyroid carcinoma (PTC), usually associated with higher local recurrence and distant metastasis. Some authors have suggested that TCV can be effectively diagnosed on thyroid fine-needle aspiration (FNA); this diagnosis may help clinicians plan a more effective treatment regimen. The objective of this study was to compare the FNA specimens of TCV with those of usual variant of PTC (UV-PTC) and to define a set of distinguishing cytologic features. Thirty FNA specimens of histologically proven TCV were compared with 32 FNA specimens of histologically proven UV-PTC. All specimens were evaluated for the following features: papillary groups (PG), elongated/tall cells (EL/TC), oncocytic cytoplasm (OC), distinct cell borders (DCB), prominent central nucleoli (PCN), intranuclear grooves (NG), and intranuclear inclusions (NI). These features were semiquantitatively measured on a sliding scale of 0-4 in both air-dried Diff-Quik-stained and ethanol-fixed Papanicolaou-stained preparations. TCV showed distinctive cytologic features, which can distinguish them from UV-PTC. These included EL/TC, OC, and DCB and were also found to be statistically significant (P < 0.0001). No significant differences were noted for PG and NG. The NIs in TCV cases were qualitatively different than those in UV-PTC. In TCV there were multiple inclusions within the same nucleus imparting a "soap bubble appearance" to the nucleus. This feature was seen in almost all cases of TCV and was rarely seen in usual PTC. On the basis of the above-mentioned cytologic features, TCV can be distinguished from usual PTC in FNA specimens.     

Coexistence of primary squamous cell carcinoma of thyroid with classic papillary thyroid carcinoma

Primary squamous cell carcinoma of the thyroid gland is very rare and its histogenesis is poorly defined so far. Although there have been some cases of squamous cell carcinoma with variant types of papillary thyroid carcinoma (PTC), the present case is the first primary squamous cell carcinoma with classic PTC to be reported. A 43‐year‐old woman presented with a 20 year history of neck mass. Neck ultrasound indicated a 6 × 4 × 3 cm large mass. The patient underwent total thyroidectomy. Histopathology indicated a well‐differentiated squamous cell carcinoma and squamous metaplasia in conjunction with classic PTC. On immunohistochemistry cytokeratin 7 was positive in papillary carcinoma and squamous metaplasia, thyroglobulin was positive only in papillary carcinoma, and p63 was positive in squamous metaplasia and squamous cell carcinoma. Postoperatively, the patient received 59.4 Gy adjuvant radiotherapy, hormonal therapy and radioactive iodine therapy. At 8 months after surgery the patient remained disease free.     

Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma

The accurate diagnosis of differentiated thyroid tumors is very important for clinical management of patients. The histopathological distinction between some types of differentiated thyroid tumors can be very difficult even for experienced pathologists. We used immunohistochemical markers from published data obtained from DNA expression profiling, tissue microarray analysis, and immunohistochemistry to analyze a series of 157 thyroid tumors and 5 normal thyroids. These analyses showed that several antibodies were useful in distinguishing follicular adenomas from follicular variant of papillary thyroid carcinomas including HBME-1, CITED 1, galectin-3, cytokeratin 19, and S100A4 (p<0.0001). A combination of markers consisting of a panel of HBME-1, galectin-3, and CK19 or a panel of HBME-1, CITED1, and galectin-3 was usually most effective in distinguishing follicular adenoma from follicular variant of papillary thyroid carcinoma. Because individual tumors may not express some of these markers, the use of a panel of antibodies is recommended. These results indicate that some individual antibodies or a panel of antibodies combined with histopathological analysis can be useful in separating follicular adenoma (FA) from follicular variant of papillary thyroid carcinoma (FVPTC).     

Intranodal benign thyroid tissue: significance of HBME-1 in differentiation from metastatic papillary thyroid carcinoma

The aim of this study was to determine the significance of HBME-1 immunostaining in the differentiation between intranodal benign thyroid tissue and metastatic papillary thyroid carcinoma in the lymph node. Immunohistochemically we examined normal-appearing intranodal thyroid tissue in four patients who did not show evidence of papillary carcinoma histologically or clinically. We also examined follicular-pattern-predominant papillary carcinoma with metastatic foci in the lymph nodes. Normal-appearing intranodal thyroid tissue and normal thyroid showed no immunopositivity for HBME-1. In contrast, all papillary carcinomas in both the lymph nodes and thyroid demonstrated strong positivity for HBME-1. HBME-1 was predominantly positive for the luminal surface of the tumor cells. The immunopositivity of the cuboidal and low columnar carcinoma cells was more intensive than that of the flat-shaped cells in the lymph nodes and thyroid. The results probably indicate that HBME-1 immunostaining is helpful in distinguishing between intranodal benign thyroid tissue and metastatic papillary carcinoma in lymph nodes. We emphasize that the HBME-1 reactivity should be evaluated in connection with the histological findings, and that positive and negative controls stained in parallel are necessary.     

细胞角蛋白和Ret蛋白在甲状腺乳头状癌中的表达

目的　探讨甲状腺乳头状癌中细胞角蛋白 (CK)和ret的表达及其在病理诊断中的价值。方法　分别采用免疫组织化学EnVision法及LSAB法检测CK19、CK17、CK8、CK2 0及ret在 6 9例甲状腺乳头状癌、14例结节性甲状腺肿和 4 2例癌旁正常滤泡中的表达。结果　CK19、ret在乳头状癌组织的阳性率 (85 5 %、6 8 1% )明显高于结节性甲状腺肿和正常滤泡组织阳性率 (2 5 0 %、5 4 % ) ,二者差异有统计学意义 (P <0 0 1)。CK17在乳头状癌中有少量表达 (15 9% ) ,主要集中在鳞化及分化差或小灶浸润区域。分别有 75 4 %及 2 6 8%的乳头状癌及良性区域CK8染色阳性 ,所有病例CK2 0阴性。结论　CK19、CK17及ret在甲状腺乳头状癌中表达增加 ,在病理诊断中有一定价值。     

Columnar cell variant of papillary thyroid carcinoma: A diagnostic dilemma in fine‐needle aspiration cytology

Columnar cell variant of papillary thyroid carcinoma (PTC) is an uncommon variant with an aggressive course as compared to classic papillary carcinoma. Cytologic diagnosis of these tumors is difficult due to absence of characteristic nuclear features of classic pattern of papillary carcinoma. We present a case of columnar cell variant in a young female misdiagnosed on aspiration cytology. A 21‐year‐old female presented with solitary nodule in the left aspect of thyroid. A diagnosis of medullary thyroid carcinoma was rendered. The resected thyoroidectomy specimen revealed a columnar cell variant of PTC which was further supported by immunohistochemical staining. Diagn. Cytopathol. 2016;44:816–819. © 2016 Wiley Periodicals, Inc.     

Prevalence and prognostic significance of tall cell variant of papillary thyroid carcinoma

The aim of this study was to assess the prevalence, prognostic factors, and long-term outcome of tall cell variant (TCV) in comparison with the conventional forms of papillary thyroid carcinoma (PTC). A total of 945 patients with thyroid cancer were treated and followed up from 1960 to 1998. Pathologic review was performed in 778 patients (84%) of the cohort. Of these, 674 had PTC: 503 (74%) had conventional form (CF); 56 (8%), TCV; and 155 (17%), other variants of PTC. Tall cell variant was associated with tumors of larger size (P < .001), bilaterality (P < .02), multifocality (P < .04), and extrathyroidal invasion (P < .001). Treatment was similar in both groups, but neck dissection was performed more frequently in patients with TCV (P < .04). The 10-year overall and event-free survival rates were, respectively, 90% and 85% in the CF versus 79% and 67% in the TCV group (P < .001). Histologic subtype did not have an effect on clinical outcome after multivariate analysis, the most relevant factors being age, involved nodes, or the "Metastasis, Age, Completeness, Invasion, Size" classification after multivariate analysis. In this large cohort of patients, TCV represents 8.3% of PTC, and it is a more aggressive form of PTC than CF because of the higher stage and increased grade.     

Thyroid papillary carcinoma arising in ectopic thyroid tissue within a branchial cleft cyst

A case of papillary carcinoma arising in ectopic thyroid tissue within a branchial cleft cyst is described. A 46-year-old woman presented with a 2.0 x 2.0 cm mass in her left lateral neck. The excised mass showed a cystic lesion with a thyroid papillary carcinoma. Following a lateral cervical cystectomy, subsequent thyroid gland and lymph nodes dissections were performed. Pathological examination showed an adenomatous goiter and no primary carcinoma in the thyroid gland, as well as metastatic papillary carcinoma in the lymph nodes. Two cases of thyroid papillary carcinoma arising in ectopic thyroid tissue within a branchial cyst have been reported previously, but no lymph node metastases were recognized. The first case of papillary carcinoma arising in ectopic thyroid tissue within a branchial cleft cyst, and accompanied by lymph node metastasis is presented.     

Patterns of papillary thyroid carcinoma cells analyzed in fine-needle aspiration smears may reveal changes in tumor cell behavior

Fine-needle aspiration (FNA) cytology is widely used to examine thyroid lesions. However, its diagnostic accuracy is limited by the narrow choice of cytopathologic markers indicative of invasive/metastatic powers of a tumor. The aim of this study was to identify features that may serve as such indicators. We have examined FNA smears of 50 histologically proven papillary thyroid carcinoma (PTC) cases applying computer-assisted morphometry to assess patterns formed by PTC cells. Cytokeratine (CK) 8 immunocytochemistry was used to verify the epithelial origin of cells under study. All analyzed smears contained blood, histiocyte-like cells and CK8-positive follicular cells occurring both as single cells and in monolayer cell sheets. In 60% of cases we revealed cell sheets displaying two distinct cell patterns. The first one (pattern R) consisted of moderately pleomorphic, rather regularly arranged cells having an amphophilic cytoplasm. The second one (pattern I) was formed by highly pleomorphic cells with a basophilic cytoplasm. Patterns R and I were clearly different in cell size and shape as well as in nuclear size and shape. These patterns were never observed within the same cell sheet indicating that they may be formed by different subclones of tumor cells. Thus, it can be concluded that PTC frequently displays two definitely different cell patterns. We think that these patterns have a potential to serve as indicators for early events of an invasive/metastatic process. It remains to be seen whether the simultaneous occurrence of these patterns is a PTC-specific feature.     

Multiple brain metastases from a diffuse sclerosing variant of papillary carcinoma of the thyroid

We report a 53-yr-old man who presented with multiple brain metastases from a diffuse sclerosing papillary carcinoma of the thyroid. The presenting clinical features were those of an intracranial space-occupying lesion. Three brain tumors, confirmed pathologically to be metastatic thyroid papillary carcinomas, were removed. Two weeks after craniotomy, total thyroidectomy with cervical lymph node dissection was performed. Both lobes of the thyroid were diffusely enlarged and firm with a dominant mass. Histologically, the tumor was characterized by a combination of bilateral diffuse involvement of the gland, marked fibrosis, squamous metaplasia, abundant psammoma bodies, lymphocytic infiltration, frequent lymphatic and blood vessel permeation of the tumor, and typical elements of a conventional papillary carcinoma. In addition to these histologic findings, elements of other papillary carcinoma variants such as follicular and tall cell variants were also found focally. Twenty-three of twenty-four resected bilateral lymph nodes showed metastases of papillary carcinoma. Although the diffuse sclerosing variant of papillary carcinoma of the thyroid seems to be recognized as an aggressive variant of papillary carcinoma, there is no previous report of brain metastasis from this variant.     

NTRK3重排甲状腺乳头状癌的临床病理学特征

目的:探讨NTRK3重排甲状腺乳头状癌（PTC）的临床病理学特征、诊断和鉴别诊断。方法:收集2015年1月至2020年1月福建省立医院南院诊断的BRAF V600E阴性的PTC病例174例。对这些病例行免疫组织化学染色和荧光原位杂交（FISH）检测,筛选出NTRK3重排PTC的病例。总结确诊病例的临床资料、病理学特征、...     

Cytological features of clear cell thyroid tumors,including a papillary thyroid carcinoma with prominent hobnail features

Primary thyroid tumors with extensive clear cell changes are extremely rare. More than 10,000 ultrasound‐guided thyroid fine needle aspirations examined over a period of 17 years by the first author, only one of the 530 (<0.2%) papillary thyroid carcinomas (PTCs) and three of the 42 (7.1%) follicular thyroid carcinomas (FTCs) had extensive cytoplasmic clearing. Thyroidectomies were performed for these cases at four different hospitals in New York City. Final pathology was available for review in each of the four cases. Histology showed a 1.5‐cm PTC with prominent hobnail features and clear cell change in a 31‐year‐old woman, a 4.3‐cm FTC without angioinvasion in a 31‐year‐old woman, a 4.5‐cm angioinvasive FTC in a 45‐year‐old man, and a 2‐cm FTC with extensive angioinvasion in a 41‐year‐old woman with McCune–Albright syndrome (previously published). On ultrasound, the FTCs were solid circumscribed nodules and the PTC had an irregular margin. In these cases, the etiology for the cytoplasmic clearing included accumulation of glycogen in the PTC, accumulation of vesicles in two of the FTCs, and accumulation of lipid droplets in a FTC with extensive angioinvasion. Review of the cytologic literature showed 17 cases of follicular‐derived thyroid tumors with extensive clear cell change. To the best of our knowledge, this is the first cytologic report of PTC with hobnail features and extensive clear cell change. Diagn. Cytopathol. 2013;41:757–761. © 2012 Wiley Periodicals, Inc.     

Composite encapsulated papillary carcinoma and solid papillary carcinoma

Encapsulated papillary carcinoma (EPC) and solid papillary carcinoma (SPC) are distinctive variants of intraductal papillary carcinomas, each accounting for <1% of breast carcinomas. Here we report a composite carcinoma consisting of EPC and SPC. A 73‐year‐old woman was found to have a high density mass in the left breast on mammogram. A biopsy showed intermediate to high grade ductal carcinoma in situ (DCIS). Gross examination of the lumpectomy specimen revealed a solid, multinodular mass. Microscopic examination demonstrated two morphologically distinct intraductal carcinomas intermingled with each other. One had delicate papillae in multi‐cystic spaces surrounded by thick fibrous capsule, consistent with EPC. The other had solid tumor nests with delicate fibrovascular cores. The cells were monotonous with round nuclei and salt and pepper‐like chromatin, characteristic of SPC. The lack of myoepithelial cells within the papillae and at the periphery of the lesion was confirmed by immunostaining for p63 and CK5/6. Neuroendocrine differentiation of SPC was demonstrated by neuron specific enolase staining. To our knowledge, this is the first reported case of composite EPC and SPC. It raises an interesting question as to a possible common pathway of carcinogenesis of these two rare variants.     

Clear cell papillary renal cell carcinoma: a review

The disease concept of clear cell (tubulo) papillary renal cell carcinoma (CCP-RCC) as a distinct subtype of renal cell carcinoma has been recently established. First described in the setting of end stage renal disease, this tumor type is more frequently recognized and encountered in a sporadic setting. In this article, we provide an overview of the recent understanding of this tumor. Macroscopically, tumors are well circumscribed with well-developed tumor capsule. Histologically, the tumor cells are cuboidal to low columnar cell with clear cytoplasm and papillary and tubulo-papillary configuration. Immunohistochemically, tumor cells generally show diffuse expression for cytokeratin 7, CA9 (cup-shaped pattern), HIF-1, GLUT-1 and high molecular weight cytokeratin, but negative for AMACR, RCC Ma and TFE3. CD10 is negative or focally positive in most tumors. Genetically, this tumor has no characteristics of clear cell RCC or papillary RCC. Prognostically, patients with CCP-RCC behave in an indolent fashion in all previously reported cases. In conclusion, although this tumor has been integrated into recent International Society of Urologic Pathology Classification of renal neoplasia, both aspects of disease concept and clinical behavior are yet to be fully elucidated. Further publications of large cohorts of patients will truly help understand the biologic potential and the molecular underpinnings of this tumor type.