Tumor-to-tumor metastasis to a thyroid follicular adenoma as the initial presentation of a colonic adenocarcinoma

The incidence of thyroid involvement by metastatic disease from distant organs ranges from an average of 3.1% in surgical series to 5.3% in autopsy series. However, the metastasis of one tumor into another (traditionally referred to as 'tumor-to-tumor metastasis') is distinctly uncommon. Typically, they are identified as new manifestations or necropsy findings of a known, pre-existing donor tumor. Herein is described the case of a 59-year-old woman whose thyroid nodule (a follicular adenoma) was resected and found to contain foci of a well-differentiated adenocarcinoma with a morphologic and immunohistochemical profile consistent with origination from the lower gastrointestinal tract. Subsequent diagnostic work-up revealed a sigmoid colon tumor with metastases to the liver. This is, to the authors' knowledge, the first reported example of a colon adenocarcinoma whose initial clinical manifestation was a metastasis to a thyroid neoplasm and only the third reported example of a colonic adenocarcinoma metastatic to a thyroid tumor. In a review of previously reported examples of tumor-to-tumor metastases involving a thyroid neoplasm as the recipient, the following features were present in the majority: (i) multifocality of the metastatic tumor aggregates; (ii) a total lack of, or only minimal amounts of reaction (desmoplastic, inflammatory or myxoid) of the recipient tumor to the metastatic deposits; and (iii) retention of the histopathologic characteristics of the donor tumor in the metastatic deposits. In general, strikingly divergent morphologic features in an otherwise typical thyroid neoplasm should elicit a differential diagnosis that takes into consideration the possibility of metastasis.     

Image cytometry of insular carcinoma

To study the morphometric features of insular carcinoma (IC) of thyroid and follicular carcinoma (FC) in fine needle aspiration cytology (FNAC) smear to evaluate the role of the morphometric features to distinguish these two groups. We performed image morphometry in Hematoxyline and Eosin stained FNAC smears of eight each histopathology proven cases of IC and FC of thyroid. Nuclear area, diameter, perimeter, and standard deviation of nuclear area (SDNA) of these two groups were studied and compared. Nuclear area, diameter, perimeter, and SDNA of IC and FC were 30.43 μ(2) , 7.31 μ, 23.01 μ, 8.81 and 38.43 μ(2) , 7.66 μ, 25.63 μ, 10.83, respectively. Student's t-test analysis did not show any significant difference (P > 0.05) in these two groups. Nuclear morphometry data indicate that the nuclear size and shape of IC and FC are essentially similar and it is not possible to differentiate these two entities with the help of image morphometric data.     

The encapsulated follicular carcinoma of the thyroid

Summary In a retrospective study of 86 follicular carcinomas of the thyroid gland, 35 lesions were classified as encapsulated carcinomas (40.7%). In two of these, lymph node metastases were detected initially. Another patient presented with distant metastases. The biological behaviour of these 35 tumours was studied over a long-term follow-up period (0.4–19.1 years, mean 10.3 years) which featured three cases of death from thyroid carcinoma 0.4–5.0 years after thyroidectomy. Another patient suffered from local recurrence of a follicular carcinoma 13.9 years later. The morphological and clinical findings of those five patients who initially presented with metastases and/or whose follow-up registered the local recurrence of thyroid cancer or death as a result of it, were compared with the remaining 30 cases which were of a benign clinical course. Statistical analysis showed that the prognosis of encapsulated follicular carcinoma is more serious when tumours occur in patients older than 65 years of age and when the tumour diameter is 5.0 cm or more. There was a tendency towards poorer prognosis in those tumours exclusively composed of oxyphilic epithelium.Sponsored by: Hamburger Stiftung zur Förderung der Krebsbekämpfung     

Late bone metastasis from an encapsulated follicular carcinoma of the thyroid withoutcapsular and vascular invasion

A unique case of encapsulated follicular carcinoma of the thyroid, which lacked histologic evidence of capsular and vascular Invasion but developed a late bone metastasis, is described. The thyroid tumor was found in a 42-year-old man. It was relatively small (2.5 cm) and totally encapsulated. Histologically, the thyroid tumor showed a microfollicular growth pattern of follicular cells and revealed no histologic evidence of nuclear atypia, mitotic figures or capsular and vascular invasion. The diagnosis of microfollicular adenoma was made and partial thyroidectomy was performed. Bone (rib) metastasis of the thyroid tumor developed 22 years after the thyroidectomy. The present case suggested that capsular and/or vascular invasion is not always sufficient for the diagnosis of encapsulated follicular carcinoma of the thyroid.     

Dipeptidyl peptidase IV (DPP IV/CD26) staining predicts distant metastasis of 'benign' thyroid tumor

Because follicular thyroid carcinoma is extremely difficult to diagnose, several cases were encountered which have been rediagnosed as carcinoma due to distant metastasis. In the search for a method of correctly diagnosing 'benign' thyroid tumor, dipeptidyl peptidase (DPP) IV immunostaining was applied to 10 cases whose diagnoses had been corrected to follicular thyroid carcinoma because of distant metastases. The positive rate of immunostaining using paraffin sections in the rediagnosed follicular thyroid carcinoma group (7/10) was much higher than that of the control group (1/29), which consisted of 15 cases of follicular thyroid adenoma and 14 cases of nodular hyperplasia. These results suggested that pre- or postoperative DPP IV staining is useful for predicting distant metastasis of 'benign' thyroid tumor.     

Incidentally detected liver metastasis of well-differentiated follicular carcinoma of the thyroid, mimicking ectopic thyroid

A case of incidentally detected liver metastasis of follicular carcinoma of the thyroid, histologically mimicking ectopic thyroid, is described. The patient was a 48-year-old woman. A 2-cm mass was incidentally detected in the left lobe of the liver by abdominal computed tomography (CT) scan. Partial liver resection was performed for diagnosis and treatment. Histologically, the liver nodule was composed of small-to-large follicles containing colloid material. The lining epithelium was flat or cuboidal and showed no cellular or nuclear atypia. Immunohistochemical studies for thyroid-specific proteins, thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4), suggested that the nodule was of thyroid origin. Therefore, a differential diagnosis of metastasis of well-differentiated thyroid cancer, ectopic thyroid tissue and teratoma was made. The patient had a history of subtotal thyroidectomy performed 8 years ago due to a thyroid tumor. The original surgical specimens of the thyroid tumor were diagnosed as follicular adenoma. Additional sections of the specimen were reviewed and an area of convincing vascular invasion was found that was suggestive of follicular carcinoma. Subsequent whole-body examination failed to find other metastases. It was determined that the liver tumor was metastasized from well-differentiated follicular carcinoma of the thyroid.     

Skull metastasis from follicular thyroid carcinoma: report of three cases and review of literature

Three patients’ medical history, clinical manifestation, imaging characteristic, therapy and prognosis of calvaria metastasis from follicular thyroid carcinoma (FTC) in our hospital were retrospectively analyzed by reviewing medical literature. In case one, the tumor in frontal bone and fossa orbital was total resected, no further treatment was performed, the patient gave up on therapy and died of extensive metastasis at 22 months after the initial operation. In case two, the tumor in parietal and occipital bone was total resected, the subtotal resection of bilateral thyroid gland and isthmus was performed and combined with therapy of Levothyroxine and ¹³¹I radio-iodine therapy, no evidence of tumor recurrence at 30 months after the primary operation. In case three, the tumor in occipital bone was gross total resected, total resection of bilateral thyroid gland and clearance of lymph node was performed after two months, adjunctive therapy with Levothyroxine, ¹³¹I radio-iodine and skull radiotherapy, no evidence of tumor recurrence at 21 months after the primary operation. Correct diagnosis of calvaria metastasis from FTC preoperative is difficult because it’s rarity, patients can survive for years after synthetic therapy including total resection of metastatic tumor, radical operation of thyroid carcinoma, adjunctive therapy of Levothyroxine, ¹³¹I radio-iodine and skull radiotherapy.     

Fine-needle aspiration of an unusual case of poorly differentiated insular carcinoma of the thyroid

Poorly differentiated insular carcinoma of the thyroid is a rare thyroid malignancy that is intermediary in biological behavior between well-differentiated and undifferentiated thyroid carcinoma. We used fine-needle aspiration (FNA) to diagnose a poorly differentiated insular carcinoma with unusual cytological features in a 53-yr-old woman with a history of goiter and hypothyroidism, who presented with a massively enlarged thyroid gland and a large liver metastasis. The hypercellular aspirates were comprised predominantly of individually dispersed tumor cells. The tumor cells were small, monotonous, round to oval, and often plasmacytoid with eccentric hyperchromatic nuclei and occasional binucleation; finely granular, ill-defined cytoplasm; and smooth nuclear contours, with hyperchromasia, and small to inconspicuous nucleoli. There were no identifiable microfollicles, necrosis, and mitotic figures. The differential diagnosis included poorly differentiated insular carcinoma, medullary carcinoma of the thyroid, and low-grade lymphoma. Immunocytochemical staining for thyroglobulin, calcitonin, and CD45 yielded negative findings. The insular pattern and scattered microfollicles were appreciated only focally in the specimen from the total thyroidectomy, which also showed other histological patterns including solid, trabecular, and papillary forms. In addition to small, uniform cells, Hurthloid, columnar, and clear cells were focally noted. Thyroglobulin immunoreactivity was recognized only in areas with well-formed follicles. In view of the aggressive nature of insular carcinoma, preoperative recognition is important in planning appropriate therapy. Familiarity with the cytomorphological features, a high index of suspicion, and consideration of appropriate differential diagnoses can greatly aid in reaching a definitive preoperative diagnosis. The limitations of FNA in the sampling of a large tumor with heterogeneous patterns should be kept in mind when interpreting the cytomorphological and immunocytochemical results.     

Where to set the threshold between well differentiated and poorly differentiated follicular carcinomas of the thyroid

A critical review of the literature reveals that different types of thyroid carcinomas have been interpreted as poorly differentiated, including the tall and columnar cell variants as well as carcinomas with insular, trabecular, and solid growth patterns. In some publications the growth patterns have been emphasized, while in others histologic patterns and cytologic features are considered important for identification. However, insular, trabecular, nodular, and solid growth patterns lack specificity because they can be observed in hyperplastic lesions and benign thyroid tumors. The cytologic features of the vast majority of poorly differentiated thyroid carcinomas are similar to or overlap with those of papillary or follicular carcinomas. Cytologic atypia, mitotic activity, and necrosis—believed by some investigators to be useful clues in the diagnosis of poorly differentiated carcinomas—do not reflect cell differentiation, especially in endocrine organs. It is therefore not surprising that the immunohistochemical profile and the molecular abnormalities described in this heterogeneous group of carcinomas lack specificity and are not useful diagnostic tools. Because poorly differentiated thyroid carcinomas have not been well defined, currently it is not possible to set the threshold between well-differentiated and poorly differentiated thyroid carcinomas with follicular phenotype. The authors believe that the vast majority of poorly differentiated thyroid carcinomas are in fact examples of papillary or follicular carcinomas with unusual growth patterns.     

Cytopathology of insular carcinoma of the thyroid.

Four pure insular carcinomas (IC) and one IC with focal anaplastic carcinoma (AC) of the thyroid with cytologic evaluation by fine-needle aspiration (FNA) were reviewed. The needle aspirates from the four pure ICs revealed abundant monomorphic follicular cells present singly, in small, loose aggregates, and in cohesive trabecular and acinar clusters. Tumor cells showed fragile, ill-defined, granular cytoplasm and oval nuclei with conspicuous or inconspicuous nucleoli. The case of IC with focal AC yielded, in addition to the follicular cells as seen in the FNA of the 4 cases of pure IC, large pleomorphic malignant cells with prominent nucleoli that were characteristic for an AC, giant-cell type. No intact insulae of tumor cells were identified in any of the 5 cases. Thus, a thyroid IC may be suspected if abundant cohesive and dyshesive monomorphic follicular cells are present in the tumor FNA. However, a firm diagnosis of thyroid IC can only be made by histologic examination of the excised tumor.     

Fine needle aspiration cytology of insular carcinoma of thyroid

Poorly differentiated (insular) thyroid carcinoma is defined as a thyroglobulin-producing non-follicular non-papillary thyroid carcinoma, having an intermediate behavior between well-differentiated and anaplastic carcinomas. FNAC is widely used as aid for workup of thyroid gland lesion. However, scant information is available in the literature about cytologic findings of this rare entity. Ten cases of surgically resected insular carcinoma with a corresponding cytology were selected. The cytologic smears and histological sections were reviewed for presence of cytomorphologic features including cellularity, predominant cytoarchitectural pattern, additional cytologic co-patters pattern, cell size, cell shape, nuclear pleomorphism, nuclear/cytoplasmic (N/C) ratio, chromatin pattern, amount of cytoplasm, mitotic figures, colloid, background debris, nuclear grooves, and intranuclear pseudoinclusions. In all the cases, the cells were arranged predominantly in solid clusters. Focal microfollicular pattern was identified in five cases of which three cases showed presence of inspissated colloid within the follicles. Singly scattered malignant cells and bare nuclei were seen in all cases. Cells were monomorphic, round with high N/C ratio, finely granular chromatin and inconspicuous nucleoli. Background showed presence of cellular debris in two cases. Mitotic figures were obvious and atypical mitosis was also identified. Cellular smears composed of monomorphic population of small cells arranged in large clusters and sheets with high N/C ratio and high mitosis suggest the possibility of insular carcinoma. Background cellular debris/necrosis also supports the diagnosis. Cell block preparation in these cases may be of additional help in accurate diagnosis.     

Tumor-to-tumor metastasis: lung adenocarcinoma metastasizing to a follicular variant of papillary thyroid carcinoma

Cancer-to-cancer metastasis into a thyroid neoplasm is an uncommon phenomenon with possible diagnostic difficulties. Here, we describe a case of lung adenocarcinoma metastatic into a follicular variant of papillary thyroid carcinoma (FVPTC). A 60-year-old woman with no prior history of malignant neoplasm presented with a nodule in the right lobe of the thyroid gland, some masses in the left lung were found by radiological examination. Histopathological examination of the thyroidectomy specimen demonstrated two different components of carcinoma in a single thyroid nodule; one was FVPTC and the other was high-grade adenocarcinoma. Although both components shared the TTF-1+/CK7+/CK19+/CK20-/SP-A- immunoprofile, only the former was positive for thyroglobulin, and only the latter was positive for CEA. The epidermal growth factor receptor (EGFR) gene mutation at exon21 (L858R) was present only in the latter. The lung biopsy specimen showed cytological, immunohistochemical, and EGFR genotypic features similar to those of the high-grade adenocarcinoma component of the thyroid nodule. These findings resulted in a reliable diagnosis of lung adenocarcinoma metastasizing into an FVPCT and treatment with EGFR-targeted therapy. These results demonstrate that a panel of immunohistochemical staining and molecular analysis is helpful for both diagnosis and appropriate postoperative treatment for a patient with cancer-to-cancer metastasis.     

结直肠癌同时及异时性远处转移的临床病理特征

目的:回顾性分析结直肠癌同时性与异时性远处转移患者的临床病理特征及预后影响因素.方法:收集2010年1月至2015年12月间128例结直肠癌远处转移患者完整的临床病理资料,根据转移发生的时间分为两组:同时转移组(79例)、异时转移组(49例).比较两组临床病理特征,分析影响远处转移患者预后的因素.结果:同时性远处转移患者与肿瘤原发部位(P=0.025)、浸润深度(P=0.002)、分化程度(P=0.008)及脉管癌栓(P=0.012)有关;同时性远处转移患者中位生存期为19(12~28)个月,异时性远处转移患者中位生存期为20(13~28)个月,两组之间差异无统计学意义(P=0.866);多因素生存分析结果提示,肿瘤浸润深度(P<0.001)、肿瘤分化程度(P=0.002)、脉管癌栓(P=0.006)及转移器官数量(P=0.001)是影响远处转移预后的独立因素.结论:根据结直肠癌不同时期发生远处转移患者表现出的临床病理特点,可以有效估计可能发生远处转移的患者及预后情况.     

Insular component as a risk factor of thyroid carcinoma

Forty-four thyroid carcinomas with an Insular component (JC) were reviewed from 2457 tumors diagnosed as papillary (PC) or follicular carcinoma (FC). These tumors were classified as FC with an IC (FCIC; 30 cases) and PC with an IC (PCIC; 14 cases). Both tumors were composed of solid cell nests in some areas and had a tendency toward a characteristic nuclear size: FCIC had a small nucleus and PCIC contained a nucleus of an Intermediate type or a large nucleus similar to that of PC, although there were numerous tumors with an exceptional nuclear size. The mean age and tumor diameter were the highest and largest in FCIC, respectively, followed by PCIC. Among the 44 cases, 17 patients died of the disease, two were alive with the disease and 18 were alive without the disease. From 13 clinicopathological factors, the presence of an IC, age, non-encapsulation, tumor size, vascular invasion and necrosis were found to be independent variables for actual prognosis of FC and PC based on univariate analysis followed by multtvariate analysis. The results of the present study indicate that the presence of an IC is an independent aggressive prognostic factor for patients with PC and FC.     

Salivary duct carcinoma metastatic to inguinal lymph node: a case report of salivary duct carcinoma with distant metastasis diagnosed by fine-needle aspiration

Salivary duct carcinoma (SDC) is a high-grade malignant tumor exhibiting aggressive growth with early regional and distant metastasis. We report a case of SDC in a 53-yr-old male with distant metastasis to an inguinal lymph node. The diagnosis of the primary tumor as well as the metastatic lesion was accomplished by fine-needle aspiration (FNA). Aggressive clinical management appears to be the main therapeutic option for long-term survival. Therefore, establishing an accurate preoperative diagnosis by FNA can have both clinical and prognostic relevance.     

Medullary thyroid carcinoma,follicular variant

We report here a 48-yr-old woman presenting with a solitary thyroid nodule in the left lobe of the thyroid. The aspiration cytology of the nodule was reported as follicular neoplasia and she underwent surgery. Frozen section was suspicious for medullary thyroid carcinoma and a total thyroidectomy was performed. The pathology report revealed medullary thyroid carcinoma, follicular variant. Immunohistochemical analysis was negative for thyroglobulin and positive for calcitonin. A few patients with this variant have been reported in the literature, mainly diagnosed by immunohistochemical features of the tumor. In light of the limited information we have obtained from the literature, it is reasonable to emphasize that these cases should be distinguished from the mixed medullary-follicular thyroid carcinomas and medullary carcinomas with entrapped follicles. Immunohistochemical examination with calcitonin and thyroglobulin is also essential.