Hemangioendothelioma of the thyroid gland--true endothelioma or anaplastic carcinoma?

After a critical histological re-examination of 26 cases of malignant hemangioendothelioma of the thyroid, and a comparison with 51 cases of anaplastic spindle and giant cell carcinoma, it becomes obvious that traumatic and shrinkage artefacts due to fixation, as well as superimposition of neoplastic and repair processes due to regressive changes--almost always seen in malignant hemangioendothelioma associated nodular goiter--may be misinterpreted as neoplastic vascular spaces (and therefore angioblastic tumour differentiation). Focal epithelial arrangements of tumour cells often observed in these malignant hemangioendotheliomas and the lack of objective light microscopic differential diagnostic criteria of anaplastic spindle and giant cell carcinoma make the high incidence of endotheliomas of the thyroid in European endemic goiter regions very questionable. Compared with anaplastic spindle and giant cell carcinoma, the incidence for (1) extrathyroid tumours that infiltrate into the trachea or the oesophagus, (2) lymph node metastases and (3) distant metastases is not statistically different in malignant hemangioendothelioma. Therefore we conclude that the tumours classified as malignant hemangioendothelioma in goitrous areas represent a special growth pattern of anaplastic spindle and giant cell carcinoma within adenomatous glands rather than a distinct tumour type.     

Leiomyosarcoma: A Rare Tumor of the Thyroid

Primary leiomyosarcoma of the thyroid gland is uncommon. To date, 20 cases have been reported in English in the literature. The tumors usually present in elderly patients with female predilection and are associated with poor clinical outcome. Herein, we report an additional case of primary thyroid leiomyosarcoma in a 64-year-old woman. She underwent total thyroidectomy and later was discovered to have multiple lung and liver metastases. The patient died 3 months after surgery. The major differential diagnoses including undifferentiated (anaplastic) carcinoma of the thyroid, spindle cell variant of medullary thyroid carcinoma, spindle cell tumor with thymus-like differentiation, uncommon primary tumor of the thyroid and metastatic tumors with predominant spindle cells are discussed.     

Undifferentiated and poorly differentiated carcinoma

Undifferentiated (anaplastic) thyroid carcinoma is a highly aggressive neoplasm which may simulate microscopically a variety of soft tissue sarcomas. The three major subtypes are spindle cell, giant cell, and squamoid. Electron microscopic examination and immunocytochemical stain for cytokeratin are the most useful special techniques to document the epithelial nature of the tumor. Undifferentiated small-cell carcinoma is a term to be discarded. Nearly all tumors so designated in the past are malignant lymphomas, small-cell variants of medullary carcinomas, or poorly differentiated (insular) carcinomas. Poorly differentiated (insular) carcinoma is a thyroid malignant tumor characterized by the formation of solid nests and small follicles, a monotonous growth of small cells of follicular derivation, mitotic activity, necrosis, and peritheliomatous formation. Immunocytochemically, it is negative for calcitonin and positive for thyroglobulin. It is a clinically aggressive neoplasm, which metastasizes to both regional lymph nodes and distant organs. It is probably analogous to the tumor described by Langhans in 1907 as "wuchernde Struma."     

肿瘤相关抗原CA15—3在乳腺癌组织中的表达和意义

目的：探讨肿瘤相关抗原ＣＡ１５－３在良性与恶性乳腺病变及乳腺转移癌和非乳腺转移癌组织中的表达和意义。方法：应用免疫组织化学ＳＰ法检测８５例乳腺癌，２１例良性乳腺病变，１４例乳腺癌转移，１７例胃癌转移和３例鼻咽癌转移组织中的ＣＡ１５－３的表达情况，结果：８５例乳腺癌中ＣＡ１５－３阳性表达者为９２．９％其中癌细胞胞浆阳性占９２．４％，胞膜阳性占７．６％，２１例良性乳腺病变阳性表达为９０．５％，其中胞浆     

Tumor-to-tumor metastasis to follicular variant of papillary carcinoma of thyroid.

OBJECTIVE: To describe and document tumor-to-tumor metastases in the thyroid gland. METHODS AND RESULTS: In this series we describe 3 cases of tumor-to-tumor metastasis in which the recipient tumor was a follicular variant of papillary thyroid carcinoma. The donor tumors and sites were small cell carcinoma of the lung, neuroendocrine carcinoma probably of pancreatic origin with initial presentation as liver metastasis, and clear cell carcinoma of the kidney with metastasis to liver and pancreas. The donor tumor cells infiltrated the substance of the follicular variant of papillary thyroid carcinoma, the nontumorous thyroid parenchyma, and the lymphovascular spaces. Small cell carcinoma and neuroendocrine carcinoma showed positive reactivity for neuroendocrine markers and were negative for thyroglobulin and calcitonin. The follicular variant of papillary thyroid carcinoma showed positivity with thyroglobulin and cytokeratin 19. CONCLUSIONS: Although tumor-to-tumor metastases in thyroid gland are exceedingly rare, one should be aware of this phenomenon as the metastatic lesion may simulate a thyroid primary. History of a previous tumor and immunohistochemical stains can be helpful in distinguishing between primary and metastatic thyroid neoplasms.     

Myogenic expression in esophageal polypoid tumors

Four cases of esophageal polypoid tumors composed of squamous cell carcinoma and spindle cell sarcomatous components were investigated. Squamous cell carcinoma was consistently present in the base of the polypoid lesions in all four cases and was also intermingled with spindle-shaped sarcomatous cells in two cases. Metastases in the lymph nodes were observed in two cases: one was squamous cell carcinoma with a sarcomatous component and the other consisted of a pure sarcomatous component. All tumors involved at least the muscularis mucosae. In the sarcomatous region, the tumor was composed of highly anaplastic cells with or without forming interlacing fascicles. Pleomorphism was marked and bizarre giant cell forms were frequent. Mitoses were frequently present. Immunohistochemical study revealed that the anaplastic cells in the sarcomatous component in all cases were immunoreactive to desmin, muscle actin, vimentin, and alpha 1-antichymotrypsin, but were negative for cytokeratin, even in the metastatic tumors of the lymph nodes. The immunohistochemical results favor myogenic differentiation of the anaplastic cells, and these tumors were considered to be true carcinosarcomas composed of squamous cell carcinoma and leiomyosarcoma.     

Detailed Lymph Node Sectioning of Papillary Thyroid Carcinoma Specimen Increases the Number of pN1a Patients

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy, frequently presenting with lymph node metastasis at the time of diagnosis. Lymph node staging (N) partly determines treatment, follow-up, and prognosis. Since 2011, our institution has employed a more comprehensive histopathological work-up of lymph nodes in patients with PTC. We sought to retrospectively determine the value of serial lymph node level sectioning in PTCs with negative preoperative lymph node status (pN0) as a method to increase the sensitivity of detecting metastatic disease. We included all patients that underwent thyroidectomy and central neck dissection and subsequent comprehensive lymph node level sectioning due to PTC with an initial pN0 status between the years 2011 and 2015 at our institution. Sixty-seven cases of PTC with a median of 10 metastatic free lymph nodes identified per case were included. After serial lymph node sectioning of the central compartment, 11 cases (16 %) revealed lymph node metastasis, six of which (55 %) presented with a small primary tumor (<20 mm, T1). Of all T1 tumors with initial pN0 status, 18 % (T1a) and 9 % (T1b) reached a pN1 stage after comprehensive lymph node sectioning. Cases with altered lymph node status had a median of 15 identified lymph nodes as compared to ten in cases that remained negative. We conclude that comprehensive lymph node sectioning increased the sensitivity of detecting metastases in PTC and altered the pathological TNM staging (pTNM) for a significant number of patients. Although of limited prognostic significance, the method should be considered as an adjunct tool when assessing lymph node status of PTC as a part of the routine histological work-up to ensure an accurate cancer staging.     

Duodenal gangliocytic paraganglioma with regional lymph node metastasis and a glandular component

Gangliocytic paraganglioma (GP) is generally considered to be a benign periampullary lesion, although it is unclear whether it should be classified as a hamartoma or as a neoplasm. Here, we present a GP case with lymph node metastasis. A 16-year-old boy complained of exertional dyspnea. Upper endoscopy and imaging studies revealed a polypoid ampullary tumor. Pancreaticoduodenectomy with lymph node dissection was performed due to swelling of peripancreatic lymph nodes. Histologically, the tumor consisted of three cell types: epithelioid; spindle; and ganglion cells. In addition to these typical components of GP, a distinct glandular component was also present. There was substantial invasion of tumor cells into the lymphovascular vessels, associated with lymph node metastases. These lymph node metastases were histologically similar to the primary tumor. To judge from these findings GP may be a true neoplasm with metastatic capacity. Pre- and intraoperative investigations for lymph node or distant metastases are required for adequate resection of this kind of tumor.     

LIMD2 Is Overexpressed in BRAF V600E-Positive Papillary Thyroid Carcinomas and Matched Lymph Node Metastases

We previously described that LIM domain containing 2 (LIMD2) overexpression was closely correlated with metastatic process in papillary thyroid carcinoma (PTC). We here evaluated the expression of LIMD2 in a series of non-metastatic and metastatic PTC and their matched lymph node metastases via immunohistochemistry. LIMD2 was expressed in 74 (81%) of primary PTC and 35 (95%) of lymph node metastases. Sub-analysis performed in 37 matched samples demonstrated that in four cases, LIMD2 is expressed in lymph node metastases, while it is not expressed in primary tumors. Moreover, in eight cases, the staining intensity of LIMD2 was stronger in the patient-matched lymph node metastases than in the primary tumors. Next, the expression of LIMD2 was correlated with clinical pathological parameters and BRAF V600E and RET/PTC mutational status. The expression of LIMD2 in primary tumors was correlated with the presence of BRAF V600E mutation (P =?0.0338). Western blot analysis in thyroid cell lines demonstrated that LIMD2 is expressed in two PTC cell lines, while it is not expressed in normal thyroid and follicular thyroid carcinoma cell lines. Importantly, its expression was higher in a PTC cell line that harbors BRAF V600E mutation than in a PTC cell line that harbors RET/PTC1. The available genomic profiling data generated by The Cancer Genome Atlas Research Network confirmed that LIMD2 expression is higher in BRAF-like PTC samples. Our data suggest that LIMD2 may play an important role in the metastatic process of PTC, predominantly in BRAF V600E-positive tumors.     

Bone metastases from thyroid carcinoma: a histopathologic study with clinical correlates

CONTEXT: Only limited information exists on the pathologic aspects of thyroid carcinomas with bone metastases, most large studies having concentrated mainly on their clinical features. OBJECTIVE: To study in detail the morphologic features of thyroid carcinomas with skeletal metastases. DESIGN: Seventy-nine cases of thyroid carcinoma with bone metastases treated at Memorial Sloan-Kettering Cancer Center, New York, NY, between 1964 and 1998 were investigated, with emphasis on the pathology of the primary and/or metastatic tumors and comparison of the morphologic features of the tumors at both the sites, wherever possible. The tumors were also compared for various clinical parameters. RESULTS: The cohort consisted of 22 papillary, 17 follicular, 16 insular, 10 anaplastic, 9 Hürthle cell, and 5 medullary carcinomas. Of these cases, 68% had poorly differentiated or undifferentiated features in the primary and/or metastatic tumors. The metastatic tumors were better differentiated than the primary in one third of the cases (6 of 18). Only one case showed a less differentiated metastasis. The overall 5- and 10-year survival probabilities after the bone metastases were 29% and 13%, respectively (Kaplan-Meier method). Although both the tumor type and differentiation seemed to affect survivals after bone metastasis (P =.007 and.012, respectively) (log-rank test), this was primarily due to the much worse prognosis in the cases of anaplastic and medullary carcinoma. Cases of Hürthle cell carcinoma showed the longest median survival. There was no significant difference in survival among patients up to or older than 45 years at the time of metastases (P =.31). CONCLUSIONS: Most thyroid carcinomas with bone metastases are of papillary type, and most have poorly differentiated or undifferentiated features. The influence of the microscopic tumor type and tumor differentiation on survival after bone metastasis primarily appears to be due to the much worse prognosis among anaplastic and medullary carcinomas. Age at diagnosis of bone metastases does not influence survivals.     

Bronchogenic sarcomatoid squamous cell carcinoma with osteoclast-like giant cells

A 60-year-old man developed a widely metastatic spindle cell neoplasm with admixed osteoclast-like giant cells indistinguishable from malignant giant cell tumor of soft parts. Autopsy revealed a bronchogenic sarcomatoid squamous cell carcinoma that was the primary source of the sarcomatoid metastases. The osteoclast-like giant cells in the metastatic lesions were negative for lysozyme on immunoperoxidase staining. This finding suggested that the multinucleated giant cells were not formed as a cellular response to hemorrhage or to cellular debris induced by the tumor. Extraosseous neoplasms with osteoclast-like giant cells are rare neoplasms that may occur in a variety of organs. This case is the second reported case of a primary neoplasm in the lung that contained these osteoclast-like giant cells. These tumors may cause considerable diagnostic confusion.     

Mucinous tubular and spindle cell carcinoma of kidney without sarcomatoid change showing metastases to liver and retroperitoneal lymph node

Mucinous tubular and spindle cell carcinoma (MTSCC) is an uncommon, newly recognized tumor that in its classic histological form shows tightly packed, elongated tubules with transition into spindle cell areas and pale mucinous stroma. The current data suggest that the great majority of MTSCCs have a favorable prognosis; however, the follow-up data are limited and the full biologic potential of this tumor remains to be established. There are a few examples of MTSCCs metastatic to lymph nodes and rare cases with sarcomatoid differentiation associated with distant metastases. We report on a case of MTSCC of kidney with concurrent nodal and liver metastases. The metastatic nodules were well circumscribed and showed morphological and immunophenotypic features similar to those of the primary tumor. Extensive sampling revealed no evidence of sarcomatoid morphology. To our knowledge, this is the first case of MTSCC without sarcomatoid differentiation showing parenchymal metastasis.     

Papillary Thyroid Carcinoma with Predominant Spindle Cell Component: Report of Two Rare Cases and Discussion on the Differential Diagnosis with Other Spindled Thyroid Neoplasm

Spindle cell transformation or metaplasia has been so far demonstrated in the context of both benign and malignant conditions. Spindle cell lesions of the thyroid gland of either primary or secondary origin to metastatic disease represent rare entities. We describe two patients with papillary thyroid carcinoma (PTC) showing spindle cell metaplasia, submitted to thyroidectomy due to euthyroid bilateral nodular thyroid disease. Cytological examination of fine-needle aspiration biopsy performed in the dominant nodules was consistent with follicular neoplasm in one case and with a hyperplastic/adenomatous nodule in the other patient. Histological examination disclosed unencapsulated follicular variant of PTC with spindle cell metaplasia in either cases. Both patients are doing well without clinical or laboratory evidence of PTC recurrence at 3- and 1-year follow-up, respectively. We present the clinical, pathological, and immunohistochemical aspects of these unusual cases and thoroughly discuss the differential diagnosis with other spindle cell lesions of the thyroid gland.     

Mucinous breast carcinoma metastatic to thyroid gland: Report of a case diagnosed by fine‐needle aspiration cytology

Mucinous breast cancer is a slow‐growing neoplasm, which has fewer lymph node metastases and favorable prognosis compared with invasive breast cancer no special type. The hematogenous spread of breast mucinous carcinoma is very rare. Though breast cancer involving thyroid has been reported before, there is still no report about thyroid metastatic breast mucinous carcinoma in the literature. Recently by performing thyroid fine‐needle aspiration, a 58‐year‐old woman who had breast cancer 13 years ago was diagnosed as thyroid metastatic mucinous breast carcinoma, cellular variant with neuroendocrine differentiation. For this patient, the thyroid was the only involved site without widespread metastatic diseases, so thyroidectomy and the right cervical lymph nodes dissection were performed to make better survival. As a result, the patient had not shown any signs of recurrence 9 months after the thyroid surgery.     

Unusual Thyroid Carcinoma Metastases: a Case Series and Literature Review

The most common sites of metastatic differentiated thyroid cancer are the neck lymph nodes, while distant metastases typically involve the lungs, the bones, and less frequently the brain. Uncommon metastatic sites include the liver, adrenal gland, kidney, pancreas, and skin. The epidemiological aspects of thyroid metastases in rare sites are largely unknown and their identification could have a significant impact on patients management. A mini-series of unusual metastatic sites of thyroid carcinoma is proposed as a contribution to current knowledge on anatomopathological characteristics and clinical outcome. Of the six cases that were assessed, the metastases were the following: skin metastases (2), skin and pancreas metastases (1), renal metastasis (1), adrenal metastasis (1), and liver metastasis (1). In our experience, metastases in rare sites do not always represent a negative prognostic factor for disease outcome. In fact they can occur as single distant lesion and if surgically resectable, their treatment can also lead to local disease remission.     

The Quarterly Case: Metastatic Tumor of Unknown Origin

Material from 41 patients with primary breast carcinoma and lymph node metastases at the time of primary surgical intervention was immunostained for c-erbB-2 protein, neuron-specific enolase (NSE), and estrogen receptors. Thirty of the primary breast carcinomas were of ductal type. Six were classified as infiltrating lobular carcinomas, 2 were apocrine, 1 was mucinous, and 1 was a tubular carcinoma. One tumor could not be classified as ductal or lobular by light microscopic examination alone. The number of lymph node metastases available varied from 1 to 14 per case (median, 3.9). Nine (22%) of the primary breast carcinomas (8 ductal and 1 apocrine) expressed c-erbB-2 protein and showed c-erbB-2 gene amplification; 12 expressed NSE immunoreactivity. None expressed both markers. Estrogen receptor immunoreactivity was present in 23 of the 41 cases, including 9 of the NSE-positive cases. C-erbB-2 protein-positive metastases were present in 18 cases (44%), and in 13 cases all metastases were immunostained. In 5 cases the expression of c-erbB-2 protein varied from metastasis to metastasis. NSE immunoreactivity was expressed in 10 cases, and in 3 cases with minor NSE-positive cell populations the metastatic lesions expressed c-erbB-2 protein as well. All 9 primary breast carcinomas expressing c-erbB-2 protein had lymph node metastases with c-erbB-2-immunoreactive tumor cells. Eight of the 9 c-erbB-2 protein-negative primary tumors with metastases expressing c-erbB-2 protein showed no amplification of the c-erbB-2 gene. Thus expression of c-erbB-2 protein can occur during the metastatic process, even if it seems to be missing in the primary tumor. On the other hand, if a primary breast carcinoma expresses c-erbB-2 protein, this feature seems to be present in all the tumor metastases as well.     

The c-erbB-2 Protein in Primary and Metastatic Breast Carcinomas

Material from 41 patients with primary breast carcinoma and lymph node metastases at the time of primary surgical intervention was immunostained for c-erbB-2 protein, neuron-specific enolase (NSE), and estrogen receptors. Thirty of the primary breast carcinomas were of ductal type. Six were classified as infiltrating lobular carcinomas, 2 were apocrine, 1 was mucinous, and 1 was a tubular carcinoma. One tumor could not be classified as ductal or lobular by light microscopic examination alone. The number of lymph node metastases available varied from 1 to 14 per case (median, 3.9). Nine (22%) of the primary breast carcinomas (8 ductal and 1 apocrine) expressed c-erbB-2 protein and showed c-erbB-2 gene amplification; 12 expressed NSE immunoreactivity. None expressed both markers. Estrogen receptor immunoreactivity was present in 23 of the 41 cases, including 9 of the NSE-positive cases. C-erbB-2 protein-positive metastases were present in 18 cases (44%), and in 13 cases all metastases were immunostained. In 5 cases the expression of c-erbB-2 protein varied from metastasis to metastasis. NSE immunoreactivity was expressed in 10 cases, and in 3 cases with minor NSE-positive cell populations the metastatic lesions expressed c-erbB-2 protein as well. All 9 primary breast carcinomas expressing c-erbB-2 protein had lymph node metastases with c-erbB-2-immunoreactive tumor cells. Eight of the 9 c-erbB-2 protein-negative primary tumors with metastases expressing c-erbB-2 protein showed no amplification of the c-erbB-2 gene. Thus expression of c-erbB-2 protein can occur during the metastatic process, even if it seems to be missing in the primary tumor. On the other hand, if a primary breast carcinoma expresses c-erbB-2 protein, this feature seems to be present in all the tumor metastases as well.     

Solid-pseudopapillary neoplasm of pancreas with long delayed liver metastasis

Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that most commonly affects adolescent girls and young women. Solid-pseudopapillary neoplasm of the pancreas is considered to have malignant potential; 10% to 15% of cases are associated with metastasis, and these usually present at the time of initial diagnoses. Cases with metastases after resection are rare, and all reported cases have occurred less than 5 years after resection. We report a case of SPN in a 36-year-old woman who presented with liver metastasis 15.8 years after complete resection of the primary tumor in the pancreas. To the best of our knowledge, this is the longest time interval reported between resection of primary tumor and subsequent detection of metastatic disease. Solid-pseudopapillary neoplasm of the pancreas can present with metastases many years after resection of the primary tumor. Long-term follow-up is warranted, given the possibility of late metastasis.