Combined "Mixed Medullary-Follicular" and "Papillary" Carcinoma of the Thyroid with Lymph Node Metastasis

We report a case of combined “mixed medullary-follicular” and “papillary” carcinoma of the thyroid that occurred in a 44-yr-old Japanese woman. The grossly single 3 cm tumor was histologically composed of both mixed medullary-follicular carcinoma and papillary carcinoma, which abutted against each other with a clear border between two components. Immunohistochemically, the component of medullary carcinoma was positive for calcitonin and carcinomebryonic antigen (CEA), and the follicular carcinoma and papillary carcinoma components were positive for thyroglobulin. Lymph node metastasis was also noted. The patient has been alive without recurrence for 20 yr. To the best of our knowledge, this is the first reported case in the literature. We report this unique case of thyroid carcinoma and review related thyroid malignancies.     

Well-Differentiated Thyroid Carcinoma with Concomitant Hashimoto’s Thyroiditis Present with Less Aggressive Clinical Stage and Low Recurrence

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the most common differentiated thyroid cancers. Previous studies report that Hashimoto’s thyroiditis (HT) concomitant with PTC is unusual and improves prognosis compared to classical PTC. Few previous studies address FTC concomitant with HT. In this study, we retrospectively analyzed data from one institution and compared clinical presentations and results of treatment of PTC and FTC with and without HT. In addition, studies comparing presentation and long term follow-up prognosis in classical PTC and FTC were conducted. A total of 1,788 PTC patients and 209 FTC patients underwent thyroidectomy with or without lymph node dissection and follow-up at Chang Gung Medical Center in Linkou, Taiwan. All thyroid carcinomas were pathologically classified according to World Health Organization criteria. Histological patterns of PTC were categorized as classical PTC, or PTC with HT. Follicular thyroid carcinoma patients were categorized as FTC or FTC with HT. The dataset contained a total of 1,703 PTC cases categorized as classical PTC, 85 cases of PTC with HT, 201 cases of FTC and eight cases of FTC with HT. Analysis of Classification of Malignant Tumors (TNM) stage revealed a higher percentage of classical PTC in stage IV than HT group (12.03% vs. 4.70%). Mean tumor size of classical PTC was larger than HT group. Although 42.3% of FTC cases presented with distant metastases, no cases of FTC with HT presented with distant metastasis. Cancer-specific mortality was higher in classical PTC group than in PTC with HT. There was 53.2% of FTC without HT assigned recurrent status, and six of them died of thyroid cancer. No cancer mortality or recurrence in HT with FTC. PTC and FTC with HT presented with better clinical stage and better prognosis after same therapeutic modality. In conclusions, both PTC and FTC with HT have less aggressive clinical presentation and better prognosis.     

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.     

Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological study of 12 cases

AIMS: To analyse the clinical and pathological features with long-term follow-up of a series of 12 cases of sarcomatoid carcinoma of the breast. methods and results: The cases were selected from the surgical files of the Department of Pathology, University of Edinburgh, between 1977 and 1988. The following clinical parameters were recorded: the age of the patients, size of tumour, presence or absence of lymph node or distant metastases, and patient survival. Pathological assessment included: the type of epithelial and mesenchymal components, the proportion of monophasic to biphasic tumours and the presence of adjacent in-situ carcinoma/atypical epithelial proliferation. The mean age of the patients was 61 years with a median of 64 and range 46-82 years. The mean size of the tumour was 52 mm (range 22-100 mm). None of the patients had distant metastasis at presentation and only one case had local lymph node metastasis which had a carcinomatous appearance. Five women were still alive after a minimum 12-year follow-up period. Four patients died of their disease (three with lung metastasis only and one with lung and bone metastases), one died of carcinoma of the cervix and two patients were lost to follow-up. Pathologically, four cases (33.3%) had no or almost undetectable epithelial structures by light microscopy, i.e. "monophasic sarcomatoid carcinoma". The remaining cases revealed varying proportions of both epithelial and mesenchymal elements, i.e. "biphasic sarcomatoid carcinoma". Of the epithelial component, six (50%) tumours had predominantly carcinoma of no special type, one lobular and one tubular carcinoma. The mesenchymal component was fibromatosis/nodular fasciitis-like, malignant fibrous histiocytoma-like (MFH), osteosarcoma-like and fibrosarcoma-like in five (42%), four (33%), two (17%) and one (8%) tumours, respectively. In 3/4 monophasic tumours, the mesenchymal component was of a low-grade fibromatosis/nodular fasciitis type. In 6/12 (50%) of the cases there was associated in-situ atypical epithelial proliferation (five ductal carcinoma in situ (DCIS) and one atypical ductal hyperplasia). CONCLUSIONS: From this small series it appears that sarcomatoid carcinoma is an uncommon tumour, which is large in size and tends to lack local or distant metastasis at presentation. Pathologists should be alert to the presence of the bland monophasic sarcomatoid carcinoma which has a pure mesenchymal appearance on light microscopy, but epithelial components demonstrated by cytokeratin immunohistochemistry. These showed metastases on long-term follow-up, similar to other histological patterns of sarcomatoid carcinoma.     

Diffuse sclerosing variant of papillary thyroid carcinoma: A clinicopathologic and immunophenotypic analysis of 22 cases

Background: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon tumor making up about 2% of all papillary thyroid carcinomas. Previous studies have not comprehensively evaluated these tumors in a large series of patients. Design: Twenty-two cases of DSV-PTC diagnosed between 1970 and 2000 were identified in the files of the AFIP. Histologic and immunohistochemical features were evaluated and patient follow-up was obtained. Results: The tumors affected 14 females and 8 males, aged 6 to 49 yr (mean, 18 yr), with males presenting at a mean older age than females (24 vs 14 yr). Symptoms included an enlarging mass in the thyroid, present for a mean of 9.5 mo. While a dominant tumor was identified in a single lobe, bilateral disease was common (n=16). The dominant mass ranged in size from 1.7 to 5.8 cm in diameter (mean, 3.8 cm). Histologically, all cases demonstrated a papillary carcinoma (conventional, solid, or follicular pattern) diffusely involving the gland. Extrathyroidal extension, lymphocytic thyroiditis, squamous metaplasia, increased fibrosis/sclerosis, and psammoma bodies were present to a variable degree. Both the papillary carcinoma and squamous metaplasia cells were strongly immunoreactive with CK19, thyroglobulin, and TTF-1. An increased number of S-100 protein immunoreactive dendritic cells were recognized. p53 was increased (>15%) in the tumor cells in 12 patients, while Ki-67 was increased in the tumor cells in two patients. Perithyroidal and cervical lymph node metastasis occurred in 18 (82%) patients. All metastases demonstrated histologic features similar to the primary. Complete resection (thyroidectomy in 18 patients) with lymph node dissection, yielded a 95% 5-yr survival without evidence of disease. One patient died of disease after a malignant transformation of the squamous metaplasia into squamous cell carcinoma. Conclusions: The recognition of DSV-PTC can be made with the following features: classic to solid foci of PTC, lymphocytic thyroiditis, squamous metaplasia, increased fibrosis, and innumerable psammoma bodies. DSV-PTC is more biologically aggressive than conventional PTC, but the patients’ survival is not significantly different. This diagnosis should lead the clinician to aggressively manage these patients (thyroidectomy and lymph node dissection) in an effort to achieve an excellent long-term clinical outcome.     

Clinicopathological and Molecular Histochemical Review of Skull Base Metastasis from Differentiated Thyroid Carcinoma

Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma.     

肺大细胞神经内分泌癌的预后影响因素：一项基于SEER数据库的研究

目的:探讨肺大细胞神经内分泌癌（LCNEC）患者的生存预后及其影响因素。方法:横断面研究。纳入监测、流行病学和最终结果数据库（SEER）2010年1月—2016年12月收录的2 504例肺LCNEC患者,其中男1 357例、女1 147例,<60岁633例、60～80岁1 664例、>80岁207例。采用Kaplan-...     

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.     

Bcl-2 and p53 expression in insular and in well-differentiated thyroid carcinomas with an insular pattern

Expression of p53 and bcl-2 oncogenes was investigated in poorly differentiated, so-called insular carcinomas of the thyroid gland and also in the follicular and papillary carcinomas with an insular component. Hematoxylin-eosin sections of 217 thyroid carcinomas were reevaluated for insular carcinoma and also for thyroid carcinomas with an insular component. Immunohistochemical staining method was used for detecting p53 and bcl-2 expression on paraffin blocks of three pure insular, five follicular or papillary thyroid carcinomas with a major insular component (more than 50%) and six with a minor insular component (20–50%). Flow cytometry was also performed in these cases. None of the cases showed p53 immunoreactivity. Bcl-2 expression was observed in all cases and the most intense staining was seen in insular areas. All the cases were diploid. We suggest that bcl-2 plays a role in loss of differentiation of thyroid carcinomas.     

Thyroid carcinoma with papillary and squamous features: Report of a case with histogenetic considerations

We present a case of an 82-year-old female with a painless left latero-cervical swelling, which increased in size over the course of 6 months, compressing adjacent organs. The histopathological examination, following dissection of the left thyroid lobe and ipsilateral cervical lymph nodes, yielded two intermingled morphologically distinct histotypes that included conventional papillary thyroid carcinoma (PTC) and poorly differentiated squamous cell carcinoma (SCC) with cystic features. The clinical presentation, the immunophenotype, and the genotype, especially of the malignant squamous component with partial expression of TTF1, marked expression of p63 and mutation of BRAF, were consistent with the diagnosis of a papillary thyroid carcinoma with squamous component. The possibility of a squamous cell carcinoma of unknown origin metastasizing to a primary papillary thyroid carcinoma cannot be completely ruled out. This particular presentation of thyroid carcinoma carries a poor prognosis in 20% of cases, with high recurrence rates and distant metastasis.     

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.     

Metastasis from small cell carcinoma of the lung producing acute appendicitis

A case of acute gangrenous appendicitis with perforation caused by metastatic small cell carcinoma of the lung in a 65 year old man is reported. The manifestation of appendicitis occurred more than 4 years after the diagnosis of the bronchogenic carcinoma. With longer survival of patients with disseminated tumors it is probable that new manifestations of those malignancies will be discovered. Acute appendicitis due to metastasis from a distant neoplasm should be considered in the differential diagnosis of right lower abdominal pain in the oncology patient.     

The fibrotic focus in advanced colorectal carcinoma: a hitherto unrecognized histological predictor for liver metastasis

 A fibrotic focus (FF) is a clearly defined area consisting of fibroblasts and/or collagen fibres arranged in irregular or storiform patterns within tumours. We looked to see whether FF in advanced colorectal carcinoma was associated with distant organ metastasis especially to the liver. The correlation between FF and the presence of synchronous or total (synchronous and/or metachronous) liver metastasis and tumour recurrence was assessed in 77 patients with Dukes B and C advanced colorectal carcinoma treated by resection. The median follow-up period was 21 months. In multivariate analysis, FF significantly increased the relative risk (RR) of synchronous liver metastasis (RR=4.9, P<0.05) and total liver metastasis (RR=4.6, P<0.05). FF also increased the RR of tumour recurrence (RR=2.4), but the increase was not statistically significant. FF is a newly recognized histological indicator of liver metastasis in advanced colorectal carcinoma. Received: 26 March 1998 / Accepted: 20 July 1998     

Analysis of clinical outcomes of patients with adenoid cystic carcinoma of Bartholin glands

Adenoid cystic carcinoma of Bartholin glands (BG-ACC) is a rare, slow-growing but a highly aggressive tumor with remarkable capacity for local recurrence and distant metastasis. The purpose of this study was to elucidate our experiences of the diagnosis and treatment of BG-ACC and to analyze the clinical outcomes and prognosis of patients with BG-ACC. A retrospective chart review was performed to assess the demographic information, chief complaints, pathologic features of tumors, primary treatment, and development of local recurrence or distant metastasis, as well as the patient outcome. All patients received surgical excision as the primary treatment, and the diagnosis of BG-ACC was confirmed histopathologically. Three of four patients whose tumors showed pathologic features indicating a high probability of recurrence received adjuvant radiotherapy. These patients did not develop local recurrence, in contrast, one patient who did not receive adjuvant radiotherapy developed local recurrence and distant metastasis on several occasions. All patients who received primary surgical treatment are alive to date. When patients who are more than 40 years of age and who present with symptomatic BG lesions, BG-ACC should be included in the differential diagnosis and biopsy should be performed for histopathologic confirmation. Radical local excision with sufficient negative margins seems to be beneficial for primary treatment. Adjuvant radiotherapy is a reasonable treatment option for patients with high risk factors after surgery or for patients who develop local recurrence.     

Differentiated thyroid carcinomas with vascular invasion: a comparative study of follicular,Hürthle cell and papillary thyroid carcinoma

AIM: Non-medullary thyroid carcinomas arise from follicular cells. The purpose of this study is to correlate clinical and pathological properties of these tumours with the rate of distant metastasis from a series of thyroid tumours excised at one institution. METHODS: A total of 311 non-medullary thyroid tumours were identified and divided into: 29 follicular carcinoma (FC), 12 Hürthle cell carcinoma (HC), 13 Hürthle cell papillary thyroid carcinoma (HPTC) with vascular invasion (VI), 32 papillary thyroid carcinoma (PTC) with VI and 225 PTC without VI. The mean follow-up was 6.5 years with a range of 1-17 years. The tumours were histologically subdivided into minimal or wide invasion for FC and HC and focal or extensive invasion for PTC and HPTC, and stratified according to status of VI. RESULTS: The rate of distant metastasis was similar for FC, malignant Hürthle cell tumours and PTC with VI, and increased with extent of invasion. VI was seen in 12% of all PTC and 0% of HPTC in this study. PTC without VI were associated with a much lower potential of distant metastasis, were smaller in size and occurred in patients of younger age than PTC with VI. In addition, there was a tendency for increased potential for distant metastases with increased tumour size and patient age for all groups of tumours in the study. Patient age and tumour size appeared to play a smaller role than that of VI in predicting distant metastasis. CONCLUSIONS: Our study suggests that the rate of distant metastasis relates to VI, patient age and tumour size, regardless of Hürthle cell, FC or PTC differentiation. PTC of large size, and in patients older than 45 years, have a high propensity for vascular invasion.     

喉癌组织淋巴管生成与其转移和患者预后的关系

目的：探讨喉癌组织的淋巴管生成与其肿瘤转移及患者临床预后间的可能联系。方法：采用免疫组织化学方法(IHC)对60例喉癌组织进行淋巴管内皮细胞透明质酸受体l(LYVE-1)特异性染色,并对淋巴管计数,进一步分析淋巴管密度(LVD)与患者临床病理及预后间的关系。结果：喉癌组织LYVE-l染色LVD为14.98±5.12,明显高于癌旁正常组织(6.76±3.01)(P<0.001);分层分析示喉癌组织LVD与患者年龄、性别、分化程度、临床分型和远隔转移无关(P>0.05),与淋巴结转移和肿瘤分期密切相关(P<0.05);高LVD组患者5年生存率为23.3%,低LVD组5年生存率为66.7%,两组5年生存率有统计学意义(P<0.001);进一步Cox生存风险模型分析示,肿瘤分期和LVD可能是影响喉癌患者5年临床预后的独立因素(均P<0.05)。结论：喉癌淋巴管生成可能参与淋巴结转移等过程,且LV D可能是影响患者临床预后的独立因素。     

Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.

BACKGROUND. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). METHODS. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. RESULTS. Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). CONCLUSIONS. The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.