Thyroid sarcoidosis: a rare entity in the differential diagnosis of thyroid cancer.

SUMMARY: We present two cases of thyroid sarcoidosis that were misdiagnosed as thyroid cancer. In the first patient, fine needle aspiration cytology (FNAc) of a suspicious thyroid nodule indicated the presence of papillary thyroid cancer, and the patient underwent thyroid surgery. However, histopathology identified a sarcoid granuloma, without any sign of malignancy. The second patient had a history of papillary microcarcinoma with suspicious lymph nodes diagnosed years after the initial diagnosis and was referred for assessment of cervical lymphadenopathy. Fine needle aspiration cytology (FNAc) of the suspicious lymph nodes erroneously indicated metastasis from thyroid cancer, and lateral modified lymph node dissection was performed, based on FNAc and ultrasonographic features. Histopathology excluded malignancy and identified non-caseating granulomas. Sarcoidosis of the thyroid may have a clinical presentation similar to well-differentiated thyroid carcinoma and, although rare, should be considered in the differential diagnosis, especially when other signs of the disease are already present. In these cases, FNAc provided a false diagnosis of papillary thyroid carcinoma and lymph node metastases that led to unnecessary surgery. LEARNING POINTS: Sarcoidosis may share clinical and ultrasonographic features with papillary thyroid carcinoma. Fine needle aspiration cytology is helpful in the diagnosis of both conditions; however, the overlapping cytological characteristics may lead to erroneous diagnosis. The present cases illustrate the importance of cytological identification of these difficult cases. Every piece of information provided by the clinician is essential to the cytologist.

Intrathyroidal parathyroid adenoma mimicking thyroid cancer.

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia; patients are usually asymptomatic and the cause in 80-85% of cases is a single parathyroid adenoma (PA). Parathyroid adenomas arise from clonal expansion of tumor cells and may be located either posteriorly to the thyroid lobes or in ectopic sites. The incidence of intrathyroidal PAs varies from 1% to 6% and although uncommon, they pose certain diagnostic difficulties which may complicate treatment. The identification of the adenoma requires a combination of clinical evidence, imaging information and cytological findings due to the challenging distinction between thyroid and parathyroid lesions. We present the case of a patient with a large, partially cystic intrathyroidal parathyroid adenoma which was initially identified as a malignant thyroid nodule. We discuss the caveats that present in these rare cases and the important clinical and histological features that aid in the final diagnosis. In the case of our patient the cytological similarities between thyroid malignant cells and parathyroid cells, in combination with the negative sestamibi scan, resulted in a more invasive surgery than that a single parathyroid adenoma would require. Clinicians need to be vigilant in terms of the similarities between parathyroid and thyroid cytology in order to provide optimal patient care in these rare cases.

PAK1 Expression in Pancreatic Cancer: Clinicopathological Characteristics and Prognostic Significance.

BACKGROUND: Improvement of the management of pancreatic cancer requires a better understanding of the genetic and molecular changes responsible for the development of the disease. The family of p21-activated kinases (PAKs) and especially PAK1 appears to mediate many cellular processes that contribute to the development and progression of pancreatic cancer, but the clinical relevance of PAK1 expression with the disease still remains unclear. Aim of the study was to assess the clinical value and the potential prognostic significance of PAK1 in pancreatic adenocarcinoma. METHODS: We investigated the relationship between the PAK1 expression and the clinical and histopathologic characteristics of pancreatic cancer patients and the potential significance of PAK1 on survival. We examined tissue samples from 51 patients operated for pancreatic cancer. PAK1 expression was investigated with immunohistochemistry and correlated to clinicopathological parameters. RESULTS: PAK1 was detected in all tumor samples and high expression was found in most patients. High PAK1 expression was also associated with younger age and well-differentiated tumors, but no association was found between PAK1 expression and Tumor-Node-Metastasis stage as well as deceased or alive status on follow-up. Moderate to high PAK1 expression favored higher 6-month and 1-year survival and low PAK1 expression 2-year survival but without statistical significance. CONCLUSIONS: Our results indicate that PAK1 could potentially be used as a prognostic marker in pancreatic cancer. Further studies could clarify whether utilization of PAK1 in therapeutic protocols for the treatment of pancreatic cancer will render them more effective.

Malignant peripheral nerve sheath tumor (MPNST) arising from angiosarcoma: a rare case report.

PURPOSE: An extremely rare case of divergent differentiation of a cutaneous angiosarcoma to a malignant peripheral nerve sheath tumor (MPNST) is presented. METHODS: A 62-year-old male patient presented with an angiosarcoma of the left buccal region, which was excised with wide surgical margins. Four months after the operation, the tumor recurred locally as a MPNST. The recurrent tumor was treated with surgical excision followed by postoperative radiotherapy. Four years later, the patient presented with solitary lung metastasis. The patient underwent upper right lobectomy. RESULTS: The patient is alive and disease-free 2 years after the lobectomy and 6 years after initial presentation. CONCLUSIONS: Divergent differentiation of an angiosarcoma to a neurosarcoma supports the theory that cells of the neural crest capable of differentiating both to neuroectoderm and to mesenchyme give origin to these tumors.

The Immunohistochemical Expression MTA 1 Protein and its Prognostic Value in Pancreatic Cancer.

Purpose/aim: To examine with immunohistochemical assay MTA1 protein expression levels in pancreatic cancer tissues defining its prognostic value. MATERIAL AND METHODS: The specimens derived from 51 patients who underwent surgery. The levels of MTA1 protein were compared with the age of the patients, their survival, and prognosis. Also, we studied clinical and histopathological factors such as the degree of tumor differentiation and its stage in correlation with MTA1 protein levels. In parallel, there was correlation between the expression of the ΜΤΑ1 protein and the aforementioned factors regarding survival rate. Furthermore, we independently correlated the patient's survival in relation to whether they had undergone adjuvant chemotherapy or not. RESULTS: It has been found to be low, moderate, or high expression of MTA1 levels in 48 out of 51 cancer tissues. Specifically, 49.0% of patients had low expression, 33.3% moderate, and 11.8% high expression of MTA1. Regarding the expression of MTA1 protein in correlation with various clinical and histopathological factors, a statistically significant correlation was observed with the degree of differentiation (p = 0.0068) and with the stage of the disease (p = 0.0173), but not with survival (p = 0.0740) or the age of them (p = 0.1547). Finally, it was found that overexpression of the MTA1protein is a prognostic factor for shorter survival in patients with pancreatic cancer (average 4.67 ± 0.95 months). CONCLUSIONS: MTA 1 protein may constitute an important prognostic marker in pancreatic cancer and could improve prognosis and treatment.

Co-expression of galectin-3 and CRIP-1 in endometrial cancer: prognostic value and patient survival.

Endometrial cancer is the sixth most common cancer in women. Galectin-3 (GAL-3) and CRIP-1 are multifunctional proteins which seem to be involved in many neoplasias. This study aims to point out correlations between clinicopathological findings and endometrial cancer patient survival to GAL-3 and CRIP-1 expression in order to enfold their diagnostic/prognostic potential. Tissues from 46 patients diagnosed with endometrial cancer were studied by immunohistochemistry, using monoclonal antibodies for GAL-3 and CRIP-1, and expression levels were correlated with clinicopathological findings and survival. Analysis was performed at single protein level or as co-expression. High expression of GAL-3 and CRIP-1 was independently associated with tumor depth and histological grade, respectively. Also, there was a significant correlation between high co-expression of the two proteins and the histological grade (aOR 2.66), the tumor depth (aOR 0.32) and the histological type (aOR 1.32), but not with the patients' age. Moreover, high expression of both proteins was observed in patients with shorter survival times. Interestingly, the co-expression of the two proteins exhibited some degree of monotony (Spearman's ρ = 0.768), indicating a common molecular pathway. This study provides evidence for a prognostic clinical potential of the combined study of GAL-3 and CRIP-1 in endometrial cancer. These factors are poorly studied in endometrium, and their role in the carcinogenetic process and on effective therapy awaits further elucidation.

Gonadotropin-releasing hormone neuropeptides and receptor in human breast cancer: correlation to poor prognosis parameters.

Expression of the two gonadotropin-releasing hormone homologue peptides GnRHI and GnRHII and their receptor GnRHR has been demonstrated in a number of malignancies. In hormone-dependent breast cancer, GnRH analogs are used for therapy in premenopausal women. Gene expression of GnRHI, II and R was studied in breast biopsies from primary breast adenocarcinoma obtained from the tumor and the adjacent benign tissue. Levels were evaluated by a multiplex real-time RT-PCR. GnRHI transcripts were detected in 14.7% of the benign and 29.4% malignant biopsies and GnRHII in 21.2% benign and 44.1% malignant biopsies. GnRHR was also more frequent in the malignant (54.2%) than in the benign (24.0%) biopsies, at similar expression levels. No transcripts were detected in biopsies from healthy individuals. There was a strong correlation between the presence of GnRHI and GnRHII transcripts and their receptor in the benign and the malignant biopsies. GnRHI, II and R expression correlated significantly with poor prognosis pathological parameters. Immunohistochemistry for GnRHR revealed expression in malignant cells and in epithelial cells of mammary ducts of the adjacent area with pre-cancerous features. In contrast, GnRH I and II peptides were rarely expressed at low levels in breast cancer cells. In conclusion GnRH peptides and receptor are expressed more frequently in breast tumors than in the adjacent mammary tissue, representing a malignant feature. Their expression correlated to tumor characteristics of poor prognosis and was therefore related to more aggressive malignancies. Concomitant expression of peptides and receptor supports an autocrine/paracrine regulating role.

The Immunocytochemistry Is a Valuable Tool in the Diagnosis of Papillary Thyroid Cancer in FNA's Using Liquid-Based Cytology.

Introduction. Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid. An accurate cytological diagnosis is based on distinctive cytological features in combination with immunocytochemistry. Methods. A number of 83 fine needle aspirations, positive for papillary thyroid cancer (44 from thyroid nodules and 39 from cervical lymph nodes), were studied using Thin Layer Cytology. A panel of the immunomarkers Cytokeratin-19, Galectin-3, HBME1, CD-44, CD-56, and E-Cadherin was performed. Results. Positive expression of CK-19 was observed in 77 cases (92.7%), of Galectin-3 in 74 cases (89.1%), of HBME1 in 65 (78.3%), and of CD-44 in 72 cases (86.7%). Loss of expression of CD-56 was observed in 80 cases (96.4%) and of E-cadherin in 78 (93.9%). Conclusions. Our data suggest that Thin Layer Cytology increases the diagnostic accuracy in papillary carcinoma and seems to be a promising technique for further investigation of thyroid lesions permitting the possibility to use archive material. Positive immunoexpression of CK-19, Galectin-3, HBME-1, and CD-44 improves the diagnostic accuracy of papillary thyroid cancer. Furthermore, loss of E-cadherin and of CD-56 expression is a feature of malignancy.

Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): prognostic value and survival of endometrial cancer patients.

AIM: The purpose of this study was to investigate the co-expression of survivin, c-erbB2, and COX-2 in endometrial cancer tissues and evaluate its prognostic significance in endometrial cancer METHODS: Tumor tissue biopsies from 110 patients with primary untreated endometrial carcinomas were studied by immunohistochemistry. Statistical analysis evaluated correlation of antigen expression with tumor stage, grade, myometrial invasion, and histologic type. Association with disease outcome was also investigated RESULTS: The results showed that expression of the three antigens was independently associated with histological grade, disease stage, and myometrial invasion. Clinicopathological parameters were also associated with the number of antigens expressed by each tumor, the expression of more antigens correlating with advanced stage disease and deep myometrial invasion. In a 10-year follow-up, patients with tumors expressing more of these three antigens had significantly lower survival rate that those with smaller expression score CONCLUSIONS: Our results indicate that the co-expression score has independent prognostic value for endometrial cancer.

Cervical masses as manifestation of papillary thyroid carcinomas

BACKGROUND: Papillary thyroid microcarcinomas are tumors often found accidentally after thyroidectomy for other thyroid disorders. METHODS: Patients with enlarged lateral cervical masses, with unknown thyroid disease, found to have metastases from papillary thyroid carcinoma

Primary mediastinal liposarcoma: a case report.

INTRODUCTION: Liposarcoma is the most commonly diagnosed soft tissue sarcoma in adults and occurs predominantly in the lower limbs and retroperitoneum. Primary mediastinal liposarcomas are rare.They are often asymptomatic and when growing to large size the presenting symptoms are related to direct invasion or compression of other thoracic organs such as the heart, great vessels and lung. CASE PRESENTATION: A case of a 68-year-old man with primary mediastinal liposarcoma involving the diaphragm and pericardium and successfully managed by complete surgical excision is presented. The patient's postoperative course was uneventful with no evidence of recurrence 9 months after the operation. CONCLUSION: Surgical removal is the optimal treatment for a mediastinal liposarcoma. If the entire tumor can not be resected, surgical debulking often results in symptomatic relief. International literature has demonstrated that recurrent disease occurs and therefore a long-term careful follow up is required.

Cytoplasmic expression of c-erb-B2 in endometrial carcinomas.

BACKGROUND: The aim of this study was to investigate the expression of c-erb-B2 in endometrial cancer with attention to both membranous and cytoplasmic staining, and to elucidate the significance of cytoplasmic signaling. MATERIALS AND METHODS: c-erb-B2 reactivity was assessed by immunohistochemistry in 110 patients using a polyclonal antibody, and evaluated semiquantitatively according to the percentage of cells demonstrating membranous or diffuse cytoplasmic staining. Correlation was made with tumor stage, grade, myometrial invasion, histologic type, and disease outcome. RESULTS: c-erb-B2 overexpression, indicated by membranous and cytoplasmic staining of at least 10% of the tumor cells, was found in 47 (42.7%) cases. Cytoplasmic expression of c-erb-B2 was observed more frequently than membranous (69.1 vs. 5.5%). Synchronous cytoplasmic and membranous signaling was noticed in 7.9% of cases. Interestingly, patients with cytoplasmic c-erb-B2-positive tumors had a significantly shorter survival (p = 0.047). CONCLUSIONS: These results indicate that c-erb-B2 is a specific marker of endometrial cancer. It is also an independent prognostic indicator of poor outcome. Cytoplasmic staining is as important as membranous staining, and is also a specific finding.

Unusual localization of an adenoid cystic carcinoma subsequent to superficial parotidectomy for a benign lesion.

Adenoid cystic carcinoma of the parotid gland is relatively rare. According to a retrospective study of the medical records and histopathology files of 514 cases of parotid tumors operated at our hospital over a period of 18 years, adenoid cystic carcinoma represented only 2.3% of all parotid gland neoplasms, a total of 12 cases. In our records we retrieved only one documented case of adenoid cystic carcinoma that originated in the parotid gland subsequent to superficial parotidectomy for a benign lesion (pleomorphic adenoma). An even more exceptional presentation of adenoid cystic carcinoma is as a bilobed tumor extending from the post auricular to the temporal and zygomatic region. The management of this case is presented along with a brief review of the literature concerning the evaluation and management of this rare entity.

Concurrent primary Hodgkin's lymphoma and recurrent pleomorphic adenoma of the ipsilateral parotid gland: report of a rare case.

The synchronous occurrence of two histologically different and morphologically distinct tumours in a single parotid gland is an exceptionally rare and probably coincidental event. We have recently experienced such a case initially suspected of being a recurrent pleomorphic adenoma. Superficial parotidectomy, however, revealed two separate masses. Postoperative histopathological examination diagnosed the presence of a pleomorphic adenoma with a concurrent primary parotid gland Hodgkin's lymphoma arising from an intraglandular lymph node. The management of this case is presented along with a brief review of the literature concerning the evaluation and management of this rare entity.

Use of a thin-layer technique in thyroid fine needle aspiration.

OBJECTIVE: To investigate the efficacy of the ThinPrep Processor (Cytyc Corporation, Boxborough, Massachusetts, U.S.A) in fine needle aspiration (FNA) of thyroid gland lesions. STUDY DESIGN: This study included 459 thyroid FNA specimens obtained from patients who came to our endocrinology department with various thyroid disorders over 3 years. The cytologic material was prepared using both the conventional and ThinPrep method in the first 2 years (285 cases), while in the last one only the ThinPrep method was used (1 74 cases). The smears were stained using a modified Papanicolaou procedure and May-Grünwald-Giemsa stain. Immunocytochemistry was performed on thin-layer slides using specific monoclonal antibodies when needed. Thin-layer and direct smear diagnoses were compared with the final cytologic or histologic diagnoses, when available. RESULTS: Our cases included 279 adenomatoid nodules, 15 cases of Hashimoto thyroiditis, 45 follicular neoplasms, 14 Hürthle cell tumors, 58 papillary carcinomas and 1 5 anaplastic carcinomas. Thin-layer preparations showed a trend toward a lower proportion of inadequate specimens and a lower false negative rate. Cytomorphologic features showed some differences between the 2 methods. Colloid was less frequently observed on ThinPrep slides, while nuclear detail and micronucleoli were more easily detected with this technique. Moreover, ThinPrep appeared to be the appropriate method for the use of ancillary techniques in suspicious cases. CONCLUSION: Thin-layer cytology improves the diagnostic accuracy of thyroid FNA and offers the possibility of performing new techniques, such as immunocytochemistry, on the same sample in order to detect malignancy as well as the type and origin of thyroid gland neoplasms.

Mediastinum thymoma diagnosed by FNA and ThinPrep technique: a case report.

Thymoma is a primary tumor of the thymus epithelial cells. It may be asymptomatic or accompanied with atypical clinical symptoms or paraneoplastic syndromes, such as myasthenia gravis. The biological behavior of thymomas is unpredictable. The invasion of the capsule or the adjacent tissues is the major diagnostic criterion for the malignant behavior of these tumors. This is an interesting case of thymoma diagnosed by fine-needle aspiration biopsy (FNA) and ThinPrep technique, in a 54-year-old female patient with a history of gastric adenocarcinoma. Cytology of the mediastinum mass revealed a mixed population of epithelial cells and lymphocytes. The tumor was excised and the histopathological examination supported the cytological diagnosis. Thymomas commonly constitute a problem in differential diagnosis of mediastinum masses. FNA biopsy in correlation with ThinPrep technique and immunocytochemistry may play a significant role in clarifying the nature of these lesions and may contribute to the early management and choice of the optimal therapeutic manipulation.

Brooke-Spiegler syndrome with parotid gland involvement.

Salivary gland involvement in Brooke-Spiegler syndrome (BSS), an autosomal dominantly inherited disease, is known though not frequent. A case of familial cylindromatosis with parotid gland adenoma is herein reported. A 67-year-old lady presented with multiple scalp nodules and papular coalescent lesions over the nasolabial folds and the forehead. The clinical examination also revealed a left preauricular lump. Multiple biopsies of the scalp lesions and the nasolabial papules revealed cylindromas and trichoepitheliomas respectively. CT scan and FNA of the preauricular lump were suggestive of parotid gland adenoma. The patient underwent excision of the scalp cylindromas and total left parotidectomy. There is no evidence of recurrence after 4 years. The association of BSS with salivary gland tumours, emphasizes the necessity of thorough salivary gland examination in all patients with skin lesions. Knowledge of the genetic background of BSS allows for genetic counseling of patients.