Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications.

Carcinoma of the thyroid gland, the most frequently diagnosed endocrine malignancy, is often associated with early regional metastases. With the exception of papillary carcinoma, distinguishing benign from malignant thyroid neoplasms in the absence of metastatic disease is difficult. Recently, the vertebrate lectins galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation of a variety of tissues. To determine whether these galectins have a role in thyroid neoplasia, we analyzed 32 specimens from thyroid malignancies (16 papillary, 7 follicular, 8 medullary carcinomas, and 1 metastasis to lymph node), 10 benign thyroid adenomas, 1 nodular goiter, and 33 specimens from adjacent normal thyroid tissue for the expression of galectin-1 and galectin-3 with immunohistochemical and immunoblotting techniques utilizing anti-galectin antibodies. All thyroid malignancies of epithelial origin (ie, papillary and follicular carcinomas) and a metastatic lymph node from a papillary carcinoma expressed high levels of both galectin-1 and galectin-3. The medullary thyroid carcinomas, which are of parafollicular C cell origin, showed a weaker and variable expression of these galectins. In contrast, neither benign thyroid adenomas nor adjacent normal thyroid tissue expressed galectin-1 or galectin-3. These results suggest that galectin-1 and galectin-3 may be associated with malignant transformation of thyroid epithelium and may potentially serve as markers for distinguishing benign thyroid adenomas from differentiated thyroid carcinomas.     

Pathomorphology of thyroid gland lesions associated with radiation exposure: the Chernobyl experience and review of the literature.

The common sources of ionizing radiation exposure to the thyroid gland in humans are accidental environmental exposure and medical, therapeutic, or diagnostic irradiation. Radiation often induces notable histologic changes in the thyroid tissue and is a well-established risk factor for benign and malignant thyroid tumors. In this paper, we review the acute and chronic histologic changes in the thyroid gland subjected to irradiation, and characterize benign thyroid nodules and malignant tumors arising after exposure, with particular emphasis on thyroid lesions in the population exposed to ionizing radiation as a result of the Chernobyl nuclear accident.     

Diagnostic challenges in thyroid cytopathology

Fine needle aspiration (FNA) is a long-standing modality used to obtain diagnostic material from patients with thyroid nodules. However, some common and uncommon situations exist in which diagnostic categorization of an FNA specimen is not straightforward. Diagnostically challenging thyroid lesions are typically either benign entities with cytomorphology that mimics malignancy, or malignant entities with unusual cytomorphology that causes difficulty in classification. Awareness of such diagnostic challenges can help broaden one's differential diagnosis when encountering such lesions on FNA. However, in many instances a definitive diagnosis may not be possible and providing an indeterminate diagnosis is most appropriate.     

Combined Riedel's Disease and Fibrosing Hashimoto's Thyroiditis: A Report of Three Cases with Two Showing Coexisting Papillary Carcinoma

Extensive sclerosis of the thyroid gland can be seen in both benign and malignant conditions. The benign sclerosing lesions of the thyroid include Riedel’s disease and fibrosing Hashimoto’s thyroiditis. Although these conditions usually occur separately, rarely can they occur simultaneously. In malignant lesions, papillary thyroid carcinoma and anaplastic carcinoma of the thyroid can be associated with extensive sclerosis leading to partial or total effacement of the tumor. We report on three cases that showed simultaneous occurrence of Riedel’s disease and fibrosing Hashimoto’s thyroiditis. Two of these cases also showed papillary carcinoma (one case of Warthin’-like papillary carcinoma and one case of classic type). All patients were females (age range 32–67 yr) and presented with elevated antithyroglobulin antibodies. Two patients presented with a solitary thyroid mass, and from these one had multiple bilateral neck nodes and a paravertebral mass. The third patient presented with a multinodular gland adherent to neck structures. All patients underwent total thyroidectomy. Histologic sections showed extensive replacement of the thyroid parenchyma with dense keloidal fibrosis, intermixed well-developed lymphoid follicles, and scattered lymphocytes and plasma cells. In all cases the fibrotic process extended beyond thyroid capsule with involvement of the perithyroidal soft tissues and skeletal muscle consistent with Riedel’s disease. One case showed a classic papillary carcinoma with bilateral lymph node metastases, and the other showed a Warthin’s-like papillary carcinoma. In both cases the papillary cancers were surrounded by dense sclerosis. Immunohistochemical stains for B- and T-markers and immunoglobulin light chains showed a polyclonal population of the lymphoid cells. The simultaneous occurrence of Riedel’s disease and fibrosing Hashimoto’s thyroiditis is rare and most likely represents a coincidental phenomenon, because both of these conditions are distinct clinicopathologic entities.     

Acral soft tissue tumors: a review

Acral soft tissue tumors may present significant diagnostic challenges both for the pathologist and the clinician. This review discusses the most common benign and malignant entities that characteristically present in an acral location. Clinical, histologic, and immunohistochemical features are discussed along with prognosis and differential diagnosis.     

Benign salivary gland tissue inclusion in a pulmonary hilar lymph node from a patient with invasive well-differentiated adenocarcinoma of the lung: a potential misinterpretation for the staging of carcinoma

Benign epithelial and nonepithelial inclusions have been found in lymph nodes in multiple body sites. These inclusions have been seen in cervical, axillary, mediastinal, abdominal, and pelvic lymph nodes. They appear as benign epithelial, parathyroid, decidual, mesothelial, angiolipomatous, nevus cells, or Tamm-Horsfall protein. Although heterotopic salivary gland tissue is not infrequent in paraparotid lymph nodes, it has only been described in lymph nodes of the pulmonary hilum once. A 68-year-old woman with gastric lymphoma now in remission presented for routine follow-up and was found to have a lung mass. After a fine needle aspiration biopsy diagnosis of adenocarcinoma, lobectomy and lymph node dissection were performed. Histological sections of lung demonstrated a well-differentiated adenocarcinoma and one lymph node, which displayed a subcapsular nest of well-formed salivary glands occupying approximately one third of the nodal tissue. The inclusion was composed of acinar cells of both serous and mucinous types, but ductal type of cells were not seen. Identification of heterotopic tissue in lymph nodes is of great importance for patient management. Misdiagnosing benign glandular inclusions for metastasis could potentially lead to incorrect tumor staging. Benign salivary gland tissue inclusions should be considered in the differential diagnosis when evaluating for metastatic adenocarcinoma. The salivary gland inclusion in pulmonary hilar lymph node may be histogenetically related to the minor salivary glands, which are located within the bronchial submucosa.     

涎腺细针吸取细胞学分类诊断价值和存在问题

目的 分析涎腺疾病细针吸取细胞学（FNAC）形态学特点和准确分类,探讨涎腺FNAC的诊断价值和存在问题。方法 回顾113例涎腺FNAC形态学特征、免疫表型和分类诊断,并结合临床、组织病理学分析。结果 FNAC失败2例,诊断非肿瘤12例、肿瘤99例（良性肿瘤82例,恶性17例）。富于细胞多形性腺瘤、腺样囊性癌和基底细胞腺瘤相似,鉴别诊断困难。腮腺淋巴上皮癌与未分化型鼻咽型鳞状细胞癌转移完全一致,鉴别需结合临床分析。与组织学比较发现,FNAC误诊3例,分别为淋巴结反应性增生疑为非霍奇金淋巴瘤、黏液表皮样癌诊为“少量异型细胞”和淋巴上皮癌疑为良性淋巴上皮病变。FNAC区分良、恶性准确率97．4％（110／113）,良性病变99．0％（95／96）,恶性肿瘤88．2％（15／17）。总体分类准确率90．3％（102／113）,特异性91．9％（102／111）;良性病变准确率91．7％（88／96）,特异性92．6％（88／95）;恶性肿瘤准确率82．4％（14／17）,特异性87．5％（14／16）。结论 FNAC诊断涎腺良、恶性病变敏感、可靠,可提供准确的分类诊断,但诊断某些肿瘤仍有局限性,需要活检证实。     

Neoplastic human tissue mast cells express the adhesion molecule CD44/HCAM

Expression of the homing-associated cell adhesion molecule/HCAM (CD44) in normal/reactive and neoplastic human tissue mast cells (TMC) was determined immunohistochemically using the antibody DAKO-DF1485, which detects all isoforms of CD44. Studies were performed on 30 routinely processed specimens. Twenty of these, from bone marrow, skin, spleen, liver, lymph node and jejunal mucosa, contained infiltrates of TMC. These represented various types of generalized mastocytosis/systemic mast cell disease, including benign systemic mastocytosis, malignant mastocytosis and cutaneous mastocytosis. Ten specimens consisted of tissue with a marked reactive increase in TMC; most of these were lymph nodes with chronic nonspecific lymphadenitis and benign or malignant solid tumours. In all 30 specimens TMC exhibited an annular pattern of immunostaining, which was usually very strong. Both normal/reactive and neoplastic TMC exhibited consistent immunoreactivity with the antibody DAKO-DF1485, and this antibody may be of diagnostic value in the detection of atypical TMC associated with malignant mastocytosis. TMC and their neoplastic derivatives belong to a large family of mesenchymal and epithelial cells containing the principal surface receptor for hyaluronan.     

S100A4蛋白在甲状腺癌中的表达和意义

 目的 探讨S100A4蛋白在甲状腺癌组织中的表达及临床意义。方法 应用免疫组织化学SP法,检测56例甲状腺癌（乳头状腺癌30例,髓样癌12例,滤泡状癌8例,未分化癌6例）、45例甲状腺良性病变（甲状腺腺瘤、结节性甲状腺肿、原发性甲状腺功能亢进各15例）及13例甲状腺癌癌旁正常组织中S100A4蛋白的表达水平。结果 甲状腺癌组织中S100A4蛋白表达阳性率为83.9%（47/56）,表达强度呈（+）者25例,（++）者12例,（+++）者10例;甲状腺良性病变组织中S100A4蛋白表达阳性率为11.1%（5/45）,表达强度均为（+）;癌旁正常甲状腺组织中S100A4蛋白表达均呈阴性。甲状腺癌组织与后两者比较,差异均具有统计学意义（P<0.01）。临床分期Ⅰ～Ⅱ期者S100A4蛋白表达阳性率为77.8%（28/36）,表达强度为（+）者22例,（++）者4例,（+++）者2例;临床分期Ⅲ～Ⅴ期者表达阳性率为95.0%（19/20）,表达强度为（+）者3例、（++）者8例、（+++）者8例;两者间差异有统计学意义（P<0.01）。有淋巴结转移者S100A4蛋白表达阳性率为100%（16/16）,表达强度为（++）者8例、（+++）者8例;无淋巴结转移者表达阳性率为77.5%（31/40）,表达强度为（+）者25例、（++）者4例、（+++）者2例;两者间差异有统计学意义（P<0.01）。不同病理类型甲状腺癌组织中S100A4蛋白表达阳性率和表达强度差异无统计学意义（P>0.05）。结论 S100A4蛋白表达与甲状腺肿瘤细胞的恶性增殖和侵袭转移密切相关。S100A4蛋白表达强度作为判断甲状腺癌的恶性程度及预后的检测指标,具有临床应用的价值。     

Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) immunoexpression in follicular-patterned lesions of the thyroid gland

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein which participates in iron trafficking and which is involved in cancerogenesis and cancer progression. Since its over-expression has been documented in thyroid malignancies in comparison to thyroid normal gland, in the present study, we aimed to determine whether the evaluation of NGAL immunoexpression may be of help in the differential diagnosis of follicular-patterned thyroid lesions. Our additional aim was to test the possible interference of endogenous biotin on the immunohistochemical findings. Thus, all the immunohistochemical procedures, carried out with labeled streptavidin biotin method, were doubly performed, with or without the preliminary inhibition of endogenous biotin. No NGAL staining was found in the normal thyroid gland nor in the nodular colloid goiters or in Hashimoto's thyroiditis. NGAL expression appeared to be significantly more frequent in the malignant tumors in comparison to benign ones (P < 0.000001). Even more, NGAL expression appeared to be specific (specificity 93%) for carcinoma and represented a sensitive method (sensitivity 84%), with high negative (88%) and positive (94%) predictive values, as well as high diagnostic accuracy (88%), in the identification of follicular-patterned thyroid malignant tumors. The specificity, positive predictive value and diagnostic accuracy lowered when biotin was not preliminary inhibited, due to the presence of false positives among benign Hürthle cell tumors. In conclusion, the immunohistochemical detection of NGAL may be helpful in the differential diagnosis between malignant and benign follicular-patterned lesions of the thyroid. The use of biotin free system or the preliminary biotin inhibition is warranted for the detection of NGAL in thyroid samples, especially when dealing with Hürthle cell tumors.     

Fine-needle aspiration of spindle cell and mesenchymal lesions of the salivary glands

Fine-needle aspiration (FNA) biopsy can accurately diagnose epithelial lesions of the salivary gland. Its role in the evaluation of salivary gland lesions containing a significant spindle cell component is less clear. We describe the cytologic features of 25 spindle cell lesions of the salivary gland and discuss the differential diagnosis and potential diagnostic pitfalls. Twenty-five aspiration smears (3.0%) containing a significant spindle cell or mesenchymal component were identified out of 844 salivary gland FNAs performed over a 5-year period. These aspiration smears were from 25 patients. The smears were classified into three categories: 1) reactive or inflammatory conditions, including one granulation tissue and four granulomatous sialoadenitis; 2) benign neoplasms, including one schwannoma, one fibromatosis, four lipomas, and nine pleomorphic adenomas; 3) malignant neoplasms, including one recurrent malignant fibrous histiocytoma (MFH), two metastatic melanomas, and two metastatic osteosarcomas. There was one false-negative biopsy. The metastatic desmoplastic malignant melanoma was initially interpreted as a reactive lymph node with fibrosis. A specific diagnosis was rendered in 21 (84%) cases. The schwannoma was diagnosed cytologically as benign spindle cell lesion, not otherwise specified (NOS), fibromatosis as an atypical cellular proliferation, and MFH as poorly differentiated malignant neoplasm. Salivary gland lesions with a significant spindle cell component are rarely encountered on FNA and constitute a heterogeneous group. A specific diagnosis can be rendered in the majority of cases by correlating clinical and cytologic findings.     

Thyroid implants after surgery and blunt trauma

The differential diagnosis of thyroid tissue found laterally in the neck includes several conditions: lymph node deposits of thyroid carcinoma, "benign metastatic thyroidosis," detached thyroid nodules, and true ectopic thyroid tissue. We have studied nine cases with thyroid deposits in the soft tissues of the neck that do not conform to these diagnoses. We present evidence that they represent surgical or traumatic implantation of thyroid neoplasms. Eight of the nine cases presented one to 26 years after initial surgery. Adequate information of the operative procedure was available in seven cases, one patient underwent subtotal lobectomy and six subtotal thyroidectomy for a nodular gland. The nodules occurred within the operation field with no evidence that they were within lymph nodes. In six cases, birefringent particles consistent with talc from the earlier operation were found adjacent to the nodules. Three cases showed implants of colloid nodules, three of follicular adenoma, one of oncocytic (Hürthle) cell adenoma and one of follicular carcinoma. In the ninth case, infiltrating thyroid tissue in muscle and fibrous tissue presented 3 years after major blunt trauma to the neck. The tissue resembled that in a disrupted thyroid nodule present in the gland itself and was regarded as traumatically implanted. The observation that surgery or trauma to a nodular thyroid can occasionally lead to multiple subcutaneous thyroid implants has implication for management of thyroid disease. Therapy may be difficult; recurrence followed surgical removal of the nodules in three cases, and radioiodine may be a more effective therapy. Recognition of this entity is important for accurate pathologic diagnosis. It is apparently limited to implantation of tumor. The absence of implantation of normal or hyperplastic thyroid, despite the high frequency of partial thyroidectomy in Graves' disease, has pathobiological implications. These findings also support the generally held view that lobectomy rather than nodulectomy is the operation of choice for a solitary nodule.     

Salivary gland neoplasms: diagnostic approach with focus on patterns of recognition and useful ancillary tools

Salivary gland neoplasms are rare, yet histologically diverse, posing a diagnostic challenge to many practicing pathologists. The current World Health Organization (WHO) 4th edition of head and neck tumors recognizes 31 types of unique salivary gland epithelial neoplasms, including 20 malignant and 11 benign entities. Adopting a systematic diagnostic approach with a focus on patterns of recognition is the key to accurately diagnosing these tumors. Immunohistochemistry and molecular tools can assist in making the correct diagnosis, especially when faced with overlapping morphology. In this review, we explore the utility of various immunohistochemistry and molecular diagnostic tools and outline helpful approaches in diagnosing salivary gland neoplasms.     

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.     

Histopathologic and immunohistochemical characterization of a primary papillary thyroid carcinoma in the lateral cervical lymph node

Lymph nodes in the neck are known to occasionally contain benign epithelial inclusions and can be rare primary site of various tumors usually occurring in other organs. Papillary thyroid carcinoma in the lateral neck lymph node with co-existing ectopic thyroid inclusions has not been reported previously. A 41-year-old male patient, who had normal thyroid function and no history of neck irradiation, was seen with a slowly enlarging mass in the right lateral neck. At surgery the cervical mass was found to be separate from the thyroid proper without any attachments in between. Papillary thyroid carcinoma and co-existing thyroid inclusions were identified within the lateral cervical lymph node. Immunohistochemistry detected strong and diffuse cytoplasmic positivity with antibodies against CK19 and CK903 in papillary thyroid carcinoma. Benign thyroid follicles within the lymph node were only weakly and focally stained. Thorough examination confirmed no malignancy in the total thyroidectomy specimen. Furthermore, small foci of metastatic papillary carcinoma were identified in two ipsilateral lymph nodes from neck dissection specimen. These findings suggest development of primary papillary thyroid carcinoma from malignant transformation of benign intranodal thyroid inclusions.     

Fine Needle Aspiration cytology versus Fine Needle Sampling without aspiration. A prospective study of 200 cases

In the present prospective study of 200 patients with superficial swelling of various sites, FNS followed by FNA were performed. Fifteen cases were excluded due to inadequate material. In the 80 lymph node cases, FNS was diagnostic in 85% cases as compared to FNA in 87.5%. The diagnostic accuracy was higher for FNA (87.5%) than for FNS (81.25%). However FNS smears were much superior qualitatively than FNA smears and for the diagnosis of malignant conditions FNS was found to be much better. Regarding the 68 thyroid swellings, FNS obtained a diagnosis in 82.4% cases while FNA got it in 77.9%. The diagnostic accuracy with FNS (89%) was much better compared to FNA (75%). Of the 27 breast cases FNS yielded diagnostic material in 70.38% cases while FNA was diagnostic in 85.19%, thus establishing definite superiority. However FNS seemed to be better for diagnosing malignant lesions while FNA appeared better for diagnosing benign ones. In the 5 salivary gland lesions and 5 miscellaneous lesions both FNS and FNA fared equally well. On the whole FNS technique was much more patient friendly and gave high class "text book" quality smears while FNA smears gave quantitatively more adequate material. Both the techniques therefore would be complementary to each other.     

Schwannomas: a pitfall in the diagnosis of pleomorphic adenomas on fine-needle aspiration cytology

Fine-needle aspiration cytology (FNAC) is being employed with increasing frequency for the preoperative diagnostic workup of salivary gland lesions. Although most cases show morphologic features very characteristic of specific entities, few lesions, both benign and malignant, can cause problems in interpretation. We report four cases initially diagnosed on FNA as spindle-cell tumors, possibly benign nerve sheath tumors (BNST) in the salivary gland region. These cases were later diagnosed on histologic examination as schwannoma (two cases) and as pleomorphic adenoma (two cases). Review of the cytomorphology of these four cases enabled the correct diagnosis of pleomorphic adenoma in the two cases misinterpreted as BNST. Benign peripheral nerve sheath tumors should always be considered in the differential diagnosis of pleomorphic adenoma. A diligent search for epithelial elements is recommended prior to diagnosing BNST in the head and neck region.     

Thyroid peroxidase immunohistochemistry in differential diagnosis of thyroid tumors

Thyroperoxidase (TPO) is a thyroid-specific enzyme expressed by differentiated thyroid cells. Initial immunohistochemical studies claimed that TPO expression, detected by the monoclonal antibody mAb 47, may be a potentially important diagnostic tool in differentiating malignant from benign lesions. However, some recent studies have failed to reproduce the earlier results, suggesting the limitations for TPO immunohistochemistry. To assess these observations we have evaluated the immunohistochemical expression of TPO in thyroid tissue from 215 patients. The studied material included 87 nonmalignant thyroid lesions and 128 thyroid carcinomas. TPO expression was investigated using newly available mAb 47 and staining of less than 80% of the follicular cells/specimen as the threshold indicating a malignant lesion. We found that TPO had a sensitivity of 89.9% for cancer and a specificity of 64.4% for nonmalignant lesions, showing that it does not give a sufficient degree of diagnostic certainty that the lesion is benign. In addition, the variability in the degree of TPO expression found within and between follicular carcinomas, and the significant number of benign adenomas having similar immunostaining patterns, assured us that TPO immunostaining is not sufficiently discriminatory in the differential diagnosis of thyroid cancer versus benign lesions.