化生性胸腺瘤2例临床病理分析

目的：探讨化生性胸腺瘤的临床及病理学特征。方法：应用光镜及免疫组织化学方法观察2例化生性胸腺瘤的组织学特点及免疫学表型,并复习相关文献。结果：2例均为男性,年龄55岁及56岁。组织学肿瘤显示双相分化特点,上皮细胞区域与梭形细胞区域交错分布并相互移行。上皮细胞呈相互吻合的束状、岛状及宽大的梁状排列,细胞轻度异型,可见核沟及核内假包涵体,偶见核分裂像;梭形细胞呈短束状或席纹状排列,细胞温和,未见核分裂像。免疫表型：上皮细胞区域CK19和AE1/AE3呈强阳性表达,上皮膜抗原（epithelial membrane antigen,EMA）弱阳性;梭形细胞区域表达Vimentin、Bcl-2及CD99,AE1/AE3局灶阳性,EMA弱阳性。两种区域中Ki67指数均〈5%。间质淋巴细胞CD3、CD5、CD20阳性,不表达Td T和CD99。结论：化生性胸腺瘤是一种罕见的良性或低度恶性胸腺肿瘤,诊断依靠病理组织学和免疫组织化学标记,完整切除预后良好。     

Fine-needle aspiration biopsy of ectopic cervical spindle-cell thymoma: a case report

In this report, we describe a case of ectopic cervical thymoma (medullary or type A thymoma, according to the WHO classification) located in the anterior cervical region (thyroid topography) that was submitted to ultrasound-guided fine-needle aspiration biopsy. The cytologic smears were moderately cellular to very cellular and were composed of numerous spindle-shaped cells placed predominantly in tissue fragments, with no specific arrangement. Isolated spindle-shaped cells were also present in a hemorrhagic background. The nuclei were elongated with finely granular chromatin and inconspicuous nucleoli. Mitosis, nuclear atypia, and necrosis were not detected. There was a scarce lymphoid population of small lymphocytes. The cytologic aspects, the correlation with histologic findings, and the differential cytologic diagnosis are reviewed.     

Immunohistochemical metallothionein expression in thymoma: correlation with histological types and cellular origin

Metallothioneins (MTs) are low molecular weight and cysteine-rich intracellular proteins involved in metal homeostasis and detoxication. They are found in certain normal tissues, and are overexpressed in various tumours with correlation to more aggressive behaviour in certain tumours. Since the histopathological types of thymoma have unpredictable invasive potential, MT over-expression was investigated as a possible marker of the invasive potential of thymomas. We studied immunohistochemical MT expression in 27 non-invasive thymomas, 20 micro-invasive thymomas, and 23 macro-invasive thymomas with a mouse monoclonal anti-MT antibody E9 on formalin-fixed paraffin-embedded tissues. MT expression was significantly different among the three groups of thymomas ( P  = 0.02) with a stronger expression in invasive thymomas ( P  = 0.003). However, MT expression was not exclusively limited to invasive thymomas. Therefore, it could not be used as a marker of aggressive potential in individual thymomas. Analysis of MT expression according to the histological types of the thymomas revealed that eight of nine spindle cell thymomas, none of 10 small polygonal cell thymomas, four of 14 mixed thymomas, seven of 29 large polygonal cell thymomas, and seven of eight squamoid thymomas significantly expressed MT. There was a statistically significant difference in MT expression among different histological types of thymomas ( P  = 0.000). The strongest and most consistent expression was observed in spindle cell thymoma and squamoid thymoma. Since spindle cell thymoma was usually non-invasive and squamoid thymoma was more aggressive, MT expression does not correlate with the invasive potential of different histological types of thymomas. But because medullary epithelial cells of the thymus were positive for MT, our results suggest that both spindle cell thymoma and squamoid thymoma might derive from the medullary compartment of the thymus.     

The spectrum of micronodular thymic epithelial tumours with lymphoid B-cell hyperplasia

AIMS: A rare type of thymoma, micronodular thymoma with lymphoid B-cell hyperplasia, was recently reported by Suster and Moran. Thymic epithelial tumours with a similar pattern but with varied cytological features of the tumour cells are analysed. METHODS AND RESULTS: A total of 11 cases of thymic epithelial tumours characterized by micronodular proliferation of tumour cells separated by abundant lymphoid stroma with prominent germinal centres were reviewed clinicopathologically and examined immunohistochemically. The presence of Epstein-Barr virus (EBV) genome was also examined by in-situ hybridization. Based on the morphology of tumour epithelial cells, cases were subdivided into four groups: group 1 (two cases) having spindle epithelial cells; group 2 (two cases) showing an admixture of spindle and polygonal epithelial cells; group 3 (five cases) having polygonal epithelial cells, with mild to moderate cytological atypia in four cases, and group 4 (two cases) representing lymphoepithelioma-like carcinoma. The degree of cytological atypia and the number of tumour cells positive for MIB-1 and p53 gradually increased towards group 4. The abundant lymphoid stroma in all cases contained many CD20-positive B-cells and CD3 and CD45RO-positive T-cells. CD99-positive immature T-cells were present in all cases of groups 1 and 2 and in most cases of group 3, but not in both cases of group 4 tumours. IgG, IgM and IgD-positive plasma cells and lymphocytes were also present in all cases, more prominent in those of groups 3 and 4. The EBV genome was detected in only a few lymphocytes in five cases. CONCLUSIONS: The tumours in this series belong to a distinct category of thymic epithelial tumours and each of the above groups may constitute a spectrum in the continuum of cytological atypia. The aetiological relationship of EBV with these tumours could not be proved. The lymphoid B-cell hyperplasia may result from a host immune response and may suggest a favourable clinical course of this type of tumour.     

Thymoma. A clinicopathologic study of 98 cases with special reference to three unusual cases

98 thymomas were assessed in respect to clinical manifestations, gross and histologic pathological findings and clinicopathologic correlations. 34% of patients were asymptomatic and thymoma was detected fortuitously. The most common presenting symptoms were related to myasthenia gravis, symptoms due to pressure on mediastinal structures were next in frequency. The symptom-diagnosis interval ranged from 0 to 120 months with a median of 4,5 months and was longer in invasive thymomas (median 6 months) than in noninvasive thymomas (median 2 months). 52% of thymomas were encapsulated and showed no cytologic atypia and were therefore classified as benign encapsulated thymomas. 26% showed gross invasion of peripheral structures and 3% were thymic carcinomas on histologic grounds. Histologically 55% of thymomas were epitheloid cell type, 17% spindle cell type and 20% mixed type thymomas. Epidermoid type thymoma occurred in 3% of the cases. 3 cases showed some unusual morphologic feature: one was localized intrapulmonal, another had an outspread like a mesothelioma, and the third was a basaloid carcinoma with unusual goblet cell metaplasia. In the three cases immunohistological methods were used as a diagnostic tool. The lectins UEA-I, PNA and HPA and an anti-keratin allowed the diagnosis of epithelioma (in 2 cases) and showed some more cellular and structural differentiations (in 1 case).     

Type AB thymoma accompanied by pure red cell aplasia and Good syndrome with CMV infection of tumor cells

Reported herein is a case of type AB thymoma accompanied by pure red cell aplasia (PRCA) and Good syndrome. The patient was a 55-year-old woman who was found to be anemic and to have an abnormal shadow at the left pulmonary hilus on routine medical examination. Bone marrow aspiration was performed and she was diagnosed as having PRCA. She also had hypogammaglobulinemia. The anemia was temporarily cured with oral prednisolone and cyclosporin A, and the patient underwent total thymectomy. The tumor was type AB thymoma, composed mainly of type A components; widespread spindle cell components showed slight to moderate infiltration of immature T-cells. In addition, CMV inclusion bodies were scattered throughout this tumor. The CMV-infected cells were tumor cells, because they were positive for pancytokeratin and negative for CD34. Several cases of Good syndrome with widespread CMV infection have been reported, but it is extremely rare for CMV-inclusion bodies to be found in tumor cells. No thymoma cases involving CMV infection of tumor cells have been reported.     

Fine-needle aspiration cytological findings in five cases of epithelial-myoepithelial carcinoma of salivary glands

The cytologic features of five cases of epithelial-myoepithelial carcinoma arising in major salivary glands (four parotid and one submandibular gland) are presented. All cases were initially diagnosed as low-grade malignancies. The smears were generally cellular, with no specific architectural pattern. Single cells and naked nuclei were prominent in all cases. A biphasic epithelial (small-cell) and myoepithelial (large/clear-cell) pattern was identified readily in two cases and with difficulty in one case. The biphasic pattern may be subtle or absent since the clear cells have a fragile cytoplasm and often appear as naked nuclei. The differential diagnosis includes adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and cellular pleomorphic adenoma.     

异位错构瘤性胸腺瘤1例及文献复习

目的探讨异位错构瘤性胸腺瘤(EHT)的临床及病理特征。方法复习1例EHT患者的临床病史、肿瘤组织的病理形态和免疫表型及相关文献。结果患者男性,56岁,以左胸锁关节下方皮下肿块为主要表现。肿瘤包膜完整,切面以灰白色实性为主。镜下表现复杂,以束状及平行排列的梭形细胞为主,混合有上皮成分及成熟的脂肪细胞等。瘤细胞均不具异型性,也缺乏坏死。免疫组化显示梭形细胞CK阳性,灶状细胞MSA阳性,S-100蛋白、desm in、vim entin和CD34均呈阴性。结论EHT有独特的发病部位和形态学表现,对梭形细胞上皮本质的认识是正确诊断的关键。     

Pitfalls of fine‐needle aspiration cytology of parotid membranous basal cell adenoma—A review of pitfalls in FNA cytology of salivary gland neoplasms with basaloid cell features

Membranous basal cell adenoma (MBCA) is a rare benign salivary gland neoplasm. It is difficult to diagnose MBCA based on fine‐needle aspiration (FNA) cytology due to rare reporting of its FNA cytology and overlapping of its FNA cytologic features with some benign and malignant entities. We present a case of MBCA in a 67‐year‐old female that was originally misinterpreted as adenoid cystic carcinoma (ACC) on FNA cytology. The FNA smears showed numerous uniform small basaloid epithelial cells with round or oval nuclei and inconspicuous nucleoli, and scant cytoplasm. The basaloid cells surround acellular, dense, homogenous material or are surrounded by acellular or paucicellular dense homogeneous material possibly containing bland spindle cells. The basaloid cells are present in variably sized three‐dimensional clusters, acini, or sheets with variable cohesion. The dense homogenous material surrounded by basaloid cells may be interconnected. High power magnification reveals the homogeneous material to have a fibrillar texture. The edges of dense homogenous materials were well‐demarcated. We describe the diagnostic pitfalls of FNA for MBCA, particularly versus ACC, basal cell adenoma, cellular pleomorphic adenoma, myoepithelioma, basal cell adenocarcinoma, and basaloid squamous cell carcinoma in hope of improving clinical management and patient treatment. Diagn. Cytopathol. 2015;43:432–437. © 2014 Wiley Periodicals, Inc.     

Malignant thymoma in a patient with HIV positivity: A case report with a review of the differential cytologic diagnoses

A 33-yr-old African-American male with known human immunodeficiency virus (HIV) positivity underwent CT guided fine-needle aspiration biopsy of an anterior mediastinal mass. The aspirate was composed of a dimorphic population of cells that included small mature lymphoid cells and scattered cohesive groups of large epithelial cells in equal numbers. The neoplasm stained strongly for low weight molecular cytokeratin, epithelial membrane antigen (EMA), leukocyte common antigen (LCA), and Leu-7 which was consistent with a diagnosis of thymoma. Subsequent biopsies determined the neoplasm to be a malignant (invasive) thymoma. This case emphasizes the efficacy of FNA biopsy for the evaluation of anterior mediastinal masses in HIV infected individuals. Additionally, the differential cytologic diagnoses for HIV infected individuals for this anatomic site are discussed. Diagn. Cytopathol. 16:267–269, 1997. © 1997 Wiley-Liss, Inc.     

Cytologic patterns of metastatic thymoma: Diagnosis by fine-needle aspiration biopsy

Thymomas are the most frequent primary tumors of the anterior mediastinum. These lesions are slow growing and can be locally invasive, but extrathoracic metastases are rare, occurring in less than 2% of cases. Fine-needle aspiration biopsy (FNAB) may be helpful in making the diagnosis of metastatic thymoma, with or without a clinical history of primary mediastinal thymoma. We report three cases of metastatic thymoma diagnosed by FNAB. Each case illustrates a distinctive cytologic pattern. While two of the patients had a history of histologically confirmed thymoma 11 and 13 years previously, a third patient presented with an enlarged supraclavicular lymph node and pulmonary nodules, and no prior diagnosis of thymoma. These cases demonstrate that based on distinctive cytologic patterns and features, a diagnosis of metastatic thymoma can be made with FNAB. Ancillary studies will often confirm the diagnosis. Diagn Cytopathol 1994;11:182–187. © 1994 Wiley-Liss, Inc.     

Ectopic hamartomatous thymoma: a case report with immunohistochemical and ultrastructural studies

A case of ectopic hamartomatous thymoma (EHT) arising in the supraclavicular region of a 52-year-old male is presented. The well-defined tumor measuring 1.7x1.5x0.7 cm consisted of three components: spindle cell (70%), epithelial (25%), and adipose (5%). The spindle cell component was characterized by sheet-like, haphazard and short fascicular arrangements of bland spindle cells. Neither mitotic figures nor cellular pleomorphism were found. Admixed with, and adjacent to, the spindle cell areas was an obviously epithelial component of variable appearance, ranging from glandular spaces lined by mainly cuboidal clear cells, irregularly anastomosing cords, and strands of epithelial cells to irregular solid nests of squamous epithelium with dark and clear cytoplasm. Myoepithelial cells were also observed. Immunohistochemically, the spindle cells were strongly and diffusely positive for cytokeratins and some of them were positive for BRST2, alpha-smooth muscle actin, and CD10. The tumor was negative for S-100 protein, glial fibrillary acidic protein, and CD34. Ultrastructurally, tonofilaments and desmosomes were observed in the spindle cells. The findings indicate an epithelial origin. The patient was well without recurrence or metastasis 8 months after excision. Pathologists and clinicians should be aware of the existence of ectopic hamartomatous thymoma in the supraclavicular or suprasternal region and should differentiate it from a high-grade sarcoma, such as biphasic synovial sarcoma or glandular malignant peripheral nerve sheath tumor.     

Type AB thymoma is not a mixed tumor of type A and type B thymomas,but a distinct type of thymoma

Type AB thymoma is generally regarded to be a mixture of type A and type B thymomas, but has not been studied extensively. In this study, we precisely investigated the characteristics of type AB thymoma immunohistochemically and compared it with other types of thymoma, including type A, metaplastic, and type B1 thymoma. In type A thymoma, the tumor cells were composed solely of pan-cytokeratin (CK-AE1/AE3)⁺ claudin-1⁺ vimentin^? epithelial membrane antigen (EMA)^? short spindle cells. Metaplastic thymoma exhibited biphasic architecture of epithelial islands of short spindle cells, which were phenotypically almost identical to the tumor cells in type A thymoma, and anastomosing bundles of CK-AE1/AE3^? claudin-1^? vimentin⁺ EMA⁺ fibroblast-like long spindle-shaped epithelial cells. Interestingly, we found that there were two distinctive subtypes of cell in type AB thymoma: the conventional subtype and the metaplastic subtype. The conventional subtype is characterized by type A-like components resembling type A thymoma. The metaplastic subtype is characterized by type A-like components extensively resembling the anastomosing bundles of fibroblast-like long spindle epithelial cells. Interestingly, the metaplastic subtype was a major subtype (14/19 cases), while the conventional subtype was a minor one (5/19 cases). In contrast to the rarity of metaplastic thymoma, the metaplastic subtype of type AB thymoma appears to be a major subtype of type AB thymoma.     

Cytologic diagnosis of adenoid cystic carcinoma in tracheal wash specimens

Two examples of primary adenoid cystic carcinoma of the trachea are described in which the cytologic diagnosis was made from tracheal washings. It is easy to confuse adenoid cystic carcinoma with the more common small-cell neoplasms of the respiratory tract; however, if differential features are kept in mind, such a distinction can be made in the cytologic material. Differential features include cohesive, globular, honeycomb-like arrangements of cells lacking nuclear molding, three-dimensional cell groups with ball-like formations, and clusters of uniform cells with cystic spaces, some containing mucus. These features in both of our cases resulted in unequivocal cytologic diagnoses.     

Clinicopathological features of type AB thymoma with liver metastases

Objective: We studied the clinicopathological features of type AB thymoma with liver metastases and explore the histological types, diagnosis and differential diagnosis, treatment and prognosis for this disease. Methods: Liver metastasis specimens were derived from one case of type AB thymoma 5 years after operation and were examined histologically using light microscopy and immunohistochemistry. A comprehensive analysis was performed on the patient’s clinical manifestations, histopathology, immunohistochemistry features, differential diagnosis, treatment and prognosis in combination with a review of the relevant literature. Results: Metastases were detected 5 years after initial operation on a 49-year-old, female patient with type AB thymoma. The pathological diagnosis for the liver metastases was type AB thymoma. Immunohistochemistry staining showed CKpan (+), CD3 (+), CD2 (+), TdT (+), CD5 (+), P53 (+), Hep-1 (-), and Ki67-positive cells (25%). The expression level of galectin-3 was higher than in the mediastinal thymoma tissue identified 5 years prior. Conclusion: Liver metastases of type AB thymoma are extremely rare. This case indicated that type AB thymoma with low malignant potential might recur and develop distant metastases. Overexpression of p53, galectin-3 and Ki67 in type AB thymoma might coordinately manipulate the process of development, progression and malignant transformation of type AB thymomas.     

Fine-needle aspiration biopsy of adenoid cystic carcinoma of the breast: A case report

We describe the cytologic findings of a fine-needle aspiration (FNA) breast lesion with a typical histology for adenoid cystic carcinoma. The aspirate yielded highly cellular smears with a monomorphic population of small, slightly atypical cells, arranged in multilayered groups with abundant fine intercellular metachromatic substance between cell groups. There were also fragments of fibrillar stroma in close relation to epithelial cells. The diagnosis based on the FNA material was suspicious of malignancy. The cytomorphology in this case presented a difficult differential diagnosis with pleomorphic adenoma. Features indicative of adenoid cystic carcinoma were nuclear cell hyperchromasia, the presence of small nucleoli, and scant, poorly defined, or absent cytoplasms. Differential diagnosis of breast adenoid cystic carcinoma with other entities will also be discussed. Diagn Cytopathol 1996;15:431–434. © 1996 Wiley-Liss, Inc.     

Immunohistochemical detection of bcl-2 protein in thymoma

The protooncogene bcl -2 encodes a protein that inhibits apoptosis. The protein is expressed in most epithelial cells of the fetal thymic medulla but, to the best of our knowledge, no data are available on bcl-2 expression in thymoma. Expression of bcl-2 protein was analysed in 30 cases of thymoma by immunohistological staining of paraffin-embedded tissue. All cases were examined and classified according to the Salyer and Eggleston and the Müller-Hermelink classification. In four cases, the protooncogene bcl -2 was abnormally expressed in spindle cells of pure medullary thymoma, whereas the non-spindle cells in mixed and in cortical thymoma were negative. All the lymphocytes were also strongly positive in medullary thymoma while a few lymphocytes showed light staining in other thymomas.     

Thymoma with pseudosarcomatous stroma.

Thymoma with psuedosarcomatous stroma is a recently described, rare variant of thymomas that are characterized by having a biphasic histologic pattern which consists of both an epithelial and a spindle cell stromal component. So far only 11 cases having similar histologic findings have been reported worldwide. At this time we report a case of this rare variant of thymoma which occurred in a 53-year-old Korean man. This previously healthy patient presented with coughing and an anterior mediastinal mass was then detected radiographically. Mediastinal exploration revealed a 9 x 8 x 8 cm-sized well- encapsulated, ovoid, cystic mass. Histological examination showed a biphasic neoplasm composed of anastomosing nests of epithelial cells and somewhat cellular stromal spindle cells that had advanced degenerative changes. Immunohistochemical staining using the antibodies for cytokeratins, EMA, e-cadherin, and p75NGFR showed a strong expression of these markers in the epithelial component but no expression in the spindle stromal cells. The epithelial tumor cells showed no reactivity to CD5 and L26 and a high proportion of the infiltrated lymphocytes were the cortical type that expressed CD99 and terminal deoxynucleotidyl transferase. Ultrastructural examinations revealed tonofilaments in the spindle cells. Follow up has been done for 5 years after the surgical excision and the patient has been free of disease during that period. Similar to previous reports, this patient had a benign clinical course that was unassociated with myasthenia gravis which appears to be a characteristic of this histologic variant of thymoma. However, our case also showed advanced degenerative features and we could demonstrate ultrastructural evidence of epithelial differentiation in the stromal spindle cells that were not mentioned in the previously reported cases. Based on the results of our studies, we suggest this entity is a distinct type of organotypic thymoma that shows cortical differentiation and abundant cellular stroma.     

Cytologic diagnosis of adenoid cystic carcinoma of salivary glands.

The cytomorphologic features in fine-needle aspiration (FNA) biopsies from 31 primary and 33 recurrent adenoid cystic carcinomas (ACC) were investigated. The correct FNA diagnosis was established in 24 of 31 primary ACC (77%). The diagnostic clue in aspirates from ACC are large globules of extracellular matrix, partially surrounded by basaloid tumor cells. In FNAs with predominance of basaloid tumor cells, but lacking characteristic globules, all other benign and malignant salivary gland tumors of epithelial-myoepithelial differentiation should be considered in the cytologic diagnosis. Pleomorphic adenoma is most frequently confused with ACC, and therefore, the cytologic findings in FNAs from 50 pleomorphic adenomas were compared with those diagnosed as ACC. Furthermore, rare neoplasms of salivary glands with epithelial-myoepithelial cell differentiation, including basal-cell adenoma and carcinoma, epithelial-myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma, as well as some nonsalivary gland neoplasms presenting an adenoid cystic pattern, must be considered. The cytologic features of these entities are discussed in detail with respect to the cytologic diagnostic criteria of ACC.     

Clonality analysis performed using human androgen receptor assay in a rare case of undifferentiated thymic carcinoma coexisting with type AB thymoma

We report a very rare case of combined thymic carcinomas: undifferentiated thymic carcinoma coexisting with type AB thymoma. The precise mechanism underlying the coexistence of these tumors remains unknown. Therefore, we used clonality analysis to ascertain whether the two tumors were clonally related. A 63‐year‐old woman with thyroid cancer visited our hospital. Chest computed tomography also revealed an anterior mediastinal tumor. The patient was treated with total thyroidectomy and surgery for mediastinal tumors together with left upper lobe partial resection. The mediastinal tumor was pathologically diagnosed as undifferentiated thymic carcinoma coexisting with type AB thymoma. Multiple pulmonary metastases were detected in the patient and stage IV disease was diagnosed. The tumor was treatment‐resistant, and the patient received fourth‐line chemotherapy. We conducted clonality analysis using an improved human androgen receptor gene‐amplification assay that involves random X‐chromosome inactivation through methylation, followed by methylated gene‐specific PCR amplification after sample DNA digestion with HpaII, a methylation‐sensitive restriction enzyme. Clonality analysis demonstrated identical X‐chromosome inactivation in cells present in both thymoma and thymic carcinoma areas, and thus revealed clonal proliferation. The two lesions in the patient might have arisen through the transformation of a preexisting thymoma into a more malignant lesion.