Cytopathologic features of pituitary carcinoma with cervical vertebral bone metastasis: a case report

BACKGROUND: Pituitary carcinomas are extremely rare tumors of the adenohypophysis. The presence of craniospinal and/or systemic extracranial metastases is the only reliable criterion for the diagnosis of pituitary carcinoma. To date, only 2 cases have been reported correctly by fine needle aspiration biopsy (FNAB). We present an additional case of pituitary carcinoma with FNAB features. CASE: A 60-year-old woman presented with clinical features of Cushing's disease and a pituitary tumor. She underwent transsphenoidal resection of the tumor. The initial diagnosis was an adrenocorticotrophic hormone (ACTH)-producing invasive pituitary adenoma. The patient presented again with neck pain 6 years after the operation. Magnetic resonance imaging revealed metastatic tumor masses at the level of C5-C6 of the cervical vertebrae. Intraoperative fine needle aspiration and incomplete excision of metastatic tumors were performed. Cytologically, tumor cells were composed of a combination of loose groups and single cells. Neoplastic cells had a relatively monotonous appearance and displayed characteristic neuroendocrine tumor features. Immunocytochemistry from cell block sections revealed AE1/ AE3, synaptophysin chromogranin A and ACTH positivity in the tumor cells. CONCLUSION: Pituitary carcinoma with extracranial systemic metastases demonstrates typical neuroendocrine features on fine needle aspiration. In the differential diagnosis, metastatic neuroendocrine carcinomas should be kept in mind. In the absence of sufficient clinical data, these 2 entities cannot be distinguished correctly through the cytologic features.     

鞍区常见肿瘤影像学诊断现状

鞍区占位包括垂体起源的和非垂体起源的占位性病变,其中以垂体腺瘤最为常见。由于鞍区其他占位性病变在颅内的解剖位置与垂体腺瘤十分接近,因此垂体腺瘤的诊断与鞍区其它肿瘤的鉴别诊断,是影像科医师所面临的挑战。将鞍区其它少见的占位性病变与垂体腺瘤相鉴别,给出正确的诊断对于指导临床手术入路和避免术中和术后出现并发症(如脑脊液漏、颅内感染),具有重要意义。其中鞍区占位性病变常需要将垂体腺瘤与Rathke囊肿、颅咽管瘤、鞍区脑膜瘤、脊索瘤、颅内转移瘤相鉴别。本文总结了目前垂体腺瘤等其他占位性病变的影像学表现以及影像学特征,以便于鞍区常见肿瘤的诊断和鉴别诊断。     

Phenotypical and Pharmacological Characterization of Stem-Like Cells in Human Pituitary Adenomas

The presence and functional role of tumor stem cells in benign tumors, and in human pituitary adenomas in particular, is a debated issue that still lacks a definitive formal demonstration. Fifty-six surgical specimens of human pituitary adenomas were processed to establish tumor stem-like cultures by selection and expansion in stem cell-permissive medium or isolating CD133-expressing cells. Phenotypic and functional characterization of these cells was performed (1) ex vivo, by immunohistochemistry analysis on paraffin-embedded tissues; (2) in vitro, attesting marker expression, proliferation, self-renewal, differentiation, and drug sensitivity; and (3) in vivo, using a zebrafish model. Within pituitary adenomas, we identified rare cell populations expressing stem cell markers but not pituitary hormones; we isolated and expanded in vitro these cells, obtaining fibroblast-free, stem-like cultures from 38 pituitary adenoma samples. These cells grow as spheroids, express stem cell markers (Oct4, Sox2, CD133, and nestin), show sustained in vitro proliferation as compared to primary cultures of differentiated pituitary adenoma cells, and are able to differentiate in hormone-expressing pituitary cells. Besides, pituisphere cells, apparently not tumorigenic in mice, engrafted in zebrafish embryos, inducing pro-angiogenic and invasive responses. Finally, pituitary adenoma stem-like cells express regulatory pituitary receptors (D2R, SSTR2, and SSTR5), whose activation by a dopamine/somatostatin chimeric agonist exerts antiproliferative effects. In conclusion, we provide evidence that human pituitary adenomas contain a subpopulation fulfilling biological and phenotypical signatures of tumor stem cells that may represent novel therapeutic targets for therapy-resistant tumors.     

Use of monoclonal antibodies to glial fibrillary acidic protein in the cytologic diagnosis of brain tumors

Monoclonal antibodies were used to immunocytochemically demonstrate glial fibrillary acidic protein (GFAP) in 174 smear preparations of brain tumor tissue in order to investigate the presence and distribution of GFAP in a variety of intracranial tumors and to evaluate the value of this technique in the cytodiagnosis of brain tumors. GFAP-positive cells were found in the astrocytic tumors and in some of the oligodendrogliomas, ependymomas and medulloblastomas. In contrast, schwannomas, meningiomas, a primary lymphoma, a hemangiopericytoma pituitary adenomas, germinomas and metastatic tumors were negative for GFAP. The cytodiagnostic accuracy of the 174 brain tumors was raised from 90.8% to 97.1% when GFAP-immunoperoxidase staining was employed to aid the routine cytologic diagnosis. These findings indicate that immunoperoxidase staining for GFAP can be successfully applied to cytologic specimens and is a useful adjunct to routine cytologic diagnosis.     

Decisive role of intermediate filament typing of tumor cells in the differential diagnosis of difficult fine needle aspirates

Thirty-six diagnostically difficult fine needle aspirates from enlarged lymph nodes and malignant soft tissue tumors, containing tumor cells with scanty or no obvious light microscopic features indicative of their differentiation, were assessed by a panel of six cytopathologists. Their diagnoses were recorded and then compared with the definitive diagnosis established by combining the cytologic findings with the results of intermediate filament typing of tumor cells in the smears using monoclonal antibodies specific for each filament type. The results show that use of these antibodies can markedly improve the accuracy of the cytologic diagnosis of tumor type as well as revise or prevent erroneous cytologic diagnoses in difficult cases. This pertains especially to the differential diagnoses of carcinoma versus malignant lymphoma, carcinoma versus malignant melanoma, carcinoma versus sarcoma and squamous carcinoma versus carcinoma of simple epithelia. Intermediate filament typing of tumor cells in aspirates as an objective histogenetic criterium makes the differential diagnosis of the difficult aspirates much more reliable and reproducible, provided that appropriate questions are asked, monoclonal antibodies with well-defined specificities are used and the antigenicity of the intermediate filaments in smears is preserved.     

Application of artificial neural network for classification of thyroid follicular tumors

OBJECTIVE: To analyze smears of 197 thyroid follicular tumors (adenoma and carcinoma). STUDY DESIGN: Several types of artificial neural networks (ANN) of various designs were used for diagnosis of thyroid follicular tumors. The typical complex of cytologic features, some nuclear morphometric parameters (area, perimeter, shape factor) and density features of chromatin texture (mean value and SD of gray levels) were defined for each tumor. RESULTS: The ANN was trained by means of cytologic features characteristic for a thyroid follicular adenoma and a follicular carcinoma. At subsequent testing, the correct cytologic diagnosis was established in 93% (25 of 27) of cases. The morphometry increased the accuracy of diagnosis for follicular tumors in up to 97% (75 of 78) of cases. ANN correctly distinguished an adenoma or a carcinoma in 87% (73 of 84) of cases when using color microscopic images of tumors. CONCLUSION: The usage of ANN has raised sensitivity of cytologic diagnosis of follicular tumors to 90%, compared with a usual cytologic method (sensitivity of 56%). The automatic classification of thyroid follicular tumors by means of ANN is prospective.     

miR-134在人垂体腺瘤组织中的表达及其意义(英文)

目的:探讨垂体腺瘤患者miR-134的表达及意义,分析其表达水平与无功能垂体腺瘤(non-functioningpituitaryadenomas,NFPA)增殖侵袭能力的相关性。方法:选择2010年6月至2013年7月本院收集垂体腺瘤标本104例以及8例尸检正常腺垂体的临床资料。采用实时荧光定量PCR、免疫组织化学技术检测Ki-67、MEG3、miR-134等在NFPA组织中的表达水平,并分析数据。结果:miR-134在NFPA组织中表达水平显著低于正常腺垂体和其他类型垂体腺瘤(P0.01);miR-134的表达水平与NFPA患者肿瘤侵袭性、肿瘤细胞Ki-67阳性率及发病年龄呈负相关(P0.01)。结论:miR-134表达下调可能是NFPA肿瘤发生及肿瘤呈侵袭样生长的重要因素,miR-134可作为诊断和评估NFPA预后的参考指标。     

Comparative cytomorphology of pituitary adenomas and oligodendrogliomas in intraoperative crush preparations.

Minute fresh tissue fragments from 20 pituitary adenomas and 18 oligodendrogliomas were crushed between two glass slides and stained with hematoxylin and eosin for cytologic examination. These two tumor types displayed distinctive cytologic features that may permit their correct identification. Pituitary adenomas were characterized by single and clustered tumor cells with monomorphic, round or vesicular nuclei that were commonly denuded of cytoplasm. Rare well-preserved tumor cells showed well- or ill-defined, variable and granular cytoplasm. Oligodendrogliomas showed cells with monomorphic or slightly pleomorphic nuclei and scant, fibrillary, wispy cytoplasm, commonly arranged in clusters or around circular and empty spaces.     

Characterization of human pituitary adenomas in cell cultures by light and electron microscopic morphology and immunolabeling

The morphology and hormone production of pituitary adenoma cell cultures were compared in order to highlight their characteristic in vitro features. Cell suspensions were prepared from 494 surgical specimens. The 319 viable monolayer cultures were analyzed in detail by light microscopy and immunocytochemistry within two weeks of cultivation. Some cultures were further characterized by scanning, transmission and immunogold electron microscopy. The viability and detailed in vitro morphology of adenoma cells were found to be characteristic for the various types of pituitary tumors. The sparsely granulated growth hormone, the corticotroph and the acidophil stem cell adenomas provided the highest ratio of viable cultures. Occasionally, prolonged maintenance of cells resulted in long-term cultures. Furthermore, a variety of particular distributions of different hormone-containing granules were found in several cases. Both light microscopic and ultrastructural analyses proved that the primary cultures of adenoma cells retain their physiological features during in vitro cultivations. Our in vitro findings correlated with the routine histopathological examination. These results prove that monolayer cultures of pituitary adenoma cells can contribute to the correct diagnosis and are valid model systems for various oncological and neuroendocrinological studies.     

Proliferating cell nuclear antigen (PCNA) expression in pituitary adenomas: relationship to the endocrine phenotype of adenoma

The expression of proliferating cell nuclear antigen (PCNA) correlates to cell proliferation and for this reason it is commonly considered as one of proliferation markers. Since proliferation rate is an important factor determining the tumor aggressiveness, the evaluation of PCNA index (the percentage of PCNA-immunopositive nuclei in the investigated tumor sample) is suggested as useful in predicting pituitary adenoma outcome. Seventy three unselected, surgically removed pituitary adenomas were immunostained with antibodies against the pituitary hormones or their subunits and against the proliferating cell nuclear antigen (PCNA). The highest PCNA index was found in ACTH-immunopositive tumors without the manifestation of the Cushing's disease ("silent" corticotropinomas). This value was significantly different in comparison to other adenoma subtypes including corticotropinomas manifesting themselves by Cushing's disease. The lowest PCNA index was noticed in monohormonal GH-secreting tumors. The adenomas which express more than one hormone (plurihormonal adenomas) seem to have a higher PCNA indices than monohormonal ones; the difference was significant in the case of mono- and plurihormonal prolactinomas. The recurrent tumors presented a higher mean PCNA index as compared to the primary tumors, although the difference was significant only in the case of prolactinomas. These findings suggest that the proliferative potential of pituitary adenomas is related to the tumor recurrence and hormone expression.     

Hyaline-cell pleomorphic adenoma. Diagnosis by fine needle aspiration biopsy

The cytologic, histologic, immunohistochemical and ultrastructural characteristics are presented of a case of hyaline-cell pleomorphic adenoma of the soft palate diagnosed by aspiration biopsy. Hyaline cells are commonly found in pleomorphic adenomas of minor salivary gland origin. The lack of cohesiveness of the hyaline cells makes them readily amenable to sampling by fine needle aspiration biopsy. When identified in a neoplasm, these cells are characteristic, and probably diagnostic, of a mixed tumor.     

Fine needle aspiration biopsy of Hashimoto's thyroiditis. Sources of diagnostic error.

OBJECTIVE: To determine the accuracy of cytologic interpretation in the diagnosis of Hashimoto's thyroiditis (HT). STUDY DESIGN: At Ottawa Hospital from 1987 to 1994, 1,638 fine needle aspiration biopsies (FNABs) from thyroid were performed. HT was suggested in 184 FNAB samples taken from 157 patients. Of the 184 aspirates diagnosed with HT, 39 had corresponding surgical specimens taken from 31 patients. A retrospective review of these FNABs and surgical pathology slides formed the basis of this study. RESULTS: In 27 (69%) aspirates, HT was diagnosed on both the FNAB and surgical specimens. In 10 of 27 FNABs an associated lesion was not sampled by FNAB. In four of these 10 aspirates some of the cellular features of HT were misinterpreted, and the possibility of an associated neoplasm could not be ruled out. This resulted in four false positive diagnoses. In 12 (31%) FNABs from nine patients, the cytologic diagnosis of HT was not confirmed histologically. These cases included five Hürthle cell adenomas and one case each of follicular adenoma, nodular goiter, macrofollicular adenoma and malignant lymphoma. This resulted in five false negative diagnoses. CONCLUSION: These results support the value of FNAB in the diagnosis of HT. The presence of hyperplastic follicular cells on FNAB samples from HT may mimic a follicular neoplasm and result in a false positive interpretation. Adequate sampling of the thyroid is important, particularly when there is an associated lesion. The diagnosis of lymphocytic thyroiditis should not be made when only a few lymphocytes are present. Finally, pleomorphic Hürthle cells may be present in aspirates from Hürthle cell neoplasms and underdiagnosed as HT, especially when they are associated with a few lymphocytes.     

Cytology of a chromophobe pituitary adenoma. A case report

A pituitary tumor with suprasellar and extrasellar extension was investigated by means of the squash-smear cytologic technique. The dominant cell type was large, round to oval cells, with pale-staining, finely granular cytoplasm. The nuclei of these cells often contained single or multiple inclusions of uncertain nature. There also were cells with eosinophilic cytoplasm, usually collected in small nests. Hyperchromatic "naked" nuclei, in various shapes, were immersed in a homogeneous, faintly staining ground substance. Mitotic figures were detected easily. Cytology of these combined cell types allowed the intraoperative diagnosis of a rather pleomorphic pituitary adenoma.     

Metanephric adenoma vs. Wilms' tumor: a report of 2 cases with diagnosis by fine needle aspiration and cytologic comparisons

BACKGROUND: Metanephric adenoma (MA) is a rare benign renal neoplasm that can occur at any age, whereas, Wilms' tumor (WT) is the most common malignant renal neoplasm in children and is occasionally seen in adults. CASES: In case 1, a 26-year-old male had a left renal mass. Fine needle aspiration (FNA) showed 3-dimensional sheets of cells with nuclear overlapping, molding, irregular nuclear membrane and distinct nucleoli. Frequent mitotic figures could be seen. The cytologic differential diagnosis included Wilms' tumor, neuroectodermal tumor and metanephric adenoma. Nephrectomy revealed Wilms' tumor. In case 2, a 24-year-old female presented with erythrocytosis and a right renal mass. FNA showed small, uniform cells with smooth nuclear membrane, fine chromatin and inconspicuous nucleoli. A diagnosis of metanephric adenoma was made and confirmed on nephrectomy. CONCLUSION: Differentiating MA from WT based on cytologic features on FNA biopsy prior to surgical resection can he difficult.     

Molecular aspects of pituitary tumors

Pituitary adenomas are common benign neoplasms, accounting for approximately 15% of intracranial tumors. In systematic autopsy, pituitary tumors are found in 25%, of the population, but only one-third of these tumors give rise to clinical manifestations. Why most of these neoplasms remain undiagnosed and pituitary carcinomas are extremely rare? The progress in the studies concerning pituitary tumorigenesis is rather slow and, due to several limitations, including the anatomic inaccessibility of human pituitary gland, the lack of functional human cell lines in culture and the discrepancies between human and animal pituitary oncogenesis (in rodents pituitary hyperplasia is a prerequisite for adenoma development). In humans, the majority of pituitary tumors are monoclonal in origin and derived from single mutated pituicyte, rarely hyperplasia is a prerequisite for adenoma formation. As in the case of other tumors, activating mutations in oncogenes (GNAS1, PTTG) and inactivating mutations in tumor suppressor genes (MEN1, CNC1) lead to pituitary tumors development. However, mutations in classic oncogenes are very rarely associated with these tumors. Moreover, the important role of some hypothalamic hormones, peripheral hormones and their receptors (e.g. GHRH, dopamine D2 receptor, PRL receptor, estrogens, thyroid hormone receptor) and growth factors (e.g. FGF, EGF, TGF) is postulated and partially proved in promotion of pituitary tumorigenesis. Further studies are required to determine which of these events are truly primary changes in pituitary tumorigenesis, what may allow development of gene therapy.     

Cytologic features of central neurocytomas of the brain. A report of three cases

BACKGROUND: Although cytologic smears are major tools for intraoperative diagnosis of intracranial tumors, cytologic features of central neurocytoma, a tumor that has been recognized for only about 15 years, have not been described. CASES: Typical central neurocytomas were encountered in three patients: 40 years old/M, 44/M and 31/F. Intraoperative cytologic smears were reviewed, and all tumors were subsequently examined by conventional histology, immunohistology and, in one case, electron microscopy. The important cytologic appearances were sheets of round cells with finely stippled nuclear chromatin and perinuclear haloes. Calcospherites, neuropil islands and rosettelike structures were focally encountered. The background neuropil was finely fibrillated, but the tumor cells possessed no appreciable cellular processes. CONCLUSION: Central neurocytomas possess distinct cytologic features that help with the intraoperative distinction from oligodendrogliomas and other intraventricular tumors. A combined radiologic and morphologic approach to the diagnosis of this tumor is advised.     

MiR-26a在人垂体腺瘤组织及血清中表达的研究

目的：miRNA遍及生命体的发生、发育、分化和死亡的过程。它在肿瘤、心血管、糖尿病等多种疾病的各个阶段中起到调控癌基因作用。miRNA在垂体腺瘤中异常表达,且影响垂体腺瘤的增殖、侵袭及凋亡情况。本研究通过探讨miRNA家族中的miR-26a在垂体腺瘤组织及血清中的表达变化情况,为垂体瘤的早期诊断及疗效监测提供依据,以便更好的指导临床诊断及治疗工作。方法：收集哈尔滨医科大学附属第四医院微创神经外科手术切除并经病理证实的垂体腺瘤20例,取其组织及采集血清标本：年龄在20-74岁（平均50岁）,术前均未进行任何治疗。既往无内分泌疾病的正常死亡人的垂体组织及其血清标本20例作为对照组。采用实时定量聚合酶链式反应（Real-timePCR）方法分别检测垂体腺瘤病人和正常人组织及血清中的miRNA-26a的表达情况。用SPSSl3．0统计分析软件运用Mann—WhitneyU检验方法对数据进行统计学分析。结果：miRNA-26a在垂体腺瘤组织中的表达量为22．30,正常垂体组织中的表达量为23．38,垂体腺瘤患者血清中miRNA-26a的表达表达量为25．04,正常对照组血清中的表达量为24．95,垂体腺瘤组织中的表达较正常垂体组织中的表达明显升高（P〈0．05）,垂体腺瘤患者血清与正常人血清中miRNA-26a的表达无明显差异（P〉0．05）。结论：垂体腺瘤组织中miRNA-26a的高表达与血清学检测miRNA-26a的正常表达,为预防脑垂体腺瘤的发生和发展提供了重要的临床诊断依据。     

Mucinous tubular and spindle cell carcinoma of the kidney: Report of a case with imprint cytologic features

BACKGROUND: Mucinous tubular and spindle cell carcinoma of the kidney is a newly established subtype in the World Health Organization classification. The tumor has a good prognosis, and its diagnosis is clinically important. However, there are no reports of its cytologic features. Here we report the cytologic findings of this rare tumor. CASE: A 68-year-old female had left-sided abdominal pain, fatigue and hematuria. A large mass in the left kidney was removed. Histologically, the tumor was compatible with mucinous tubular and spindle cell carcinoma. Imprint cytologic examination revealed a large amount of tumor cells arranged in tubular, sheetlike and spindle structures. Some tumor cells showed clear cytoplasm. Nuclear atypia was mild, with occasional distinctive nucleoli. CONCLUSION: The cytologic features of mucinous tubular and spindle cell carcinoma have a varied appearance. It should be included in the differential diagnosis to avoid overtreatment.     

Neuronal differentiation and expression of neural epitopes in pituitary adenomas.

Neural transdifferentiation is increasingly recognized in neural crest and neural stem cell tumors. Neuronal differentiation has been anecdotally described primarily in somatotroph cell adenomas associated with acromegaly, but its prevalence in adenomas and relationship to adenoma type has not been completely established. In this study we performed a retrospective morphological and immunohistochemical analysis of neurofilament, phosphoneurofilament, Neu-N, class III tubulin, and Hu in WHO grade I pituitary adenomas. Limited numbers of cells with neuronal features and neuron-associated epitopes may be more common in pituitary adenomas than previously recognized. These may occur in many forms of adenomas including somatotroph, lactotroph, mixed somatotroph and lactotroph, null cell/gonadotroph cell and, rarely, corticotroph cell adenomas.     

Leiomyosarcoma of the breast: report of a case with fine needle aspiration cytologic, histologic and immunohistochemical features

BACKGROUND: Leiomyosarcoma of the breast is a rare neoplasm. We present a case of primary leiomyosarcoma of the breast in a middle-aged female in whom fine needle aspiration cytologic features suggested sarcoma. CASE: A 55-year-old female presented with a rapidly growing breast lump of 1 month's duration. On examination, an ulcerating, 12 x 10 cm tumor was seen involving the lower medial and lateral quadrants of the right breast. Fine needle aspiration cytology showed variably sized, dissociated and loosely clustered polygonal, plump and spindle cells with pale blue cytoplasm and vesicular nuclei that were round, oval or irregular. Occasional giant forms and nucleolated and mitotic cells were present. A single cluster of benign ductal cells was seen. The tumor cells did not express immunocytologic reactivity to estrogen receptor protein. A cytologic diagnosis of sarcoma was given with differential diagnoses of metaplastic carcinoma and malignant phyllodes tumor. Histologic study established the diagnosis of leiomyosarcoma. Leiomyosarcoma of the breast shows fine needle aspiration cytologic features of sarcoma, but specific tumor typing may not be possible, especially when the cytologic material is inadequate for ancillary staining required to distinguish leiomyosarcoma from metaplastic carcinoma and malignant phyllodes tumor.