Aspiration cytology, immunocytochemistry and electron microscopy of a malignant peripheral neuroectodermal tumor. A case report

The findings of fine needle aspiration (FNA) cytology, immunocytochemical staining and electron microscopy (EM) in a case of malignant peripheral neuroectodermal tumor (PNET) presenting as a soft tissue mass in the lateral abdominal wall are reported. The immediate evaluation of the aspirate revealed cells of a small round cell malignant tumor. To provide a specific preoperative diagnosis, additional cytologic material was aspirated for immunocytochemical and ultrastructural investigations. While the results of EM were nonspecific, allowing only the exclusion of other small round cell malignancies, immunocytochemical staining of the aspirate was suggestive of a PNET. The diagnosis of PNET was corroborated by histopathologic and immunohistochemical findings. This case indicates that an exact preoperative categorization of small round cell malignant tumors can be made by FNA biopsy in otherwise equivocal cases when immunocytochemical and ultrastructural techniques are also utilized.     

Peripheral neuroectodermal tumour (neuroepithelioma) of the thoracopulmonary region: light and electron microscopic cytology

We describe a case of peripheral neuroectodermal tumour of the thoracopulmonary region diagnosed by fine needle aspiration cytology. Light microscope examination revealed numerous small tumour cells arranged in large irregular aggregates occasionally delimiting empty vascular-type spaces or forming rosette-like structures. Cytologically the tumour cells showed a marked degree of nuclear anaplasia, scanty cytoplasm and long thin cytoplasmic processes. Electron microscopy revealed cells with characteristics of neuroectodermal differentiation.     

Primitive neuroectodermal tumor of the uterus. A case report

BACKGROUND: Primitive neuroectodermal tumor (PNET) is a rare tumor derived from fetal neuroectodermal cells. These tumors occur in the central nervous system and in peripheral locations. Histologic diagnosis is the standard since most of these tumors are detected at an advanced stage. CASE: A 17-year-old female presented with persistent vaginal bleeding. Physical examination revealed a 4-cm, hard, barrel-shaped cervix. A cervicovaginal smear was obtained. The specimen was hypercellular, with small to medium-sized, round, malignant cells. A diagnosis of PNET was made from the histologic sections of the surgical specimen. CONCLUSION: When numerous small round cells in a diffuse pattern are seen on a Pap smear, the differential diagnosis is long and difficult. However, with careful evaluation of the cytologic features, a few reasonable differential diagnoses can be reached. Furthermore, with liquid-based Pap smears, material is available for immunohistochemical staining to narrow the range even more. Using all resources, including a good clinical history, a cytopathologist can give the clinician an early diagnosis for intervention and treatment.     

Fine needle aspiration cytology of primitive neuroectodermal tumors. A report of these cases.

Primitive neuroectodermal tumor (PNET) is a small round cell malignancy arising in soft tissue and bone, predominantly in older children and adolescents. We report the cytomorphologic features and findings of ancillary studies of eight fine needle aspiration (FNA) biopsies from three patients (7-year-old male, 12-year-old female, 9-year-old female). Two of the biopsies suggested the initial diagnosis of PNET of the chest wall, while the remaining six documented recurrent or metastatic disease. In one of these cases the primary diagnosis made by FNA biopsy enabled the pediatric oncologists to give specific therapy for the unresectable tumor and achieve remission. Local recurrences included the chest wall (two cases), pleura (one case) and pericardium (one case), while metastatic disease involved the supraclavicular lymph node and breast. All the cases consisted of small malignant cells with a high nuclear/cytoplasmic ratio and hyperchromatic nuclei without prominent nucleoli. Homer Wright rosettes were seen in only two of the aspirates, and neuropil and ganglion cells were not present. Ancillary studies, including electron microscopy (two cases), immunocytochemistry (four aspirates from two cases) and cytogenetics (11/22 translocation, one case) performed on the aspirated material were aids in making a specific diagnosis and excluded other small round cell tumors of childhood, such as malignant lymphoma, rhabdomyosarcoma and Ewing's sarcoma. The differential diagnosis between PNET and neuroblastoma can be difficult on the basis of an FNA biopsy alone, although light microscopic morphologic differences exist. Clinical features (e.g., age, primary site, metastatic patterns), catecholamine levels, electron microscopy and cytogenetics are necessary in establishing the correct diagnosis.     

Retroperitoneal primitive neuroectodermal tumour (PNET). A case report and review of the literature

PurposeWe report a clinical case and present a brief review of the literature of peripheral primitive neuroectodermal tumour (PNET) as a rare disease. We discuss the difficult clinical and pathological diagnosis and the multidisciplinary approach to treatment of PNET. We debate radiosensitivity of extracranial recurrent retroperitoneal PNET.Methods and materialsExternal beam radiation therapy was applied for a non-resectable local recurrence of retroperitoneal PNET in a 74-year-old woman. There were no distant metastases and our patient has refused chemotherapy.ResultsLocal tumour control (LTC) was achieved after administration of a total dose of 60 Gy in 30 fractions by external beam 60 Cobalt radiotherapy.ConclusionsPNET is an aggressive malignant tumour infiltrating lymphatics and metastasizing haematogenously. It requires a multimodality treatment. Late local recurrence of extracranial retroperitoneal PNET has shown high radiosensitivity, so local tumour irradiation could be a radical treatment even in non-resectable cases.     

Diagnosis of Metastatic Pleomorphic Giant Cell Carcinoma of the Pancreas Using Fine Catheter Aspiration Cytology

The value of fine catheter aspiration cytology in the diagnosis of metastatic tumours is illustrated by a case of pleomorphic giant cell carcinoma of the pancreas which had metastasized to the peritoneal cavity. The finding of unequivocal malignant cells obviated the need for further diagnostic procedures. Electron microscopy and immunostaining further substantiated the light microscopic cytodiagnosis and identified the tumour type and source of the primary tumour. Furthermore, subsequent cell block preparation from the aspirated material demonstrated the histological features of this tumour.     

肩关节原始神经外胚层肿瘤1例

原始神经外胚层肿瘤分为中枢性和外周性两类,是起源于原始神经管胚基细胞的未分化的高度恶性的肿瘤。外周性原始神经外胚层肿瘤源于神经嵴,可发生在骨、软组织,生长在盆腔、腹腔、腹膜后、肺及胸壁的肿瘤也有报道。发生于骨关节的PNET以青壮年多见,女性多于男性,病程1年以内,以局部疼痛伴软组织肿块为特点,软组织肿块内囊变或钙化少见;可发生于长骨及扁骨,其中肱骨好发。骨骼以溶骨性为主要表现,少见肿瘤骨。病理以镜下可见H-W菊形团结构,免疫组化染色Vim、CD99强阳性为特点。本例为女性患者,影像学特点以右肩关节周围软组织肿块及肩胛骨溶骨性破坏为主。肿块内未见肿瘤骨及明显骨膜反应。CT扫描肿瘤的分界欠清,对邻近组织侵袭性不强。MRI扫描可见肿瘤等信号为主,T2WI肿瘤内部可见片状高信号影。由于PNET恶性程度高,当肿瘤发生于骨内,需要与尤文氏肉瘤(EW)鉴别。     

Comparative analysis of electron microscopy and immunocytochemistry in the cytologic diagnosis of malignant small round cell tumors

OBJECTIVE: To compare the contributions of electron microscopy (EM) and immunocytochemistry (ICC) as adjuncts in the cytodiagnosis of malignant small round cell tumors (MSRCT). STUDY DESIGN: This prospective study included 57 cases with a preliminary aspiration diagnosis of MSRCT. The contributions of EM and ICC in arriving at a specific diagnosis were evaluated. RESULTS: The 57 cases included 22 cases of Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), 12 neuroblastomas, 8 Wilms' tumors, 6 rhabdomyosarcomas, 5 lymphomas, 2 retinoblastomas and 1 synovial sarcoma. One case remained unclassified. Electron microscopy was crucial to the diagnosis in 38.4% cases as against 39.2% of cases by ICC. The light microscopic diagnosis was confirmed in 42.3% and 53.5% cases by EM and ICC, respectively. EM and ICC were inconclusive for a specific diagnosis in 19.2% and 7.1% of cases, respectively. Technically unsatisfactory preparations in EM and ICC accounted for 5 and 1 cases, respectively. The overall efficiency in making a diagnosis was 80.7% for EM versus 92.8% for ICC. Aberrant expression of antigens led to difficulties in interpretation of ICC, and EM was particularly helpful. The ultrastructural demonstration of neural differentiation in Ewing's sarcoma/PNET tumors helped place tumors in the PNET category. CONCLUSION: While ICC is the ancillary method of choice in the cytologic diagnosis of MSRCT, EM contributes to the diagnosis and improves diagnostic accuracy.     

O-9AUDIT ON BK VIRUS DETECTION IN RENAL TRANSPLANT RECIPIENTS

Introduction and Aims:  The sensitivity of bronchial cytology (brushings, washings) is in the region of 70–80%. Therefore a significant number of false negatives occur. The main aims of this study were to: (i) To identify negative bronchial washings and brushings performed in 2004 with malignant follow-up and (ii) To ascertain the cause of the false negative result where possible. 56 patients with negative bronchial cytology and subsequent malignant follow-up on a pulmonary specimen were identified. These cases formed the basis of the study.
Results:  In our series peripheral tumour location and specimen inadequacy accounted for the majority of false negative results. Malignant cells were missed in a minority of cases (5 of 56). An explanation for failure of diagnosis in 4 of the 5 cases was paucity of malignant cells. In one case of small cell carcinoma, malignant cells were abundant, but were not recognized.
Recommendations:  What can be done to reduce the false negative rate?
(1) In cases where radiology has indicated that the tumour is peripherally located patients could proceed directly to fine needle aspiration.
(2) Improved communication between clinicians and pathologists is required in relation to: (a) specimen adequacy and (b) degree of clinical suspicion.     

Stereotactic biopsy and cytological diagnosis of solid and cystic intracranial lesions

Cytological smears from 115 consecutive cases of stereotactic biopsies of intracranial lesions were reviewed. Ninety-five lesions were solid and 20 cystic. Material from 90 solid and 13 cystic lesions was sent both for cytological and histological examination. In 66 of the solid lesions, the cytological diagnosis was confirmed by histology (five were benign lesions and 61 malignant tumours: 56 primary brain tumours, three metastases and two lymphomas). In 24 cases with discrepant cytology and histology, the histology was inconclusive or insufficient in 14 cases, while cytology established the diagnosis of astrocytoma grade II (seven cases), metastases (two cases), gliosis (one case) and benign (four cases). Necrosis of tumour type was observed cytologically in six patients representing glioblastoma (two cases), anaplastic astrocytoma (one case), lymphoma (one case) and normal brain (two cases) histologically. Three cases reported cytologically as benign were primary brain tumour (two cases) and gliosis (one case). One smear of a glioblastoma was insufficient for cytological diagnosis. Cystic lesions were cytologically benign in 17 cases and malignant in three cases. Histology from the cyst wall confirmed the malignant diagnosis in three cases and showed tumour in six more cases, a benign process (two cases), changes induced by radiotherapy for arteriovenous malformation (one case) and insufficient material (one case). In conclusion, cytology from solid brain lesion allows an accurate diagnosis and subtyping of tumours in a majority of cases, and can thus be used to choose type of therapy. In cystic brain tumours, however, examination of the cystic fluid, is often inconclusive and a biopsy from the cyst wall should be performed if there is clinical or radiological suspicion of tumour.     

Primitive Neuroectodermal Tumour (PNET) in subcutaneous abdominal wall: a case report

Primitive neuroectodermal tumour (PNET) is a rare tumour mainly found in children under ten years old. It may be broadly categorised into those occurring from the central or peripheral nervous system of which the majority arise centrally. We report a 61 year-old lady who had previous lobular breast cancer presenting with a rapidly expanding lesion in her anterior right upper abdominal wall. Clinically it appeared to be benign, however, histopathology of the excised lesion revealed a localised PNET. This case is an unusual case of a PNET in an adult that is peripheral in nature arising from subcutaneous tissue in the abdominal wall.     

Primary cervical lymphoma: the role of cervical cytology

Two cases of primary malignant lymphoma of the uterine cervix are reported. Both were confirmed by histology as high grade B cell lymphomas. In one case, the diagnosis was made on a second colposcopic biopsy after an initial cervical smear and colposcopic biopsy were negative. In the second case, dyskaryotic cells of uncertain type were identified in a cervical smear taken at colposcopy performed as part of follow up for previous cervical intraepithelial neoplasia (CIN)I. The cytologic features and differential diagnosis of this rare cervical neoplasm are discussed, with emphasis on the role of the Papanicolaou smear in the initial diagnosis of this tumour.     

Surgical treatment of neuroendocrine tumours of the pancreas

Gastro-entero-pancreatic (GEP) endocrine tumours can originate from various pancreatic islet cells, from endocrine cells of the gastric and duodenal mucosa, or from APUD cells of neuroectodermal origin in the gastrointestinal tract. They are benign when smaller than 2 cm, but larger tumours are generally malignant. Surgery is the only method for the curative treatment of GEP tumours. A diagnosed and localised tumour is an absolute indication for radical surgery. Conservative medical treatment may be indicated only in an inoperable condition, but in this case tumour reduction surgery is suggested. In the last 15 years 22 patients with pancreatic neuroendocrine tumours were treated without any mortality. Except for two of them, the surgical therapy was curative.     

Cytotoxic peripheral T cell lymphoma arising in a patient with nodular lymphocyte predominant Hodgkin lymphoma: a case report

In this paper, we describe a case of nodular lymphocyte predominant Hodgkin lymphoma with the subsequent development of a peripheral T cell lymphoma. This case is unusual in that the sheets of atypical and small to intermediate-sized T cells in the diffuse component were CD8 positive and expressed cytotoxic proteins. The diagnosis of peripheral T cell lymphoma was supported by the demonstration of a clonal T cell receptor beta chain gene rearrangement by Southern blot analysis. Peripheral T cell lymphoma with a cytotoxic phenotype is a rare entity with an aggressive clinical behavior. As such, this report emphasizes the need to consider a diagnosis of coexisting peripheral T cell lymphoma in cases of nodular lymphocyte predominant Hodgkin lymphoma with atypical features, such as few or poorly defined B cell macronodules and diffuse T cell areas. The examination of both T cell receptor gamma and beta chain gene rearrangements should be performed to confirm such cases.     

Mesothelioma Symposium 11.30–12.30 Tuesday 16 September 2003. Cytopathology of malignant mesothelioma

The diagnosis of malignant mesothelioma on the cytology of serous effusions is a two‐phase process. First is to determine that the effusion is malignant based on morphological features such as a highly cellular fluid with many large three dimensional cell aggregates, and/or the recognition of minor malignant criteria including prominent cell engulfment, uniformly present very prominent nucleoli, or the finding of very large (giant) cells. In cell block sections, strong positive staining with EMA often with cell membrane accentuation provides compelling support for a cytological diagnosis of malignancy. Second is to recognize that the malignant cells have a mesothelial phenotype and do not represent metastatic malignancy (usually adenocarcinoma). Criteria in support of mesothelioma include the lack of a ‘two cell’ population, that is one native (mesothelial) and one foreign (metastatic), cells with abundant dense staining cytoplasm, the presence of ‘windows’ where mesothelioma cells lie in close apposition and intracytoplasmic glycogen presenting either as small peripheral vacuoles on MGG stained smears or large yellow refractile crescents on Papanicolaou stained smears. In addition, mesothliomas often possess connective tissue stromal cores occurring as either well‐formed collagen within papillary aggregates or lying free as pink (MGG) or light green (Pap) amorphous material in the background of the smear or in loose association with mesothelioma cells. Finally small orange staining squamous‐like cells can occasionally be identified and sometimes this may be a very prominent finding and has resulted in the false impression of a squamous cell carcinoma. Almost certainly these cells represent apoptotic tumour cells. The connective tissue mucin hyaluronic acid may be found as a net‐like pattern in the smear background or as large hard‐edged magenta‐stained vacuoles on MGG‐stained smears. Cell block sections provide architectural information and it is usually possible to separate mesothelioma aggregates with their cuboidal cells, central nuclei and abundant dense cytoplasm arranged in solid, papillary or hollow clusters from those of adenocarcinoma with less dense, often foamy cytoplasm, often composed of columnar cells with elongated nuclei. Aggregate form in adenocarcinoma can be variable but true acini are a rare finding. These cell block sections provide an ideal medium for histochemistry (PAS with and without diastase digestion) and immunocytochemistry. By using a panel of antibodies (Calretinin and CK 5/6, BerEp4, CEA, B72.3) it is almost always possible to distinguish mesothelioma from metastatic adenocarcinoma. Calretinin and CK 5/6 positive staining and absent staining with BerEp4, CEA and B72.3 is considered diagnostic of mesothelioma.     

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.     

Differential activation of cytotoxic responses by Burkitt's lymphoma (BL)-cell lines: relationship to the BL-cell surface phenotype

Epstein-Barr (EB) virus-positive Burkitt's lymphoma (BL) cell lines, recently established from tumour biopsies and displaying chromosomal translocations indicative of their malignant origin, can be classified into two broad sets: (i) lines growing predominantly as single cells/small clumps whose cell surface markers remain close to those of the original tumour cells, and (ii) lines whose growth pattern and cell surface markers have progressed closer to the more "lymphoblastoid" phenotype displayed by all in vitro transformed B-cell lines (LCLs) of normal origin. When compared to LCLs derived from normal B cells of the same patient, BL-cell lines in set (i) generally showed a lower expression of HLA class I and class II antigens and a reduced ability to activate both allospecific and nonspecific (natural killer-like) cytotoxic responses when cocultured with peripheral blood lymphocytes. By contrast, the HLA antigen expression and in vitro stimulatory capacity of most BL-cell lines in set (ii) were much closer to the values displayed by their corresponding LCLs. Since set (i) rather than set (ii) BL cell lines are phenotypically representative of the malignant cells as they exist in vivo, this work suggests that successful outgrowth of the virus-carrying tumour cells in the affected host may be facilitated by the inability of these cells to stimulate strong cytotoxic responses.     

Analysis of surface membrane antigens, cytoskeletal proteins and N-myc oncogene in pediatric solid malignant tumors, their diagnostic usefulness and relevant problems]

Neuroblastoma (NB), primitive neuroectodermal tumor (PNET), Ewing's sarcoma and rhabdomyosarcoma (RMS) are solid malignant tumors in childhood. Microscopically these tumors are grouped as small-round-cell tumors, and a different diagnosis is sometimes difficult. Cell surface membrane antigen, cytoskeletal protein and N-myc amplification and over-expression were analyzed in these cell lines and tumor tissues for the accurate diagnosis. NB and PNET could be distinguished from Ewing's sarcoma and RMS by the panel of monoclonal antibodies against cell surface membrane antigens. The cytoskeletal protein analysis is useful for the diagnosis of RMS and leiomyosarcoma. Alpha-smooth muscle actin and/or desmin were demonstrated in the S-type (epithelial-like) cells in 3 NB cell lines, suggesting the differentiation pathway of NB into smooth muscle cells. N-myc amplification and over-expression were observed in NB cell lines as well as one RMS cell line. The occurrence of N-myc amplification and over-expression in the RMS cell line cautions us against using N-myc as a distinguishable marker for NB.