Serotonin-producing pancreatic endocrine tumour. Histological, ultrastructural and immunohistochemical study of a case

Serotonin-producing pancreatic endocrine tumours are rare neoplasms which in most cases exhibit malignant biological behaviour. These tumours, in the majority of the well-documented cases, are composed of argyrophil- and argentaffin-positive cells which contain large pleomorphic neurosecretory granules. In contrast, argyrophilic non-argentaffin pancreatic endocrine tumours with tumour cells containing round neurosecretory granules are exceptional. In this study we describe such a tumour not associated with clinical evidence of carcinoid syndrome in a 60-year-old woman. Histological examination revealed tumour extension in pancreatic lymphatic vessels and veins but no evidence of locoregional or distant metastases. Ten months after surgery the patient showed no recurrence of the disease. Immunohistochemistry revealed cytoplasmic serotonin production in the tumour cells which were negative for anti-gastrin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and ACTH. This study emphasizes the usefulness of combined ultrastructural and immunohistochemical investigations in order to identify and characterize the rare pancreatic endocrine tumours with serotonin production.     

Large hepatocellular cancers: hepatic resection or liver transplantation?

Thirteen patients with primary hepatocellular cancer were studied to outline criteria for resectability in patients with large liver tumours. The mean age was 34 and the mean tumour diameter 13 cm (range 7-18 cm). Five of the tumours had a diameter of 15 cm or more. Extensive radiological investigations showed that seven of the patients had tumours of both right and left lobes of the liver, 10 had evidence of vascular invasion, and three had evidence of extrahepatic spread. Only two of the patients underwent a classically described formal hepatic resection, the rest having extensive resections crossing major anatomical planes. In no instance did the vascular invasion preclude resection, and extrahepatic spread could be verified in only one patient. The traditional criteria of resectability--that is, tumours located to one main lobe of the liver without vascular invasion and extrahepatic spread--can and should be extended. Resection may be preferable to transplantation even in patients with large primary liver tumours.     

Fine needle aspiration (FNA) cytology of pilomatrixoma: report of 14 cases and review of the literature

We describe 14 cases of pilomatrixoma which were diagnosed preoperatively on FNA cytology. In contrast to the literature, our series showed male preponderance and some of the tumours in unusual locations such as thigh and breast. In three patients the tumours were larger than 5 cm. The clinical diagnosis varied from tumour not otherwise defined to sarcoma. The cytologic presentation had features which allowed a correct diagnosis in all cases and included basaloid cells surrounded by delicate pink fibres, shadow cells, giant cells, naked nuclei and calcium deposits. It is concluded that the FNA cytology of pilomatrixoma is characteristic and will allow a conclusive diagnosis even in cases with an aberrant clinical presentation.     

Targeting the NG2/CSPG4 proteoglycan retards tumour growth and angiogenesis in preclinical models of GBM and melanoma

Aberrant expression of the progenitor marker Neuron-glia 2 (NG2/CSPG4) or melanoma proteoglycan on cancer cells and angiogenic vasculature is associated with an aggressive disease course in several malignancies including glioblastoma multiforme (GBM) and melanoma. Thus, we investigated the mechanism of NG2 mediated malignant progression and its potential as a therapeutic target in clinically relevant GBM and melanoma animal models. Xenografting NG2 overexpressing GBM cell lines resulted in increased growth rate, angiogenesis and vascular permeability compared to control, NG2 negative tumours. The effect of abrogating NG2 function was investigated after intracerebral delivery of lentivirally encoded shRNAs targeting NG2 in patient GBM xenografts as well as in established subcutaneous A375 melanoma tumours. NG2 knockdown reduced melanoma proliferation and increased apoptosis and necrosis. Targeting NG2 in two heterogeneous GBM xenografts significantly reduced tumour growth and oedema levels, angiogenesis and normalised vascular function. Vascular normalisation resulted in increased tumour invasion and decreased apoptosis and necrosis. We conclude that NG2 promotes tumour progression by multiple mechanisms and represents an amenable target for cancer molecular therapy.     

Fine needle aspiration cytodiagnosis of anaplastic carcinoma and malignant haemangioendothelioma of the thyroid in an endemic goitre area

Between 1970 and 1987, 20,028 fine needle aspirates (FNA) of the thyroid have been examined in the Department of Pathology of the University of Innsbruck, Austria. During this period 92 cases of anaplastic carcinoma and 16 cases of malignant haemangioendothelioma (MHE) of the thyroid were diagnosed. Forty-three out of these 108 highly malignant tumours of the thyroid underwent FNA pre-operatively (39.1%). Thirty-seven FNA contained numerous cells of a highly malignant tumour. Five specimens (11.8%) contained only necrotic material and inflammatory cells. In one case of an anaplastic carcinoma no malignant cells could be demonstrated in FNA. We conclude that pre-operative FNA of highly malignant thyroid tumours may contribute substantially to subsequent clinical management.     

Papillary carcinoma of the thyroid gland. Analysis of 94 cases with preoperative fine needle aspiration cytologic examination

From 1979 to 1983, 94 papillary carcinomas of the thyroid gland were examined histologically in our institute after a preoperative cytologic examination. Material for cytologic examination was obtained using fine needle aspiration (FNA) biopsy. Eighty-five (90.4%) of the 94 examined cytologic smears were representative. Among these 85 cases suspicion for malignancy or malignancy itself was found in 64 cases (75.3%). The remaining 21 smears, classified as cytologically not as suspect for malignancy, were reclassified and the previous diagnosis had to be revised in one case. In the other 20 cases no clue for malignancy could be demonstrated even after reexamination. In the 85 cases with representative cytologic findings, tumor size was determined on surgical material, in order to establish how many carcinomas with a diameter less than 3 cm could not be reached by FNA biopsy. Except for one case, all carcinomas with negative preoperative cytologic findings had a diameter less than or equal to 3 cm. The question arising is the possibility of improving the accuracy of FNA biopsy in tumor detection within cold nodules of the thyroid by combined use of scintigraphy and ultrasound-guided FNA biopsy.     

Une nouvelle observation d’une métastase testiculaire d’un adénocarcinome prostatique: Aspects diagnostiques et éthiopathogéniques

Testicular metastases from prostatic adenocarcinoma are rare. They are often asymptomatic and diagnosed incidentally or at autopsy after orchidectomy in more advanced stages of the disease. The authors report a new case and review the diagnosis and aetiopathogenesis of these metastases. A 67-year-old patient with prostatic adenocarcinoma presented with painless right testicular mass for two months with no inflammatory signs. Germ cell tumour serum markers were negative. Scrotal ultrasound showed a large testicular tumour measuring 7×4×3cm. Histological examination revealed a solid non-differentiated tumour, not suggestive of primary testicular tumour. The immunohistochemical panel confirmed the prostate as the primary site due to the positivity of cytokeratins, PSA and PSAP and the negativity of classical markers of germ cell tumours. Testicular metastases from prostatic adenocarcinoma are rare, but their incidence is currently on the increase. They are often asymptomatic and discovered after pulpectomy. This diagnosis must be considered in the case of a testicular mass in patients over the age of 50 with a history of prostatic adenocarcinoma. The diagnosis was established after orchidectomy by histological examination and immunohistochemical tests.     

A model of vascular compression in solid tumours

Often when a vascularized solid tumour reaches a diameter of 1–3 cm, central vascular compression occurs and the blood flow is confined to the peripheral outer layer. Here a model is presented which develops the concept that this vascular compression is due to the combined effect of the proliferation of cells inside the tumour and the pressure exerted on the tumour by the surrounding tissue. It is hypothesized that this occlusion eventually causes central necrosis.     

Angiosarcoma in FNA smears: diagnostic accuracy,morphology, immunocytochemistry and differential diagnoses

?. Pohar‐Marin?ek and J. Lamovec Angiosarcoma in FNA smears: diagnostic accuracy, morphology, immunocytochemistry and differential diagnoses Objective: The aim of our study was to analyse the diagnostic accuracy in recognizing angiosarcoma from fine needle aspiration (FNA) samples and to determine morphological features of angiosarcoma in cytology. Methods: FNA samples from 18 histologically confirmed angiosarcomas obtained between 1985 and 2009 were included in the study. Original cytological diagnoses were retrieved, smears reviewed and morphological features analysed: cellularity, smear pattern, cell morphology, contents of background. Outcome of immunocytochemistry was noted and additional reactions performed if material was available. Results: There were 13 primary angiosarcomas and five recurrent tumours; nine tumours were epithelioid. Twelve tumours were cytologically diagnosed as malignant, three as suspicious and three were judged unsatisfactory. Only two primary tumours were diagnosed as vascular. According to morphology, tumours were divided into those with predominantly epithelioid cells and those with predominantly spindle cells. Within these two groups were variations due to grade of tumour. Cytomorphology did not correlate well with histology in mixed and spindle cell types of angiosarcomas. Immunocytochemistry was applied in seven cases, specific vascular marker CD31 only twice at the time of diagnosis and three times retrospectively. Conclusions: Angiosarcomas are difficult to recognize on FNA smears when they lack the typical dual, spindle and epithelioid cell population and when they occur in internal organs where carcinomas are more common. Very few reliable data are available concerning specificity of CD31 on cytological material.     

Detection of medullary thyroid microcarcinoma using ultrasound‐guided fine needle aspiration cytology

G. C. H. Yang, K. Fried and P. H. Levine Detection of medullary thyroid microcarcinoma using ultrasound‐guided fine needle aspiration cytology Objective: Compared with incidental papillary thyroid microcarcinoma (microPTC), incidental medullary thyroid microcarcinoma (microMTC) is clinically more significant. The objective of the present study was to summarize our experience in detecting microMTCs. Methods: From 1995 to 2011, there were 10 825 thyroid fine needle aspirates (FNAs) guided using high‐resolution ultrasound with on‐site preparation and evaluation by a cytopathologist. Of the 140 microcarcinomas detected, 132 were microPTCs and eight were microMTCs, which are the subject of the present study. Results: All eight cases were incidentalomas and none of the five women and three men, age 37–70 years, had a family history of MTC. One patient had two FNAs at an interval of 10 months, two had a single lymph node metastasis and one had a 0.1‐cm tumour nodule near the main tumour. Four of five plasmacytoid cell microMCTs had irregular borders; two round cell and one rectangular cell tumours had smooth borders. In contrast, 17 larger MTCs diagnosed in the same period included seven plasmacytoid, four giant cell and six spindle cell types. All five plasmacytoid microMTCs were correctly diagnosed on FNA, but the round cell and rectangular cell tumours were undercalled as follicular lesions. Sampling of colloid from adjacent follicles was noted in microMTCs. Two were diagnosed on histology following recommended surgery and one was diagnosed on recommended repeat FNA. Conclusions: US‐guided FNA of thyroid lesions is a powerful tool in the detection of microMTCs, provided that cytopathologists are alerted to the pitfalls described in the present study.     

Renal FNA-based typing of renal masses remains a useful adjunctive modality: evaluation of 31 renal masses with correlative histology

Objectives:  Given the advances in renal imaging modalities in the recent years, a greater number of renal cell carcinomas (RCCs) with tumour size of <3 cm are being detected radiologically. Consequently, there is a pressing need for accurate typing of RCCs which, in turn, will aid in selection of cases of nephron-sparing surgery.
Methods:  A total of 31 cases of renal masses with available fine needle aspiration (FNA) material and concomitant histopathology details were retrieved. They included 27 RCCs (17 clear cells, eight papillary and two chromophobe), one oncocytoma, one liposarcoma and two benign lesions – one xanthogranulomatous pyelonephritis (XPN) and one benign cyst. Two investigators reviewed all FNA material. The degree of concordance between cytological typing and histological typing was assessed.
Results:  There was excellent agreement between the FNA typing and the final diagnosis, with correct classification in 28 of 31 cases. Among the three discordant cases, two were RCCs. The first was a papillary RCC (PRCC) that was misdiagnosed on FNA as clear cell RCC. Another case that was typed as a PRCC on final histopathology was diagnosed 'suspicious cells' on FNA. The third case was an XPN that was misdiagnosed on FNA as RCC with necrosis.
Conclusions:  There is an excellent concordance (90.3%) between the FNA diagnosis and the final histological diagnosis, especially in RCCs. There is a tendency for misdiagnosis with PRCC. Lesions with extensive necrosis and relatively insufficient diagnostic material on FNA specimens must be interpreted with caution. Better concordance might be observed with more extensive sampling.     

Demonstration of oestrogen receptor in symptomatic breast carcinoma, using fine needle aspiration cytology

Oestrogen receptor immunocytochemical assay (ER-ICA) was used to determine oestrogen receptor (ER) content of cells in fine needle aspirate (FNA) specimens from 88 breast carcinomas. In 49 of these the radioligand binding assay for oestradiol was available for comparison. The predictive value of ER-ICA staining for a positive radioligand binding assay (greater than 10 fmol/mg protein) was 95%. Although the predictive value of negative staining was only 66%, 34 out of 37 ER-ICA negative tumours had radioligand binding assays below 60 fmol/mg protein. ER-ICA staining showed a strong positive correlation with age of the patient, positivity being rare before the menopause. There was a weak inverse correlation with tumour grade but none with tumour size or lymph node status. The assessment of ER by immunocytochemistry using FNA cytology is a rapid technique, which may easily be repeated and provides a pre-operative assessment of ER status. It allows confirmation that tumour cells are present in the sample and an assessment of tumour heterogeneity.     

Cystic fluid and fine needle aspiration cytopathology of cystic adult granulosa cell tumor of the ovary: a case report

BACKGROUND: Fine needle aspiration (FNA) is a valuable tool in the diagnosis of ovarian cysts, especially in the young and when a nonneoplastic cyst is suspected. A case is presented with its cystic fluid, FNA and imprint cytopathology findings diagnosed as cystic adult granulosa cell tumor of the ovary (AGCT). CASE: Cystic fluid and FNA material of a 24-year-old female patient with a left-sided cystic ovarian mass 11.5 cm in diameter was sent intraoperatively for cytopathologic examination. In aspiration cytopathology of AGCT, the presence of regular tumor cells with or without nuclear grooves arranged in a follicular pattern mimicking a Call-Exner body has been regarded as the characteristic cellular feature of the tumor. CONCLUSION: For correct interpretation of the cytopathologic findings, close communication with the clinician performing the aspiration is of vital importance.     

An oestrogen-producing seminoma responsible for gynaecomastia.

In feminising testicular tumours, oestrogens can be either secreted by the tumour itself or produced by normal Leydig cells in response to paracrine and/or endocrine stimulation by hCG. Typical hormonal Leydig cell tumour patterns include: plasma oestradiol levels > 300 pmol/l on day 3 following an hCG injection, reduced plasma testosterone, and normal plasma hCG and gonadotrophin levels. Except for elevated plasma oestradiol levels, opposite results are observed in seminomas. We report a case of oestrogen-secreting seminoma mimicking a Leydig cell tumour. A 24-year-old Caucasian patient had complained of gynaecomastia for 6 months before admission. Hormonal pattern was typical of Leydig cell tumour. A 1.4 cm tumour was found in the left testis and confirmed on sonography. Considering the likely diagnosis of Leydig cell tumour, the patient was treated by tumourectomy. Surprisingly, pathological examination revealed a pure seminoma. Perifusion experiments showed that the tumour was able to secrete significant amounts of oestradiol. In addition, hCG induced a two-fold increase in oestradiol production from perifused tumour explants. Immunohistochemistry revealed that the tumour was composed of nests of seminoma cells intermingled with lymphoid infiltrates. Tumour cells also expressed aromatase, the hCG/LH receptor and the Leydig cell marker relaxin-like factor, but were betahCG-negative. These results demonstrate that a pure seminoma of the testis is able to synthesise and secrete oestrogens. They also illustrate that the body of proof favouring the diagnosis of feminising Leydig cell tumour of the testis is not rigorously specific.     

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.     

Cases with manifestation of <Emphasis Type="Italic">chemodectoma</Emphasis> diagnosed in dogs in Department of Internal Diseases with Horses,Dogs and Cats Clinic,Veterinary Medicine Faculty,University of Environmental and Life Sciences,Wroclaw, Poland

In the period of 3 years, 9 tumours of chemodectoma were supravitally diagnosed and histopathologically verified in dogs. In this period 15 351 dogs were admitted to the Clinic of Dogs and Cats and 2 145 dogs were examined in the cardiological outpatient clinic for dogs. This tumour is located in a typical place - at the base of the heart. Most frequently the tumour manifested in older boxers. Only in one case such a tumour was diagnosed in another breed of dogs. The tumours ranged in size between 3 and 16 cm in diameter. The principal sign accompanying tumours of cardiac base involved dyspnoea but in 3 cases the tumours yielded no clinical signs. All the diagnoses were additionally verified using immunohistochemical examination. We used antibodies to chromogranin A (clone DAK-A3 1:100), synaptophysin (clone SY38 1:20) and neuron-specific enolase (clone BBS/NC/VI-H14 1:150). An immunohistochemical examination is vital for the diagnosis since it allows to differentiate histologically distinct types of neoplasia which may locate in the same site and may manifest a similar histological pattern.     

Necrosis of a Hürthle cell tumor of the thyroid following fine needle aspiration. Case report and literature review

A Hürthle cell tumor of the thyroid gland resected ten days after fine needle aspiration (FNA) showed extensive necrosis accompanied by a small area of hemorrhage. Although no vascular thrombosis was noted in the histologic specimen, it is possible that the necrosis was the result of compromised vascular supply due to the FNA.     

Fine needle aspiration (FNA) of testicular germ cell tumours; a 10-year experience in a community hospital

garcía-solano j., sánchez-sánchez c., montalbán-romero s., sola-pérez j. and pérez-guillermo m. (1998) Cytopathology 9, 248–262
Fine needle aspiration (FNA) of testicular germ cell tumours; a 10-year experience in a community hospital
A retrospective reappraisal is made of the smears of 29 testicular germ cell tumours (TGCT) studied by FNA in which both orchiectomy specimens and histologic diagnoses were available. In 22 cases (75.86%) the yield was sufficient and contained cells suitable for cytologic diagnosis; in these 22 cases a diagnosis of malignancy was reached. In four cases (13.79%) the yield was sparse and diagnostic cells were partially obscured by haemorrhage and necrosis; these cases were categorized as suspicious of malignancy. In three cases (10.34%) the yield was not suitable for cytologic evaluation because haemorrhage and necrosis hampered evaluation of diagnostic cells. The cytologic findings that enable a reliable diagnosis of TGCT are described and those cytologic features that may lead the less experienced cytopathologist into an erroneous diagnosis are discussed. Pure TGCT can be confidently diagnosed with FNA and mixed TGCT can be successfully diagnosed, although it is difficult to recognize every cytologic subtype observed in the histologic sections. Despite the advantages of FNA for the prompt diagnosis of TGCT, FNA can not fully replace the histologic diagnosis and should rather be considered as a helpful tool in the work-up of testicular tumours.     

Benign mucocele-like lesion of the breast: how to differentiate from mucinous carcinoma before surgery.

The aim of the study was to improve the pre-operative diagnosis of mammary mucinous lesions. All mucinous lesions detected by fine needle aspiration (FNA) and confirmed by histological examination were reviewed by cytological findings, mammographic appearances and sonographic findings. Twenty aspirates had corresponding pathology, including 12 mucinous carcinomas, two mucocele-like lesions (MLL) with atypical ductal hyperplasia, three MLL with ductal hyperplasia and three simple MLL. Simple MLL and mucocele-like with ductal hyperplasia showed scant cellularity, no or rare intact single tumour cells, monolayered arrangement and absence of nuclear atypia. In contrast, most mucinous carcinomas showed higher cellularity, more single tumour cells, three-dimensional clusters, and mild to marked nuclear atypia. However, MLL with atypical ductal hyperplasia showed cytological features overlapping with mucinous carcinoma. MLL had a non-specific mammographic appearance and showed a cystic lesion on sonography. Mucinous carcinoma appeared as a solid mass on sonography and as a distinct nodule on mammography. Based on the combination of FNA cytology and image findings, benign MLL can be correctly distinguished from mucinous carcinoma before surgery.