Cytology suggestive of glandular neoplasia: outcomes and suggested management

Eighty-three cases having a cervical smear result showing abnormal glandular cells were identified and matched up with the diagnostic histology result. Thirty-four (41.0%) were associated with malignancy and 26 (31.3%) with a cervical intraepithelial lesion without invasion. Thirty-eight (45.8%) had conditions of the cervix as follows: 12 cases had invasive disease of the cervix; nine (10.8%) adenocarcinoma of cervix and three (3.6%) squamous carcinoma of cervix. Nineteen (22.9%) had cervical intraepithelial neoplasia (CIN/SIL) alone and seven (8.4%) had cervical glandular intraepithelial neoplasia (CGIN) +/- CIN. There were 16 (19.3%) cases with malignancies of the uterine corpus and six (7.2%) had a malignancy arising from another primary site. Twenty-three (27.7%) had no malignant or pre-malignant condition. The risk of malignancy was related to age and ranged from 18.2% in those under 35 years to 67.9% in those 55 years and over. A protocol for the management of these cases is described.     

Role of liver scanning in the preoperative evaluation of patients with cancer

Liver scan characteristics and liver function tests of 72 patients with proved hepatic malignancy (54 metastatic, 18 primary) were evaluated. Well-defined focal defects were observed in 83% of patients with metastatic and 77% of patients with primary liver carcinoma. In 10% of the patients with metastatic liver disease the distribution of radioactivity was normal. Four or more biochemical liver function tests were normal in 33% of metastatic and 29% of primary liver cancer patients. Hepatic enlargement was present in the scan in 94% of the patients with liver metastases; however, data obtained from 104 necropsies of patients with hepatic metastases showed that only 46% had hepatomegaly. We recommend, therefore, that a liver scan should be performed before major tumour surgery in every patient with known malignancy regardless of normal liver size or normal liver function tests.     

Increased incidence of malignancy in dermatitis herpetiformis.

A retrospective study of 109 patients with dermatitis herpetiformis showed that malignant tumours had developed in seven patients, the expected incidence being 2.93, giving a relative risk of 2.38. In three of the seven patients the malignancy was a lymphoma, giving a relative risk of 100 for this tumour (expected incidence 0.03). In six of the seven patients who developed malignancies small-intestinal biopsy specimens were macroscopically abnormal, giving a relative risk of 4.22 in this group, which is similar to that reported in adult coeliac disease. Patients treated with a gluten-free diet appeared to have a reduced risk of developing malignancy compared with those taking a normal diet (relative risk with gluten-free diet 1.01 and with normal diet 3.09). A small subgroup of eight patients with linear IgA dermatitis herpetiformis were also studied: three developed malignant disease and in one the tumour was a lymphoma.     

Valeur pronostique de la TEP au F-FDG dans le bilan d’extension initial du cancer de l’œsophage traité par radiochimiothérapie exclusive

The aim of this retrospective study was to investigate the prognostic significance of initial FDG-PET in patients with newly diagnosed oesophageal carcinoma before exclusive radiochemotherapy. FDG-PET was performed in 29 patients with newly diagnosed oesophageal carcinoma before radiochemotherapy. Maximum standardized uptake value (SUV_max) was determined in each primary lesion and the presence of one or more PET-positive lymph nodes was recorded. Primary tumour volume and tumour length were assessed using two different thresholds for tumour delimitation: SUV = 2.5 and SUV = 40% of SUV_max. Patients were followed clinically during at least 1 year after initial FDG-PET. The median follow-up was 35 months (IC 95% = 26-41 months). Thirteen patients (45%) died during the follow-up. By univariate logistic regression analysis, the SUV_max of primary tumour and the presence of one or more positive lymph nodes were significantly associated with the overall survival. In contrast, no significant difference of prognosis was observed concerning age, sex, tumour cell type, primary site, clinical stage, primary tumour volume and length. Multivariate analysis was not performed due to the too small number of events. FDG-PET provides early prognostic informations in oesophageal carcinoma treated by radiochemotherapy.     

Immunohistochemical consistency between primary tumors and lymph node metastases of gastric neuroendocrine carcinoma

ABSTRACT: BACKGROUND: Gastric neuroendocrine carcinoma (G-NEC) is a rare, highly malignant tumor that exhibits aggressive growth leading to vascular invasion, distant metastasis and extremely poor prognosis. We studied the clinicopathological findings of seven patients at our institute to better under this disease. METHODS: Seven cases of G-NEC were identified among 1,027 cases of gastric carcinoma that underwent gastrectomy at Kansai Rousai Hospital between 2002 and 2010. We studied the pathological and immunohistochemical features of gastric neuroendocrine carcinomas at both the primary site and metastatic lymph nodes. RESULTS: The mean patient age was 73 years (range 63 to 86 years). There were no females in this series. The final staging was Stage I in one case, Stage II in two, Stage III in two and Stage IV in two. A total of 31 metastatic lymph nodes were found in these patients. This study revealed that the ratio of neuroendocrine cells was similar between the primary and metastatic sites, which tended to show the same expression patterns of neuroendocrine markers. CONCLUSIONS: Metastatic lymph nodes showed heterogeneous immunohistochemical expression patterns similar to the primary sites. G-NEC is far advanced at diagnosis and rapidly reaches the lymph nodes retaining its heterogeneity, carrying a worse prognosis than common gastric cancer.     

Is CSF cytology a useful diagnostic procedure in staging paediatric CNS tumours?

Objectives:  To evaluate whether there are any factors that predict malignant cells being found in paediatric cerebrospinal fluid (CSF) samples. To determine whether CSF provides useful staging information not provided by magnetic resonance imaging (MRI) in paediatric patients with primary central nervous system (CNS) malignancy.
Methods:  We compared the CSF cytology and spinal MRI staging results in paediatric patients with primary CNS malignancy at a UK tertiary referral centre, over a decade.
Results:  Of 159 CSF samples, 72 samples were from 72 patients with primary CNS malignancy with spinal MRI available for comparison. Eight of these 72 had positive cytology (seven malignant and one suspicious). All had a high clinical suspicion of tumour at the time of sampling. Of the 72 patients, only two had evidence of CSF spread on MRI spinal staging and CSF cytology; ten had MRI without cytological evidence and six had cytological without MRI evidence.
Conclusions:  In paediatric patients with primary CNS tumours, CSF cytology provides useful staging information. Spinal MRI alone may miss some patients with CSF spread who would be identified with CSF cytology.     

Posters. P19 Cervical carcinoma with metastases to the tympanic membrane: an unusual presentation

Introduction Fine needle aspiration (FNA) is a well‐established diagnostic technique which is frequently used to diagnose head and neck neoplasms. Clinical decisions concerning treatment of malignant salivary gland tumours, the extent of surgery and advisability of pre‐operative irradiation can be helped by prior knowledge of tumour type. Aim The aim of this study was to do an audit of all salivary gland FNAs carried out in Beaumont Hospital over a 14‐year period. Methods All salivary gland FNAs between 1989 and 2002 were reviewed. Where available, the corresponding follow‐up histological specimens were studied. Results During this 14‐year period, 305 patients with salivary gland lesions had FNA of the lesion performed. The total number of aspirates performed was 343. Of these, 184 had histologies available for follow‐up. Eighty‐nine aspirates were reported as inadequate; 89 as inflammatory, normal or consistent with cyst contents. One hundred and thirteen aspirates were diagnosed as a benign entity. Thirty‐three aspirates were reported as malignant (21 of which were felt to be primary to the salivary gland and 12 metastatic). Sixteen cases were called suspicious. Good correlation between FNA findings and histology was seen in the majority of cases (145 of 183). Some diagnostic problem areas were identified. These included the following: lymphomas (seven called benign on FNA), Warthin's tumour (seven not diagnosed or misdiagnosed on FNA) and mucoepidermoid carcinoma (one reported as pleomorhic adenoma and one as benign/cystic on FNA). Seven pleomorphic adenomas were not diagnosed on FNA pre‐operatively, predominantly due to inadequacy of the specimen. Three other malignancies (acinic cell carcinoma, lymphoepithelial carcinoma and carcinoma ex‐pleomorphic adenoma), while not diagnosed on FNA, were called suspicious, with re‐biopsy advised. Conclusion FNA cytology of salivary glands is an accurate method for evaluation of both benign and malignant lesions, enabling optimum surgical and adjuvant therapy decision‐making pre‐operatively. Well‐defined problem areas are identified and, therefore, clinicopathological correlation is required in these cases.     

Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Comparison with the diagnostic accuracy on small histologic biopsies

The accuracy of identification of tumor type and primary site of malignant tumors by examination of exfoliated tumor cells was cytologically studied in 448 malignant effusions from 366 patients for whom the primary tumor site had been confirmed by histology. Ninety-seven corresponding small biopsies from metastases were separately reviewed histopathologically. In four fluids, the cells were too scanty or too poorly preserved for tumor typing. The cytologic tumor typing was performed with nearly 100% accuracy in the remaining 444 fluids, except for those of intermediate-cell anaplastic carcinomas (0 of 3) and poorly differentiated squamous (epidermoid) carcinomas (1 of 5). Adenocarcinoma was correctly identified in 98% of 285 fluids, large-cell carcinoma in 97% of 108 fluids, oat-cell carcinoma in 94% of 16 fluids, well-differentiated (keratinizing) squamous carcinoma in 100% of 3 fluids, malignant lymphoma in 100% of 22 fluids and sarcoma in 100% of 2 fluids. The criteria and the failures are discussed at length. In the investigation of the accuracy of cytologic and histologic diagnoses with respect to the primary tumor site, tumors with variable sites of origin (sarcomas and lymphomas) and those with usually singular sites of origin (e.g., small-cell anaplastic carcinoma of the lung) were excluded, leaving 387 cytologic and 83 histologic specimens available for review. The breast as a primary site was correctly identified in 70% of both the cytologic and histologic specimens; the primary cytodiagnostic criteria included a uniform cell pattern, finely granular chromatin, dense cytoplasm and cell balls with smooth borders. Ovarian primaries were correctly identified in 70% of the fluids and 83% of the biopsy samples on the basis of very irregular clusters of large pleomorphic tumor cells, large nucleoli and psammoma bodies. Lung primaries, identified in 50% of the fluids and 29% of the biopsy samples, showed quite variable cell patterns, most often including large pleomorphic cells with or without mucus formation and prominent multinucleation. Gastric cancers of the diffuse type were accurately identified in 52% of the corresponding fluids, which showed mainly isolated cells with dense cytoplasmic rims, occasional signet-ring cells, "embryo-shaped" nuclei, marked hyperchromasia and densely granular chromatin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Polyarthritis associated with gastric carcinoma.

In a 68-year-old man who had polyarthritis associated with gastric carcinoma surgical resection of the tumour was accompanied by prompt resolution of the arthritic syndrome. In 11 years of follow-up the arthritis has remained in complete remission and there has been no recurrence of the carcinoma. An awareness that polyarthritis may be a presenting manifestation of an underlying carcinoma may, especially in an elderly person, lead to early recognition and treatment of the malignant disease.     

Scintigraphy with [111In]octreotide and 201Tl in a Hürthle cell thyroid carcinoma without detectable radio-iodine uptake. Report of a case and review of the literature

AIM: To describe the visualization of recurrent disease by [111In]octreotide and 201Tl scintigraphy in a patient with Hürthle cell thyroid carcinoma, increased thyroglobulin levels, and a negative radio-iodine total-body scan. METHODS: Scintigraphy with [111In]octreotide and 201Tl was performed, and a local recurrence in the thyroid bed was detected which was excised by surgery. RESULTS: On histology, the tumour proved to be a Hürthle cell carcinoma, and within the tumour somatostatin receptors were detected by RT-PCR. CONCLUSION: Scintigraphy with [111In]octreotide and 201Tl is an alternative imaging method for the detection of residual disease in patients with a differentiated thyroid carcinoma having increased thyroglobulin levels and a negative radio-iodine total-body scan.     

Behaviour modification: three techniques for decreasing the stress of hospitalization and surgery.

Scintiscanning to detect the uptake of bone-seeking radioactive isotopes by soft tissue is a promising technique for the in vivo study of visceral calcification. Visceral uptake of such radioisotopes was studied in 40 patients: 22 undergoing long-term dialysis, 9 with malignant disease and hypercalcemia and 9 with primary hyperparathyroidism and hypercalcemia.Fifteen patients, 11 undergoing dialysis and 4 with malignant disease, had radioisotope uptake in the lungs, and 5, 3 undergoing dialysis and 2 with malignant disease, had uptake in the stomach. None of the patients with primary hyperparathyroidism had visceral uptake, nor did the patients with uptake have radiologic evidence of pulmonary or gastric calcification. The dialysis patients with visceral uptake had a mean calcium × phosphate product of 84.3 ± 23.7 (standard deviation), which was significantly greater (P < 0.001) than that of patients without such uptake (59.2 ± 14.0). Similarly, in patients with malignant disease and visceral uptake the Ca × P product was 72.2 ± 6.4 — significantly greater (P < 0.005) than that of patients without such uptake (49.3 ± 6.7).These findings indicate that scintiscanning for the visceral uptake of a bone-seeking radioisotope is a simple and effective technique for the in vivo study of visceral calcification. An elevation in the Ca × P product seems to be the single most important factor in the production of visceral calcification.     

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.     

Bronchiolar Carcinoma: A Report of Six Cases

Bronchiolar carcinoma is a malignant tumour which apparently arises in a terminal bronchiole from which it spreads either by bronchial embolization or by lymphogenous and/or hematogenous dissemination. It is not a common neoplasm.Histologically, the tumour bears a striking resemblance to the disease of sheep, jagziekte, which is of virus etiology. A very common finding in reported cases is preexisting pulmonary fibrosis. At the Nova Scotia Sanatorium, Kentville, 80 cases of primary lung cancer have been encountered within the past 25 years. Six of these were bronchiolar carcinomas. Five patients had co-existing chronic pulmonary disease, bronchiectasis in one and tuberculosis in four. One patient died of a rapidly progressive bilateral lesion and five were explored. Lobectomy was done in all five, but in one for palliation only. Three patients are alive and well three, six and 14 years, respectively, after their operations.     

Recent Canadian court decisions on consent.

A 51-year-old woman presented with a painful, rapidly enlarging thyroid gland. The serum concentrations of the thyroid hormones were initially at the upper limit of normal, and the uptake of radioactive iodine by the thyroid was completely depressed. Although subacute thyroiditis was suspected, a biopsy specimen from the thyroid showed malignant disease and no evidence of inflammation. At the time of right subtotal lobectomy metastatic breast carcinoma was diagnosed. Thus, primary or secondary malignant disease of the thyroid can simulate thyroiditis and present a serious problem in differential diagnosis.     

Problems in assessing multiple cutaneous melanoma. A review on the accuracy of a population based cancer registry

Databases with information on malignant tumors are of great value for epidemiologic studies. From the Regional South Swedish Tumour Registry, which is of documented high quality, 24 patients out of 8008 with reported melanoma diagnosis 1973–2003 were reported as having multiple (≥3) primary, invasive cutaneous malignant melanomas (CMM). Of the 76 tumours identified in these patients, 7 (9%) were found not to be invasive melanomas. Additional cases could be put into question since the lesions could be interpreted as epidermotropic metastases, a diagnosis which can be difficult to establish reliably by microscopic examination. Among the 24 patients we could also identify 8 (10%) additional lesions representing invasive CMM, not included in the Tumour Registry database. Thorough information concerning an earlier melanoma diagnosis and its site of presentation is needed from the clinician and the pathologist for optimal assessment of the histology and the prognostication of the patient, as well as proper reporting to a tumour registry. Identifying multiple primary malignant melanomas is also of special importance for counselling patients belonging to families with hereditary disease. In this study it is shown that diagnosing and reporting multiple malignant melanomas can be problematic due to insufficient communication and to the rare and deceptive capability of cutaneous metastases to imitate primary tumours.     

Sex steroid binding patterns in primary biliary cirrhosis complicated by hepatocellular carcinoma.

Owing to recent findings of certain unusual sex steroid binding in liver disease--particularly an allosteric biphasic pattern (pattern A) unique to the serum of patients with hepatocellular carcinoma--the serum binding characteristics for 5 alpha-dihydrotestosterone were examined in serum samples from six patients with primary biliary cirrhosis who had developed hepatocellular carcinoma. In all serum samples taken after the development of tumour pattern A binding only was obtained, and in four cases in which earlier samples were also examined there was a transformation from the normal, non-specific binding pattern, or an allosteric plateau pattern seen in non-malignant liver disease (designated D and C respectively), to pattern A coincident with the rise in serum alpha fetoprotein. In one patient chemotherapy leading to a fall in alpha fetoprotein abolished pattern A binding, showing further its close association with tumour growth. The value of pattern A binding as a tumour marker in hepatocellular carcinoma warrants further study.     

Hypermétabolismes médullaires en TEP au 18F-FDG chez les patients atteints de cancer : signification et comparaison à l’IRM médullaire

Diffuse bone marrow uptake of ¹⁸F-FDG-PET in cancer patients raises the problem of differential diagnosis between marrow involvement and stimulated marrow. In this study, we prospectively included, during a 1-year period, all cancer patients referred for initial staging showing an unexplained diffuse bone marrow uptake and explored consecutively by MRI. The abnormalities described on PET and the conclusion reached about disease status of bone marrow (“benign” or “malignant”) were compared with corresponding MRI results, as well as clinical and biological findings pertinent when bone marrow activity is studied, marrow status considered by referring clinicians, and follow-up data. During 1 year, 60 patients had diffuse bone marrow uptake on ¹⁸F-FDG-PET, 26 underwent MRI examination and were finally included in the study. Results of PET and MRI were concordant in 24 cases (six “malignant” and 18 “benign”) and two cases were discordant, judged “malignant” by MRI and “benign”by PET. The outcome after confrontation of MRI and PET, was “malignant”for one patient and “benign” for the other one. The final results, was “malignant” for seven patients and “benign” for 19 patients and this final diagnosis was retained by referring clinicians. Among the 19 patients with diffuse bone marrow uptake considered as benign, seven patients had a pejorative evolution and four of them developed osteomedullary metastases. In cancer patients, ¹⁸F-FDG-PET identify bone marrow diffuse uptake which seems to correspond well to abnormalities assessed on MRI studies. Notably, heterogenous 18F-FDG uptake and/or foci of increased uptake seems significative of marrow involvement. The limited population size and discordant published findings about bone marrow evaluation by ¹⁸F-FDG-PET compared with MRI can not permit to ensure that these imaging modalities or one of these are sufficient to assess bone marrow status without performing bone marrow biopsy. Some patients with unexplained diffuse bone marrow uptake develop disease progression, such observations could be interestingly assessed by further studies.     

Thyroid Scanning with 131Cs

Scanning of the thyroid gland after the administration of radioactive caesium (¹³¹Cs) was performed in 45 patients; in 38 of these it had been shown that a thyroid nodule failed to accumulate sodium per-technetate (^99mTc) or sodum iodide (¹³¹I). ¹³¹Cs was concentrated in the nodule to a greater degree than in the paranodular thyroid tissue in seven patients, in five of whom thyroid carcinoma was subsequently identified. In five patients ¹³¹Cs accumulated in both the nodule and paranodular tissue, while in the other 26 no ¹³¹Cs uptake occurred in the nodule. In only one of the latter group was the thyroid lesion malignant. Caesium scanning seems to offer a useful supplementary procedure in the investigation of thyroid nodules.     

The role of PET-CT in detecting unknown primary tumour in patients with cervical lymph node metastases

PET-CT examination was conducted with 440 patients treated at the Department of Head and Neck Surgery, National Institute of Oncology, Budapest, between January 1, 2006 and December 31, 2010. Out of them 77 patients were selected with whom no examination of any sort (physical, pan-endoscopy, or any of the conventional imaging techniques) succeeded in identifying the primary tumour. In each case the primary examination (aspiration cytology and histology) verified cervical metastases, most of them being squamous cell carcinoma. The significance of PET-CT was retrospectively evaluated in cases of unknown primary tumour with verified cervical metastases. We tested the sensitivity of PET-CT in detection of the primary malignant tumour, and possible distant metastases or a second primary in order to plan an optimal treatment schedule for the patient. Patients with whom the examinations specified in the treatment protocol (physical examination, pan-endoscopy, conventional imaging, biopsy) had failed to diagnose the primary tumour were referred to PET-CT. In each case 18F-FDG tracer was used. In 21/77 patients (27%), the PET-CT yielded unequivocal evidence for the primary tumour confirmed by histology, as well. With 10 others (13%), the precarious diagnoses by various imaging techniques were confirmed by the PET-CT. False positive findings with PET-CT that were not verified either by histology or control examination tests occurred but in 10 patients (13%). Concerning the primary tumour, false negative result was obtained only with 3 patients (4%). It should be noted that their retrospective evaluation proved diagnostic errors, the primary tumours were visible in all the scans. With 33 patients (43%) PET-CT furnished no additional information compared to the previous examinations. In 10 patients, asymptomatic distant metastases and in 3 patients synchronous tumours were diagnosed. We also acknowledge that the significance of PET-CT using 18F-FDG is unquestionable in the detection of unknown primary tumours. It is strongly recommended to re-include the detection of unknown primaries in the approved national indication list of PET-CT. (Note, until January 1, 2008 it had been included!) PET-CT is capable of detecting a primary tumour, after all unsuccessful diagnostic examinations till then, in 25-40% of the cases. One cannot disregard the role and significance of PET-CT in the detection of asymptomatic synchronous tumours, or distant metastases. These benefits make PET-CT a suitable tool for the refinement of individually tailored treatment strategies leading to better therapeutic results and more favourable cost-benefit ratio.