Virtual Journal Club (VJC) - Cytopathology
Volume 3, Number 1, April 2007

Full acknowledgement goes to Dr G Leiman of Vermont, who prepared this useful summary.

Acta Cytologica, Volume 50, Number 4, July-August 2006

1. FNA of Vertebral and Paravertebral Lesions (124 cases), page 364.
   Vertebral and paravertebral fine needle aspirations are usually done as a matter of urgency, and are the most likely events to get Cytopathologists up at night. Literature on their efficacy is scant. Authors from Jackson, Mississippi have collated the findings in 124 cases of both bony vertebral and soft tissue paravertebral lesions. There is an accompanying editorial by Syed Z. Ali of Johns Hopkins. The article is worth reading for a full listing of benign and malignant tumors encountered, as well as inflammatory and other benign lesions. FNA of this area has a high diagnostic accuracy and specificity, to the extent that supportive or adjunctive biopsies and other tests were often of no increased diagnostic value in this study.
2. Pheochromocytoma and Retroperitoneal Paraganglioma, page 372.
   This article, from Madrid & Guadalajara, reviews 15 samples/ 12 patients/ 13 tumors. The procedures were performed without prior suspicion of the diagnosis, and thus without special precautions. One patient in the series developed a hypertensive crisis requiring immediate intravenous anti-hypertensive treatment. Morphology is highly variable, ranging from small round bare nuclei through to highly pleomorphic cells. I do not recall seeing a case in the last 7 years in this Department, and bring it to your attention for conscious consideration of the entity in appropriate cases.

Diagnostic Cytopathology, Volume 34, Number 7, July 2006

1. EUS-FNA of IPMN, page 457.
   This experience from Indiana confirms that IPMN has a high prediction for subsequent development of adenocarcinoma. As in other series from other centers, EUS-FNA is not used as extensively in IPMNs, nor is it as accurate, as it could be. Cytology consists of abundant mucinous background, hypocellularity on occasion, and papillary groups of mucinous epithelium with goblet cells. Despite widespread publication of cytologic details, many cases are missed, and are found only on post-surgical review to have contained diagnostic material. This leads to anly “moderate” rather than high sensitivity of EUS- FNA, with a minority of cases being correctly identified. Being “conscious” of this entity could improve diagnostic accuracy. This small center in Indiana has had 62 surgical cases of IPMN over the last nine years; other institutions similarly report a recent “epidemic”. We should not be missing this lesion, with its high transformation rate to mucinous or other adenocarcinoma.
2. Cytologic-Histologic Correlation of Pap Tests, page 503.
   If you want to see the worst abstract in the world, look at this article!
3. Staining of Trichomonas with p16, pages 512.
   In a previous issue, Liron Pantanowitz reported that Trichomonads could stain with p16 and could mimic small parabasal-sized cells from a high grade SIL. Two investigators from Germany and Italy have now shown that this is indeed the case, but only with the antibody clone G175-405 produced by Pharmingen. When they tested Trichomonas with p16 made by Dako or by CINtec, no such staining was observed. This aberrant staining is therefore a peculiarity of antibody clone G175-405.
4. FNA and Flow is Rapid and Accurate in Palpable Lymphoid Lesions, page 472.
   If you need yet another article to show the disbelievers and the deniers that FNA and flow cytometry can adequately and accurately diagnose lymphoid lesions, this is an excellent article from Curie Institute in Paris. Sadly, these articles appear mainly in the cytopathologic literature, where they are easily overlooked by clinicians and particularly by oncologists.

Diagnostic Cytopathology, Volume 34, Number 8, August 2006

1. Adjunctive Testing for Malignant Mesothelioma, page 523.
   The authors conclude, in a series of 14 patients with mesothelioma, 12 with carcinomas and 13 with reactive effusions, that there is NO usefulness in adjunctive testing by immunocytochemistry or by electron microscopy. This starkly contradicts most previous publications and is all more ridiculous as the authors have not used either calretinin or TTF-1. One has to wonder about the standard of peer review in a case such as this.
2. . Detection of Tumor Cells in Fluids by Flow Cytometry, page 528.
   This is a possibility that has long been of interest to me, but this is the first article on the subject I have seen. In essence, the addition of ploidy analysis to cytomorphology and immunocytochemistry added nothing to the accuracy of diagnosis of malignancy in body fluids. One of the chief reasons for this is the mimicry of malignancy by reactive mesothelial cells when viewed by the laser flow cytometry.
3. Warthin’s Tumor with Multiple Granulomas, page 564.
   In a study of six cases of Warthin’s tumor with granulomas, which comprised 1.6% of 382 cases (!)of Warthin’s tumor in a Chinese medical center, the authors showed that the presence of granulomas in Warthin’s tumor pre-dates fine needle aspiration, as evidence of granulomas was found in the FNA of two cases. This should put to rest prior claims that the granulomas of Warthin’s are linked to prior FNA.
4. FNA of Thyroid Insular Carcinoma, page 572.
   This interesting and well-illustrated article from Yolanda Oertel, a doyenne of thyroid cytopathology, describes a case of insular carcinoma in FNA, emphasizing rosette formations (not follicular aggregates), nuclear pleomorphism and, yet again, occasional intranuclear cytoplasmic inclusions. These cases are sent to keep cytopathologist on their toes. In essence, the cytopathology resembles the follicular variant of papillary carcinoma, until one notices that the detached aggregates are rosettes rather than follicles.

Cancer Cytopathology, Volume 108, Number 3, June 2006

1. PapSpin: A Reasonable Alternative to Other Liquid-Based Tests, page 137.
   This is the latest article in a growing literature on the search for alternative, cheaper technology to create thin layers by cytospin, and to enable HPV studies, utilizing equipment which may be found in any cytopathology lab. This “PapSpin”, has previously been called the “ThinSpin”. I would appreciate those with more technical expertise reading this article in which Dorothy Rosenthal et al from Johns Hopkins optimized the method, and compared it with conventional smears in a split sample study of 482 women. Results were almost identical in both slide groups. The article states that the preparation time is similar to that of the T2000 instrument, and although not approved by the FDA, would be cheaper based on a kit available in Europe. Certainly the fields chosen for photography indicate lesions very clearly and illustrate a comfort level with the interpretation of the preparatory technique described in the article.
2. ThinPrep and Cytospin in Exfoliative NON-GYN Cytology, page 144.
   On the very next page, Tariq Elsheikh from Muncie, Indiana, shows great superiority of the ThinPrep over CytoSpin for non-gynecologic exfoliative samples!
3. IPMN of Pancreas; Cytology Predicts Histologic Grade, page 163.
   While others are floundering with the diagnosis of IPMN in FNA (see above), Martha Pitman et al of Massachusetts General Hospital have perfected not only the recognition, but also the prediction of grade of these tumors in fine needle aspirations. The illustrations in this article, in color, are very informative. By the way, the authors also claim that the presence of epithelial cells is not necessary for the diagnosis of IPMN when thick “colloid-like” mucin is present in abundance, in the appropriate clinical setting! Further, GI contamination is emphasized as a known diagnostic pitfall. The authors describe small tight clusters and single “dysplastic cells” as being indicative of low grade lesions, with sheet-like parachromatin clearing seen in high grade IPMNs.
4. FNA of the Liver: CT Versus EUS, page 180.
   The indefatigable David Chhieng from the University of Alabama found the results of percutaneous CT- guided FNA to be identical to those of endoscopic ultrasound FNA, the one limitation to the latter obviously being that the lesion should be in the left lobe of the liver within easy reach of the duodenum. Once again, GI cells are mentioned as a pitfall in diagnosis.
5. Mucin Profile in FNA Pancreas, page 186.
   As if in answer to the problem of GI sheets, the equally indefatigable Prabodh K Gupta and colleagues from U Penn report on immunocytochemistry for various mucin subtypes in cell blocks made from pancreatic FNAs. In essence, MUC-1 was found in non-neoplastic pancreatic ductal and acinar cells. MUC- 2 was found only in goblet cells of the duodenum. MUC-5AC was expressed in some cases with gastric foveolar cells, but in almost every example of ductal adenocarcinoma with a sensitivity of 96.7%. The pictures are in color and numerous. It would seem necessary to have cell blocks for this test.
6. FISH Detection of t(14;18) in Follicular Lymphoma on Archival Cytology Slides, page 198.
   This article featuring Jeff Richmond, Ronald Bryant, Wini Trotman, Barbara Beatty and John Lunde, is published in this issue of Cancer Cytopathology.

FROM THE ARCHIVES:

The original articles on recognition of lower uterine segment (LUS) in cervical smears appeared about 10 years ago (Peralta-Venturino et al, Diagn Cytopathol 1995 May;12:263-8, and Heaton et al, Am J Clin Pathol 1996;106:511-6) after widespread use of the new generation cervical brushes, which reached higher into the endometrial cavity, particularly after cone biopsies of the cervix. Apart from ciliated columnar cells, the articles emphasized really large, cell dense fragments of glandular epithelium, with branching, and glandular lumina. Occasional endometrial stromal fragments were still attached. The picture had been mistaken for endometriosis and for low grade adenocarcinoma. I suppose one of the reasons we are not still plagued with this differential diagnosis is the use of the ThinPrep processing. The illustrations are interesting to look back on.

Gladwyn Leiman