James L. Finley

The role of fine-needle aspiration biopsy in the rapid diagnosis and management of thyroid neoplasm.

This report describes our 5‐year experience with fine‐needle aspiration (FNA) biopsy of the thyroid in a 560‐bed teaching hospital. Three hundred nine FNA biopsies were performed primarily by one endocrinologist and interpreted by several pathologists. Analysis of the data reveals the sensitivity of the procedure is 93%, specificity is 95.1%, and the positive and negative predictive values are 88.9% and 96.5%, respectively. This data confirms the diagnostic accuracy of FNA biopsy. Complications were seen in 6 of 309 cases (1.9%) and were relatively mild. Nearly 75% of the cases in the series were cytologically diagnosed as nonneoplastic. Fine‐needle aspiration biopsy identified 19.4% of the cases needing surgery, of which 72% had neoplastic nodules, confirming the selection role of the procedure. The management of thyroid nodules is discussed and a selective review of the FNA literature is presented. The authors believe that our experience rebuts the argument that special referral centers are needed to interpret the cytologic material. Several well trained surgical pathologists can become proficient in interpreting the FNA biopsies without significant loss in accuracy, and thereby render a definite diagnosis in the vast majority of the cases. Accordingly, the authors recommend FNA of the thyroid as the initial diagnostic test in the evaluation of thyroid nodules.

Renal vascular smooth muscle proliferation in neurofibromatosis

An unusual vascular lesion was seen in a 14-year-old white boy with renal vascular hypertension and neurofibromatosis. Microscopically, nodular intimal and medial proliferations of spindle-shaped cells involved arteries, arterioles, and veins of all caliber within the renal parenchyma. Immunoperoxidase studies indicated these cells to have characteristics of smooth muscle, and this finding was confirmed by ultrastructural examination. Despite the generalized nature of the process in the biopsy sample, the patients hypertension responded well to surgical treatment.

Large-bore feeding tube occlusion by yeast colonies

This is a first report of three patients with silicone feeding tubes (two with percutaneous endoscopic gastrostomies and one with a jejunostomy, all 20 French catheters) that have formed a thick yeast crust on the inner luminal surface causing tube occlusion in two cases. Candida species were isolated in all three tubes. The yeast crust could not be removed with a brush or with fungicidal drugs such as nystatin and amphotericin B. Histologic sections through these feeding tubes revealed yeast penetration through the silicone material, explaining the adherent nature of the crust. This complication may also explain the observed material deterioration with subsequent breakage.

Monoclonal antibody DS6 detects a tumor‐associated sialoglycotope expressed on human serous ovarian carcinomas

A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre‐treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase‐sensitive and periodic acid‐sensitive sialic acid glycoconjugate (“sialoglycotope”). SDS‐PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non–disulfide‐linked glycoprotein containing N‐linked oligosaccharides. Two‐dimensional non‐equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double‐label, 2‐color immunohistochemical studies. The DS6‐detected CA6 antigen appears to be distinct from other well‐characterized tumor‐associated antigens, including MUC1, CA125 and the histo‐blood group–related antigens sLea, sLex and sTn. Int. J. Cancer 88:866–872, 2000.

Diagnosis of mastocytosis by fine-needle aspiration cytology

We report a case of a 28‐yr‐old man in whom mastocytosis was diagnosed by fine‐needle aspiration (FNA) of enlarged periaortic lymph nodes. FNA cytology revealed numerous mast cells characterized by cells having round to oval eccentrically placed nuclei and associated coarsely granular cytoplasm, most conspicuous on Diff‐Quik‐ and Giemsa‐stained smears. Lymphocytes, histiocytes, and occasional plasma cells were present in the background. We believe this paper to be the first reported case of mastocytosis diagnosed by FNA. The case demonstrates the utility of FNA in evaluating lymphadenopathy occurring in mastocytosis. Diagn. Cytopathol. 1998;18:368–370.

Immunohistochemical distribution of tumor-associated antigen CA6 in gynecological neoplasms as detected by monoclonal antibody DS6.

DS6 is a murine monoclonal antibody developed using ovarian papillary serous adenocarcinoma as the immunogen. DS6 immunohistochemically reacts with a tumor-associated antigen, CA6, which has a limited range of expression in normal human tissues and is not expressed by benign mesothelium. We have studied the spectrum of immunohistochemical reactivity of antibody DS6 in 293 formalin-fixed, paraffin-embedded human gynecological neoplasms. The CA6 antigen shows strong expression in serous adenocarcinomas of the ovary (56/58 cases) and endometrium (6/6). CA6 is also expressed by the majority of ovarian endometrioid adenocarcinomas and Brenner tumors and by the majority of endometrioid adenocarcinomas, mucinous adenocarcinomas, and clear cell adenocarcinomas of the endometrium. CA6 is detected in 14% of ovarian clear cell carcinomas and is not detected in ovarian mucinous cystadenomas (0/7), mucinous intestinal-type borderline tumors (0/8), mucinous adenocarcinomas (0/10), or in malignant mesotheliomas (0/8). In neoplasms with papillary or glandular growth patterns, CA6 is detected along luminal cell membranes. CA6 is also seen along peripheral cell membranes and focally in the cytoplasm in some epithelial neoplasms. There is heterogeneity in immunohistochemical staining for DS6 both within an individual neoplasm and between neoplasms. Reactivity is not detected in neoplasms of sex cord-stromal, mesenchymal or germ cell origin.

Desmosomes and Microvilli Mean a Lot: Diagnosis of Neoplasms of Unknown Origin Using Electron Microscopy

Neoplasms of unknown origin present a difficult diagnostic dilemma, particularly if they are very poorly differentiated. Adenocarcinomas, squamous cell carcinomas, melanomas, lymphomas, and sarcomas can all be very difficult to diagnose if the light microscopic cytomorphology is sufficiently undifferentiated. Electron microscopy (EM) can either demonstrate differentiation or narrow the range of differential diagnoses. The authors report the case of a 64-year-old male who has been HIV positive for several years and was found to have expansile lytic lesions in several ribs and a thumb fracture associated with a soft tissue mass which was biopsied. The tumor was composed of very pleomorphic malignant cells without specific differentiation. The malignant cells stained positive for pancytokeratin (AE 1/3), EMA, CEA, CK20, and CK7. Rare cells had mucicarmine-positive intracytoplasmic droplets. They were negative for S-100, calretinin, CD45, MART-1, and vimentin. EM revealed intracytoplasmic lumina with long microvilli and many well-formed desmosomal junctions. The diagnosis was initially very broad. Immunohistochemistry narrowed the diagnosis to carcinoma, but EM alone was able to narrow the diagnosis to poorly differentiated adenocarcinoma. In a neoplasm of unknown origin, EM can either narrow the differential significantly or, in the case of limited material, provide information that otherwise may not be attainable.

Ornithine decarboxylase activity during gastric ulcer healing in dogs

Ornithine decarboxylase (ODC) activity has been associated with mucosal growth and injury, yet, little information is available on ODC activity during gastric ulcer healing. We measured ODC activity in the ulcer base submucosa and the surrounding mucosa at 1 cm and 2 cm and assessed ulcer surface healing and a histologic score in experimentally induced ulcers (Quinton ulcer-maker) at 0 and 5 hr and at one, two, three, four, and seven days. A total of 26 dogs were studied, eight of which received 2% difluoromethylornithine (DFMO, a specific inhibitor of ODC) in drinking water. Ulcer healing was assessed by digitizing initial (plug size), and final ulcer surface area and was expressed as percent ulcer surface reduction. A histologic score was assessed by two independent pathologists unaware of the treatment. ODC induction was observed in the submucosa of the ulcer base but not in the surrounding mucosa. The baseline submucosal ODC activity was measured at 0.2±0.1 pmol (14CO2)/mg protein/hr, and at one day the ODC activity increased to 4.0±0.7, at three days to 15.2±5.5, and at seven days to 2.6±1.0 (P<0.001). DFMO treatment delayed GU healing significantly up to three days, but no difference was noted at seven days. The assessed histologic parameters did not correlate with ODC activity, and DFMO treatment did not alter the histologic score. These data suggest that polyamine biosynthesis occurs in the ulcer base submucosa during the first seven days of experimentally placed gastric ulcers. Suppression of ODC activity with DFMO delays ulcer surface reduction during the first three days, but the significance of ODC induction and polyamine biosynthesis during early ulcer healing remains in question.

The spectrum of immunohistochemical reactivity of monoclonal antibody DS6 in nongynecologic neoplasms.

DS6 is a murine monoclonal antibody that was developed using ovarian serous adenocarcinoma as immunogen. DS6 reacts immunohistochemically with a tumor-associated antigen, CA6, which has only a limited range of expression in normal human tissues. CA6 is most characteristically expressed in type II pneumocytes, fallopian tube epithelium, and urothelium, but lacks expression in mesothelium. The authors recently reported the spectrum of reactivity of DS6 with a wide variety of neoplasms of the gynecologic tract and found DS6 to be highly characteristic of serous neoplasms. CA6 is also expressed in other müllerian-derived epithelial neoplasms of the gynecologic tissues, but is not typically expressed by ovarian intestinal-type mucinous neoplasms, mesothelioma, mesenchymal neoplasms, ovarian germ cell tumors, or sex cord-stromal neoplasms. In this study, the authors tested the monoclonal antibody DS6 with 1,202 nongynecologic neoplasms to characterize the full range of expression of antigen CA6. This study has shown that CA6 is highly expressed by many carcinomas of breast, pancreas, and urothelium, and also shows expression in some carcinomas of renal and pulmonary origin, and some neoplasms of other sites. DS6 immunoreactivity is not seen in the majority of neoplasms with hematopoietic, mesenchymal, or germ cell differentiation.

Gastric ulcer healing after laser treatment in dogs

Endoscopic laser photocoagulation of ulcers is increasingly used to produce hemostasis in patients who are actively bleeding or in patients with stigmata of recent hemorrhage. Little information is available describing ulcer healing rates after laser treatments. The aim of this study was to compare the healing rates of gastric ulcers treated with laser energy (Nd:YAG) with untreated ulcers in dogs. Two standard gastric ulcers (12–14 mm diameter) were created in each dog stomach using an ulcer maker (Quinton) under endoscopic guidance and one was randomly selected for laser treatment (L), while the other served as control (C). Ten laser spots were applied circumferentially around the ulcer crater with a mean energy of 595 J per ulcer. Ten dogs were studied; four of which were sacrificed after one week and six after two weeks. Healing of treated ulcers was compared with that of control ulcers and expressed as a percentage of the initial ulcer surface. Histologic injury and reepithelialization were scored by two pathologists unaware of the treatment. Laser-treated ulcers healed significantly slower than untreated ulcers at one week (53% L vs 94% C), P<0.05 and histologic injury was greater in ulcers treated with laser photocoagulation. At two weeks, only 82% of the lasertreated ulcer surface was healed in comparison with 94% (P<0.05) healing in untreated ulcers, although the mean histologic injury score was not different at two weeks. Reepithelialization was decreased both at one week (11% L vs 71% C), P<0.01) and at two weeks (75% L vs 100% C, P<0.01). This study suggests that ulcer healing may be delayed following endoscopic laser photocoagulation. Further studies are indicated in patients to ascertain whether YAG laser treatment or other coagulation methods delay healing or make ulcers bigger compared with standard medical treatment without coagulation.