Intermediate filaments in endometrial and endocervical carcinomas. The diagnostic utility of vimentin patterns.

We examined the distribution of high- and low-molecular-weight cytokeratins, vimentin, and carcinoembryonic antigen (CEA) in normal endometrial glands and endocervical glands (20 cases each) and in endometrial and endocervical adenocarcinomas (29 cases and 15 cases respectively). Low- and high-molecular-weight cytokeratin staining was present in normal endometrial and endocervical epithelium and in carcinomas. Coexpression of vimentin and cytokeratin was universally present in normal proliferative endometrial glands, with marked decrease or absence of vimentin staining in secretory phase patterns. Vimentin staining had a perinuclear distribution within the cells, in contrast to the cytokeratins, which stained diffusely. Vimentin was found in only 65% of endometrial adenocarcinomas. Staining was typically focal as well as regional in portions of the tumors. Vimentin was never observed in normal or neoplastic endocervical epithelium. Ultrastructural studies corroborate the perinuclear vimentin immunostaining pattern we observed in endometrial adenocarcinomas. CEA staining results were similar to those previously reported. These data indicate that the presence of vimentin may readily distinguish endometrial from endocervical carcinoma and is diagnostically useful in the study of metastatic adenocarcinomas.

Localized primary (AL) amyloid tumor of the breast. Cytologic, histologic, immunocytochemical and ultrastructural observations.

Two examples of localized primary amyloid tumor of the breast are presented, including one patient with metachronous bilateral lesions. Our findings and review of the literature indicate that this rare lesion occurs predominantly in elderly females and can be mammographically and clinically confused with carcinoma. Fine-needle aspiration biopsy can be a useful procedure to make a preliminary diagnosis. Congo red staining with prior potassium permanganate incubation confirmed the AL type of amyloid in our two cases; this might be the predominant type in the localized form involving the breast. Immunofluorescence studies demonstrated IgA, with kappa and lambda light-chain deposition within the amyloid foci in one case, and intracytoplasmic IgG with both light chains within plasma cells and amyloid deposits of the second case. Ultrastructural examination of one of the cases showed characteristic findings of straight, nonbranching fibrils of 4-9 nm, diagnostic of amyloid. From our findings and a review of the literature, we conclude that amyloid tumors of the breast can occur in three separate settings: secondary amyloidosis, systemic or multiple myeloma associated amyloidosis, and as a localized primary type having a benign course.

Systematization of primary histopathologic and fine-needle aspiration cytologic features and description of unusual histopathologic features of neuroblastic tumors: a report from the Pediatric Oncology Group.

On the basis of a detailed review of the primary histopathologic features of 239 cases and the fine-needle aspiration cytologic features of seven cases, a systematized schema of differentiation, progressive maturation and organization, and biologic behavior in neuroblastic tumors (NTs) is presented. The differentiation is of the gangliocytic and schwannian lineages. Maturation occurs in differentiating neuroblasts, leading to the formation of various stages of ganglion cells and Schwann cells. Organization is characterized by nesting pattern, rosette formation, parallel arrangement of neuropil, and alignment of Schwann cells along the neurites. According to this schema the NTs can be arranged in the following order: undifferentiated, poorly differentiated, and differentiating neuroblastoma; nodular, intermixed, and borderline ganglioneuroblastoma; and ganglioneuroma. Formulation of such a schema is helpful in gaining a better understanding of the complex pathologic features and in defining the criteria for various types of NTs. Therefore, the schema also would be helpful in achieving uniformity and reproducibility of the diagnosis of various types of NTs. Previously unreported features related to shape, size, nucleus, and cytoplasm of neuroblasts; secondary changes and patterns; changes in the fibrovascular septa; and other morphologic aspects of NTs and features (such as large tumor cells, karyorrhectic cells in fine-needle aspiration biopsy, tumor giant cells, anaplasia, and nesting pattern of tumor cells that have not been sufficiently emphasized) also are described. The importance of these previously unreported and insufficiently emphasized features relates to the histologic and cytologic diagnosis of NTs. For example, some of the features, such as starry sky appearance and spindle-shaped neuroblasts, may be misleading if seen in a small biopsy specimen. Others, such as tumor giant cells resembling ganglion cells and nesting pattern, will provide clues to the correct diagnosis. Some of the features, such as sclerosing pattern, hyalinization, and dense lymphoplasmacytic infiltration, may be related to the phenomenon of regression exhibited by neuroblastomas.

Parathyroid hormone (PTH) assay of parathyroid cysts examined by fine-needle aspiration biopsy.

The authors report three cases of parathyroid cysts examined by the fine-needle aspiration biopsy technic. A presumptive diagnosis of parathyroid cyst was made when characteristic water-clear fluid was aspirated. The diagnosis was then confirmed by parathyroid hormone (PTH) assay. The authors believe that the C-terminal/midmolecule determination should be the assay of choice, because the N-terminal-specific assay gave normal or slightly elevated results in all the cases studied. If only an N-terminal-specific PTH assay is obtained, potential for a false negative diagnosis exists. With a correct PTH assay, a specific diagnosis of parathyroid cyst can be rendered, which enables appropriate treatment of total fluid aspiration, which thereby eliminates the need for thyroid hormone treatment or surgery in most cases. A discussion of PTH assays is presented along with speculations concerning the secretion of PTH by the parathyroid gland. The previous literature detailing cytologic findings and the PTH assays of parathyroid cysts diagnosed by the fine-needle aspiration biopsy are reviewed.

The use of immunoperoxidase panels for the cytologic diagnosis of malignancy in serous effusions.

The diagnostic value of an immunoperoxidase panel composed of antisera to carcinoembryonic antigen (CEA), epithelial membrane antigens (EMA), and high- and low-molecular-weight cytokeratins was evaluated on 39 consecutive pleural and peritoneal fluid specimens and correlated with routine cytologic and histochemical studies. The cases were classified into two groups: malignant (epithelial and small-cell undifferentiated carcinomas) and benign effusions. We found that the CEA and EMA antisera identified 91% and 100% of the epithelial malignancies, respectively. Mucin stains were positive in only 41% (mucicarmine) and 59% (Alcian blue) of these cases. The battery of cytokeratin markers identified malignant cells from 45%-100% of the cases but showed considerable positive staining of mesothelial cells. A selective review of the literature is presented along with recommendations for technical improvement in immunoperoxidase studies. We believe that an immunoperoxidase panel can be of considerable value in the cytologic diagnosis of epithelial malignancies in effusions. The panel composed of CEA and EMA can prove helpful in a routine cytology practice. Although the cytokeratin marker identified malignant cells, the concomitant immunostaining of mesothelial cells limits its utility. The commercially available panel can be a potential aid in improving the accuracy of serous fluid cytologic examination by decreasing both false-positive and false-negative diagnoses and thereby helping to prevent delays in diagnosis and treatment.

Small-intestinal brushing cytology in the diagnosis of cryptosporidiosis in AIDS.

We report the cytologic findings of small intestinal brushing material showing cryptosporidiosis in two patients with acquired immunodeficiency syndrome (AIDS). Cryptosporidia measuring approximately 2-4 mu were aligned along the surface of the glandular cells, although many freely dispersed organisms were also present. The differential diagnoses of other structures that could be confused with cryptosporidia are also presented in this article. Small-intestinal brushing cytology may complement endoscopic biopsy in the workup of diarrheal diseases in AIDS, especially in patients with thrombocytopenia, since the bleeding disorder may be a contraindication for endoscopic biopsy.

Psammoma bodies and optically clear nuclei in bronchiolo-alveolar cell carcinoma. Diagnosis by fine needle aspiration biopsy with histologic and ultrastructural confirmation.

The fine needle aspiration cytology of two cases of bronchiolo-alveolar cell carcinoma of the lung having unusual features is reported. One case demonstrated numerous psammoma bodies in the cytologic smears, whereas the other case showed an abundance of cells with optically clear nuclei. Both peripherally located tumors were resected and confirmed as primary bronchiolo-alveolar cell carcinoma by histologic and ultrastructural examination. We believe this to be the first report describing these unusual features of bronchiolo-alveolar cell carcinoma diagnosed by fine needle aspiration cytology. Presented is a discussion of psammoma bodies and optically clear nuclei seen in primary and metastatic tumors of the lung. This will aid in the diagnosis of these cases.

Malignant thymic neoplasms: diagnosis by fine-needle aspiration biopsy with histologic, immunocytochemical, and ultrastructural confirmation.

Two cases of malignant thymic neoplasms diagnosed by transthoracic fine-needle aspiration (FNA) biopsy under fluoroscopic and computerized axial tomography (CT) guidance with histologic, immunocytochemical, and ultrastructural confirmation are presented. The clinical and cytomorphologic features of the first case were typical of a malignant thymoma. A characteristic biphasic cell population of benign epithelial cells and mature lymphocytes was seen in Diff-Quik- and Papanicolaou-stained smears from the anterior mediastinal mass and the paravertebral metastasis and was confirmed by histologic examination. Immunoperoxidase studies for T and B cell subsets demonstrated lymphocytes with the thymic lymphocyte phenotype (Leu 6). Electron microscopic (EM) examination revealed epithelial cells with desmosomal attachments, tonofilaments, and extended cell processes along with mature lymphocytes. FNA biopsy of the second case demonstrated features of a thymic carcinoma. Individually scattered and loosely clustered small groups of markedly anaplastic and pleomorphic large cells were seen both in the Diff-Quik- and Papanicolaou-stained smears. EM performed on the FNA specimen demonstrated the poorly differentiated epithelial nature of the malignancy. The mediastinal mass was partially resected and demonstrated an undifferentiated carcinoma staining positively for low-molecular-weight cytokeratin. Ultrastructure demonstrated cell attachments and relationships consistent with carcinoma. The lack of a lung or other extrapulmonary primary tumor was consistent with a thymic carcinoma. These cases demonstrate the value of performing EM and immunocytochemistry on material obtained by fine-needle aspiration, which can aid in establishing the correct diagnosis and facilitate the clinical management of patients with malignant thymic neoplasms.

Fine needle aspiration cytology of subareolar abscess of the breast. Spectrum of cytomorphologic findings and potential diagnostic pitfalls.

The cytomorphologic findings of eight cases of subareolar abscess of the breast diagnosed by fine needle aspiration (FNA) biopsy are presented. A spectrum of cytologic findings was appreciated, including diagnostic anucleated squames associated with numerous neutrophils, keratinous debris, cholesterol crystals, parakeratosis and strips of squamous epithelium. A foreign-body reaction, with sheets of histiocytes and multinucleated foreign-body-type giant cells, was noted in some of the cases. Potential pitfalls for a false-positive diagnosis of malignancy included the presence of groups of atypical ductal cells, squamous atypia and fragments of exuberant granulation tissue. Seven of the eight cases had complete surgical excision of the lesion, which demonstrated the characteristic findings of dilated lactiferous ducts undergoing squamous metaplasia with rupture and surrounding extensive acute and chronic inflammation with foreign-body reaction. With recognition of the FNA cytologic findings of subareolar abscess of the breast, a specific diagnosis can be rendered, which then allows different treatment modalities depending on the stage of the lesion. Appreciation of the spectrum of cytologic features will enable the pathologist to make the correct diagnosis and thereby avoid potential pitfalls that can possibly lead to a false-positive diagnosis of malignancy.

Fine needle aspiration cytology of tuberculosis of the lumbar vertebrae (Pott's disease).

The cytomorphologic features of tuberculosis of the lumbar vertebra having a granulomatous pattern diagnosed by fine needle aspiration (FNA) biopsy are reported in a 72-year-old woman with a prior history of malignant lymphoma treated by chemotherapy. Cytologic examination revealed microtissue fragments of cohesive cells, including epithelioid histiocytes and scattered, multinucleated Langhans-type giant cells. This is believed to be the first reported case of vertebral tuberculosis (Pott's disease) diagnosed by FNA cytology and confirmed by culture of the aspirate material. This case illustrates the value of FNA cytology in the diagnosis of nonneoplastic skeletal lesions and confirms the value of FNA biopsy the early detection of infectious processes in patients with malignancy.

Ascitic fluid cytology in a case of metastatic malignant mixed mesodermal tumor of the ovary.

The cytologic features of the abdominal fluid from a patient with a malignant mixed mesodermal tumor (MMMT) of the ovary are presented. Both malignant epithelial and stromal elements were cytologically appreciated and confirmed by histologic examination. Other ovarian neoplasms that can present with malignant sarcomatous elements or mixed epithelial and sarcomatous elements are discussed; this case documents the importance of recognizing these features when staging patients with unusual ovarian neoplasms. To our knowledge, this is the first complete report of the ascitic fluid cytology of an MMMT of either ovarian or uterine origin.

The triage role of fine needle aspiration biopsy of palpable breast masses. Diagnostic accuracy and cost-effectiveness.

A total of 219 fine needle aspiration (FNA) biopsies of the breast were performed during the period 1983 to 1985 at a tertiary medical center. The series consisted of 215 women (98.2%) and 4 men (1.8%), with an are range of 14 to 90 years (mean of 46.5 years). Histologic confirmation (93 cases) or clinical follow-up for up to two years was obtained. The sensitivity of the FNA procedure was 82.2%, its specificity was 98.8%, and the overall efficiency of the test was 95.4%. The false-negative rate was 4.4%, with no false-positive diagnoses for the primary diagnosis of breast carcinoma. We have found that one of the major advantages of FNA biopsy is that it lowers costs by allowing the surgeon to triage which patients should have an outpatient excisional biopsy under local anesthesia and which patients should have a one-stage inpatient procedure with frozen section confirmation. For this triage role, suspicious diagnoses (3.2%) were included in the positive group and atypical (1.8%) and insufficient diagnoses (6.8%) in the negative group. Taking into account the FNA biopsy cost of $75, the procedure resulted in a savings per case of $262 over the cost that would have occurred if all cases had had routine inpatient biopsy and $154 per case over the cost that would have occurred with routine outpatient biopsy of all cases. Our results indicate that FNA breast biopsy is a diagnostically accurate and economical triage procedure, even when followed by an excisional or frozen-section biopsy for confirmation. The use of FNA biopsy could be expanded to a greater number of medical centers and decrease the potential for false-positive diagnoses by combining FNA biopsy with frozen-section confirmation.

Diagnostic accuracy and role of immediate interpretation of fine needle aspiration biopsy specimens from various sites.

A statistical analysis of the accuracy of the immediate interpretation of 425 fine needle aspiration (FNA) biopsies from various sites was performed. Preliminary interpretation of Diff-Quik-stained smears was rendered within a few minutes after performing the FNA biopsy, using diagnostic terminology similar to that of a surgical pathology report. The immediate assessment was documented in the formal cytology report and compared to the final diagnosis. For the entire series, the immediate interpretation had a sensitivity of 96%, a specificity of 97%, a positive predictive value (PV) of 98%, a negative PV of 95% and an efficiency of the test of 96%. There were 14 false-negative or falsely insufficient immediate interpretations and one false-positive immediate diagnosis. The diagnostic accuracy of the immediate interpretation of FNA biopsies from specific sites was also calculated; FNA biopsies of the pancreas were the least accurate procedure, having a sensitivity of 60% but a specificity of 100%. The role of the immediate interpretation of FNA biopsies is similar to the use of frozen sections in surgical pathology. An immediate assessment can (1) determine whether an adequate specimen is present, (2) render a specific preliminary diagnosis, (3) guide further clinical investigations or treatment, and (4) determine whether ancillary studies are needed to make a more accurate or specific diagnosis from the FNA specimen. Our results indicate that the immediate interpretation of FNA biopsies is an accurate procedure that should be routinely employed.

The U.S. Transuranium Registry report on the 241Am content of a whole body. Part I: Introduction and history of the case.

The first whole-body analysis of the U.S. Transuranium Registry was initiated in 1979. The donor was a 49-yr-old male Caucasian radiochemist who died of metastatic malignant melanoma. The donor had a recognized, longstanding 241Am internal deposition first identified in a routine urine sample in 1958. A summary of the clinical and postmortem findings is presented with the chronologic sequence of the procedures.

Response of the small intestine to the application of a hypertonic solution.

The morphologic and functional alterations caused by a commonly used hypertonic radiographic dye (Hypaque(R)-50%) were compared with changes observed during the absorption of 150 mM saline in closed segments of the ileum of 2- to 3-kg rabbits. Hypertonic dye caused a rapid decrease in height and width of the villi, a decrease in height of the epithelial cells and closure of the intercellular space. Concomitantly, the tissue fluid content of the bowel wall and the volume of venous outflow from the segment of ileum decreased, presumably in response to the osmotic gradient between ileal lumen and blood. The fluid added to the luminal contents was hypotonic and contained sodium, potassium, chloride and bicarbonate. In contrast, the ileum exposed to 150 mM saline had prominent intercellular spaces between adjacent epithelial cells and absorbed the solution at isotonic conditions. These studies indicate that production of diarrheal fluid by this hypertonic solution is different from that reported for enteric pathogens.

The use of inhibitors of platelet activation or protease activity in platelet concentrates stored for transfusion.

During storage of platelet concentrates the platelets show signs of activation, and extracellular protease activity becomes evident in the plasma. The consequences of platelet activation and plasma protease activity are potentially detrimental to the preservation of platelet function in vitro. The earlier use of prostaglandins during preparation of platelet concentrates to increase the harvest of platelets from whole blood did little to improve their shelf-life. Other compounds that sustain elevated cyclic AMP levels or that directly inhibit platelet agonists provide more effective inhibition of platelet activation during storage. Also, the inclusion of general or specific protease inhibitors appears to improve platelet preservation over extended storage periods. These studies demonstrate the possibility of prolonging the shelf-life of platelet concentrates stored at 22 degrees C through the addition of non-toxic formulations of inhibitors of platelet activation and protease activity.