Treatment outcomes for primary intraocular lymphoma: implications for external beam radiotherapy.

PURPOSE: Intravitreal chemotherapy for primary intraocular lymphoma (PIOL) increasingly is promoted as an alternative to radiotherapy, owing to putative high failure and complication rates of the latter modality. Our aim was to confirm whether these concerns about radiotherapy were borne out in patients treated at our institution over the last decade. DESIGN: Retrospective interventional case series. PARTICIPANTS: A total of 21 eyes of 12 patients with PIOL. METHODS: Comprehensive chart review of ophthalmologic and systemic manifestations, treatments, and outcomes. MAIN OUTCOME MEASURES: Radiation complications and local tumour control. RESULTS: Cytology-confirmed lymphoma involved one eye in three patients and both eyes in nine patients. Initial treatment included external beam radiotherapy and chemotherapy (six patients), chemotherapy alone (four patients), radiotherapy alone (one patient), and no treatment (one patient). Ocular relapses occurred in no patients receiving radiotherapy and in two patients who did not receive radiotherapy. Complications of radiotherapy included dry eye (four patients), cataract (four patients), and mild radiation retinopathy (two patients). CONCLUSIONS: Radiotherapy for PIOL is highly effective with acceptable complications. In the absence of a clear advantage to intravitreal chemotherapy, which involves repetitive injections and associated risks, radiotherapy may still be the most appropriate first-line treatment in most cases.

Transvaginal fine needle aspiration biopsy.

OBJECTIVE: To assess the role of transvaginal fine needle aspiration biopsy (FNAB) in the evaluation of palpable gynecologic masses. STUDY DESIGN: Transvaginal FNABs from 1994 to 1999 were identified from the files of Barnes-Jewish Hospital. Histologic correlation was obtained using the Pathology Department's computer database. Two pathologists reviewed the pathologic samples. Pertinent clinical information was obtained by reviewing the medical records. RESULTS: Twenty-two transvaginal FNABs from 22 patients were studied. The patients' mean age was 59 years (range, 29-84). Most patients (77%) had a previous history of a gynecologic malignancy, and 73% had a previous total abdominal hysterectomy and bilateral salpingo-oophorectomy. The size of the lesion sampled was provided in 15 cases and ranged from <1 to 5.4 cm in diameter. The location of the mass was reported as follows: vaginal (10 cases), vaginal cuff (5), rectovaginal septum (2), cul-de-sac (1), fornix (1), vaginal apex (1), right side of pelvis (1), and not specified (1). The cytologic diagnoses were: negative for malignancy (10 cases), positive for malignancy (9) and unsatisfactory (3). Most cases (77%) had histologic correlation or clinical follow-up. There was one false negative and no false positive cytologic diagnosis. CONCLUSION: Cytologic interpretation of transvaginal FNAB is an effective toolfor the evaluation of palpable pelvic and vaginal masses. Its specificity and sensitivity are 100% and 88%, respectively.

Venoarterial air embolus: a complication of vacuum-assisted venous drainage.

Minimal access techniques with cardiopulmonary bypass use smaller cannula systems for management of cardiopulmonary bypass. To augment flow rates through the smaller cannula, the technique of vacuum-assisted venous drainage has been used. We describe a complication of vacuum-assisted venous drainage by inadvertent positive pressurization of the venous circuit resulting in a paradoxic air embolus across a patent atrial septal defect. Hazards of the current cardiopulmonary bypass systems and techniques for avoiding this potential complication are discussed.

Expression of CD44S and CD44v5 is more common in stage III than in stage I serous ovarian carcinomas.

Experimental evidence suggests that attachment of ovarian carcinoma cells to the peritoneal mesothelium involves the interaction between CD44 on ovarian carcinoma cells and hyaluronic acid on mesothelial surfaces. The authors therefore evaluated local and disseminated ovarian serous carcinomas for the expression of standard CD44 and CD44 splice variants CD44v5, CD44v6, and CD44v7/8. The relative amount of hyaluronic acid (HA) in stroma surrounding tumor nests also was studied. Using immunohistochemistry and archival tissue, 14 serous ovarian carcinomas confined to the ovary (stage I) and 14 serous ovarian carcinomas with peritoneal implants and positive peritoneal fluid (stage III) were stained with antibodies to standard CD44, CD44v5, CD44v6, and CD44v7/8. All tissues also were analyzed for HA using a HA binding peptide. Immunostaining was classified as focal or diffuse and graded from 1 to 4 based on intensity. Immunoreactivity for standard CD44 was seen in 5 of 14 (36%) stage I tumors and 10 of 14 (71%) stage III tumors. Similarly, immunoreactivity with CD44v5 was seen in 2 of 14 (14%) stage I tumors and 9 of 14 stage III tumors (64%). Hyaluronic acid was present in the stroma surrounding all stage I and III tumors, but was more intense in the stroma adjacent to metastatic implants from stage III carcinomas. Tumor cells were uniformly negative for intracellular HA. These results suggest that CD44S and CD44v5 are differentially expressed in early (stage I) and advanced (stage III) ovarian serous carcinomas and support previous studies that suggest a role for CD44 and stromal HA in the dissemination of ovarian epithelial cancer.

Vaginal intraepithelial neoplasia and the Pap smear.

OBJECTIVE: To assess the sensitivity of the vaginal smear cytologic examination in detecting vaginal intraepithelial neoplasia (VAIN) and to evaluate the cytologic findings of cases of VAIN. STUDY DESIGN: Cases with a histologic diagnosis of VAIN were identified from the Barnes-Jewish Hospital South and North Campus over a period of five and nine years, respectively. Only posthysterectomy patients with a tissue biopsy diagnosis of VAIN and with a vaginal smear obtained within three months of the biopsy were included in the study. Pertinent clinical information was obtained by reviewing the medical records. Two pathologists reviewed the pathologic samples. RESULTS: Thirty-five vaginal smears from 31 posthysterectomy patients were included in the study. The mean age was 57 years (range, 29-84). The cytologic diagnoses of smears from patients with VAIN included: high grade squamous intraepithelial lesion (19 cases), low grade squamous intraepithelial lesion (10 cases), atypical squamous cells of uncertain significance (5 cases) and negative for malignancy (1 case). CONCLUSION: The sensitivity of the vaginal smear cytologic examination in detecting VAIN is 83%. Obscuring inflammation contributed to false negative diagnoses in two cases.

Fine-needle aspiration cytology of mesenchymal hamartoma of the chest wall.

We report on an uncommon entity, the so-called "chest wall chondromatous hamartoma" or "mesenchymal hamartoma of the chest wall" (MHCW), diagnosed by fine-needle aspiration (FNA) cytology in a 6-mo-old boy. Radiologic features were those of an aggressive lesion with rib expansion and destruction, that contrasted with aspirate smears showing bland cartilage and spindled mesenchymal elements. The clinicoradiographic features together with the FNA yield of mixed cellular elements aided in the correct diagnosis of MHCW.

Pulmonary fine needle aspiration biopsy. Assessing the negative diagnosis.

OBJECTIVE: To assess the significance of the "negative for malignancy" category when applied to pulmonary transthoracic fine needle aspiration biopsy (FNAB). STUDY DESIGN: Transthoracic lung FNABs diagnosed as "negative for malignancy" were identified from the files of Barnes-Jewish Hospital's South and North Campus over a period of five and nine years, respectively. Histologic correlation and clinical follow-up were obtained. RESULTS: Of the 1,181 lung FNABs performed during the study period, 108 cases (9%) had a negative cytologic diagnosis. Histologic correlation was available in 46 cases (43%), of which 23 cases had benign histologic findings, and 19 cases were malignant. Thirty-five of the 62 cases without histologic correlation had clinical follow-up consistent with a benign process. CONCLUSION: Based on the histologic correlation and clinical data available, the negative predictive value was 77%. Inadequate sampling was responsible for all false negative cytologic diagnoses in this series.

Role of cytopathology in the diagnosis of ocular malignancies.

OBJECTIVE: To determine the positive predictive value of ocular cytologic specimens and to describe the cytopathologic findings encountered in ocular samples from patients with intraocular neoplasms. STUDY DESIGN: Intraocular fluids and ocular fine needle aspirates (FNAs) cytologically diagnosed as either suspicious or positive for malignancy during a 15-year period were reviewed, and follow-up was obtained. RESULTS: Seventeen patients with intraocular samples diagnosed as suspicious or positive for malignancy (9 vitreous, 6 anterior chamber, 3 FNAs) were identified. The mean patient age was 58 years (range, 3-91). Cytologic diagnoses included: lymphoma (5), suspicious for lymphoma (2), melanoma (6), suspicious for melanoma (2), carcinoma (2) and retinoblastoma (1). Clinical and/or surgical follow-up was available in 12 cases and was consistent with the presence of malignancy in all but one case, which proved to be fungal endophthalmitis. One of two patients with a cytologic diagnosis of carcinoma had melanoma on follow-up. Cytologic samples suspicious or positive for lymphoma showed single, large cells with scant cytoplasm and prominent nucleoli. Cytologic samples suspicious or positive for the epithelioid type of melanoma showed loosely cohesive groups or single cells, marked cellular pleomorphism, large nucleoli, scant to moderately abundant cytoplasm and variable amounts of melanin. Cytologic samples from spindle cell melanomas showed spindle cells without nuclear or cellular pleomorphism, without hyperchromasia, and with inconspicuous nucleoli and occasional nuclear grooves. Loose aggregates of small cells with hyperchromatic nuclei and scant cytoplasm characterized the retinoblastoma samples. CONCLUSION: The positive predictive value of intraocular fluid cytology was 92%. Reactive lymphoid processes may be difficult to differentiate from lymphoma and epithelioid melanoma from carcinoma in intraocular cytologic specimens.

Another quality assurance issue--amended reports: what do we really know about them?

The Clinical Laboratory Improvement Amendment (CLIA) of 1988 requires that if a cytology/histology discrepancy is discovered which is significant and affects patient care, an amended report should be issued (Clinical Laboratory Improvement Amendments, Fed Reg 1992;57:7169). Since little is known about such amended reports, a survey was developed to assess how individuals handle discrepancies. The Quality Assurance Task Force from the Papanicolaou Society of Cytopathology created a survey to assess these methods and sent it to all of their members. Fifty-one individuals responded to the survey. Methods vary widely among institutions. On average, 107 cytologic/histologic correlations are performed each month with the discovery of approximately 2 major and 11 minor discrepancies. Thirty-nine responders utilize written amended reports and telephone clinicians when a major discrepancy is found. Thirty-eight individuals indicated that their place of employment has a written policy concerning discrepancies. Time spent in quality assurance issues averaged 8 hr per wk for cytotechnologists and 3 hr per wk for pathologists. Although amended reports are required when significant discrepancies are revealed, a standard practice does not exist.

Glandular cells in vaginal smears from posthysterectomy patients.

OBJECTIVE: To assess the significance of nonatypical glandular cells in vaginal smears from patients who had undergone total hysterectomy. STUDY DESIGN: Vaginal smears with nonatypical glandular epithelium obtained from post-total hysterectomy patients were identified in our files over a 4.5-year period. The cytologic findings were correlated with the clinical data. RESULTS: Smears with nonatypical glandular epithelium from 15 post-total hysterectomy patients were identified, making this the largest series in the literature. The patients' mean age was 59 years. Most patients (73%) had a history of gynecologic malignancy, and 60% had received radiotherapy. All patients had a normal gynecologic examination when the vaginal smear was obtained. None of the patients developed recurrent or de novo vaginal adenocarcinoma. CONCLUSION: The presence of nonatypical glandular epithelial cells in smears from total hysterectomy patients is not indicative of adenocarcinoma.

Hyalinizing trabecular adenoma of the thyroid. A report of two cases with cytologic, histologic and immunohistochemical findings.

BACKGROUND: Hyalinizing trabecular adenoma (HTA) is a rare benign thyroid tumor that is easily confused with medullary carcinoma on surgical specimens and with papillary carcinoma on cytologic specimens. CASES: The fine needle aspiration biopsies (FNABs) and surgically resected specimens from two patients with HTA were studied. Nuclear grooves and nuclear pseudoinclusions were identified in both FNABs. Gross examination of the surgical specimens revealed two nodules (0.8 and 0.5 cm in diameter) in one case and a 6-cm nodule in the other. A thin, fibrous capsule surrounded each nodule. A predominant trabecular pattern was observed in the three lesions. Antibodies to thyroglobulin, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), vimentin, chromogranin, synaptophysin, neuron-specific enolase, proliferating cell nuclear antigen (PCNA), Ki-67 and p53 were used to stain 10% buffered, formalin-fixed, paraffin-embedded sections of the surgical specimens. No immunostaining was observed with antibodies against calcitonin, synaptophysin, chromogranin, EMA, vimentin or p53. Less than 5% of cells were CEA positive in one case. The Ki-67 index was low and PCNA expression high. CONCLUSION: HTAs occur as solitary or multiple nodules. FNABs of HTAs contain cells with nuclear grooves and nuclear pseudoinclusions but lack psammoma bodies, high cellularity and papillary structures. Immunohistochemistry using anticalcitonin and antithyroglobulin antibodies is helpful in distinguishing these tumors from medullary carcinoma. The low Ki-67 index and absence of p53 immunostaining are consistent with the benign behavior of this tumor. The significance of high PCNA immunostaining is uncertain.

Intraoperative transesophageal echocardiography and epiaortic ultrasound for assessment of atherosclerosis of the thoracic aorta.

OBJECTIVES: This study sought to determine the role of transesophageal echocardiography (TEE) and epiaortic ultrasound in the detection of atherosclerosis of the ascending aorta in patients undergoing cardiac surgery. BACKGROUND: Atherosclerosis of the ascending aorta is a major risk factor for perioperative stroke and systemic embolism in patients undergoing cardiac surgery. METHODS: Forty-four patients underwent prospective evaluation of the ascending aorta with two ultrasound techniques-epiaortic ultrasound and biplane TEE-and by palpation. The severity of atherosclerosis was graded on a four-point scale as normal, mild, moderate or severe. RESULTS: A comparison of results with biplane TEE and those with epiaortic ultrasound yielded a kappa value of 0.12 (95% confidence interval 0 to 0.25), indicating poor correlation between the two. Compared with epiaortic ultrasound, biplane TEE significantly underestimated the severity of ascending aortic atherosclerosis, and this underestimation was more marked in the distal ascending aorta (p < 0.0001). When compared with epiaortic ultrasound and biplane TEE, palpation of the ascending aorta significantly underestimated the presence and severity of atherosclerosis (p < 0.0001 for both). CONCLUSIONS: Epiaortic ultrasound is more accurate than TEE for identification of atherosclerosis of the ascending aorta, but both ultrasound techniques are superior to palpation. Epiaortic ultrasound and TEE provide complementary information regarding thoracic aortic atherosclerosis. Modification of surgical technique on the basis of results of intraoperative epiaortic ultrasound and TEE in elderly patients undergoing cardiac procedures may prevent atheroembolic complications.

Nuclear pseudoinclusions in a case of parotid mucoepidermoid carcinoma.

Mucoepidermoid carcinoma is a common malignant salivary gland tumor characterized by cellular and architectural heterogeneity. Nuclear pseudoinclusions have not been previously described in this salivary gland tumor. This is a description of the cytologic and histologic findings of a parotid mucoepidermoid carcinoma with nuclear pseudoinclusions.

In situ hybridization of human erythropoietin in pre- and postnatal kidneys.

Due to the transient transcription of the gene of erythropoietin (EPO) in response to hypoxic stimuli, localization within the cell of origin in humans has not been possible. Under acutely induced transcription of the EPO gene, through severe bleeding (hematocrit < 10%), EPO transcripts were detected within renal interstitial cells in rodents. However, by immunohistochemistry or tissue culture, human tubular epithelial cells or glomerular mesangium have been shown to produce EPO, suggesting a species difference. Aiming to investigate the precise location of EPO in intact human kidneys, 38 fetal, infant, and adult kidneys were examined by in situ hybridization. Kidneys from patients with conditions predisposing to severe hypoxia and/or induced polycythemia were utilized, because under these conditions active EPO mRNA synthesis is expected. We found specific EPO mRNA transcripts within a small population of cortical interstitial cells of near-term or postnatal kidneys.

Ontogeny of type I procollagen expression during human fetal lung development.

The cellular sites of type I procollagen (PCI) production were investigated during fetal and early postnatal human lung development. PCI-synthesizing cells and sites of recent collagen deposition were visualized by immunoperoxidase staining of lung tissue with monoclonal antibodies to human PCI. In selected cases, serial sections were also examined by in situ hybridization to establish the cellular sites of PCI gene expression and mRNA accumulation. PCI cytoplasmic immunostaining generally correlated with sites of mRNA accumulation and with known sites of interstitial collagen deposition, including the adventitial and muscular layers of large blood vessels, submesothelial and peribronchial connective tissue, perichondrium, and interstitial matrix. However, we also observed developmental changes in relative PCI expression for each of these compartments, heterogeneity in the level of PCI expression by cells within individual anatomic subcompartments, and variations in the level of PCI expression along the length of pulmonary blood vessels and airways. These studies emphasize the complexity of developmentally regulated alterations in procollagen production during lung development.

Cytology of benign cystic uterine adnexal masses.

The findings from a cytologic examination of 26 surgically removed cystic adnexal masses (1-11.5 cm) aspirated with a 22-gauge needle were correlated with the histopathologic findings. The mean age of the patients was 48 years. Examination of the Papanicolaou-stained cytospin preparations showed that all but three were cellular. Benign epithelial cells were identified in fluid aspirated from the mass from one patient with hydrosalpinx and from three with paramesonephric and one with simple cysts; they were also found in aspirated samples from three patients with serous cystadenoma and one with serous cystadenofibroma. Masses from the five patients with follicle cysts and cystic follicles contained numerous granulosa cells. Ciliated cells or ciliated cytoplasmic fragments were found in all aspirated samples except those from patients with follicle cysts, cystic follicles or endometriosis. In two patients, one with endometriosis and one with serious cystadenoma, the epithelial cells were atypical, with a high nuclear/cytoplasmic ratio, hyperchromasia, nuclear molding and large nucleoli. These results could be misinterpreted as indicating malignancy. In summary, the vast majority of aspirated samples (91%) contained benign cells. However, caution should be exercised in the interpretation of possibly misleading cytologic findings in patients with endometriosis or cystadenoma.

Role of mesothelial and submesothelial stromal cells in matrix remodeling following pleural injury.

The pleural response to injury is a complex and poorly understood multifactorial process that can result in the development of fibrosis or obliteration of the pleural space. Pleural fibroblasts are considered the main source of extracellular matrix but cell culture studies have demonstrated synthesis of matrix components by mesothelial cells. We assessed the mesothelial cell contribution to extracellular matrix during pleural healing using immunohistochemical technique. Paraffin-embedded tissue of 3 normal adult lungs and 7 adults with active pleuritis were studied using monoclonal antibodies to cytokeratin, type IV collagen, vimentin, and type I procollagen (PCI). Normal pleural had a single layer of cytokeratin-positive and PCI-negative mesothelium over a thin, continuous type IV collagen-positive basement membrane and PCI-negative submesothelial stroma. Areas of active pleuritis showed loss of the continuous linear staining with anti-type IV collagen antibody. Coexpression of cytokeratin, vimentin and PCI was identified in spindle and/or cuboidal cells located in the fibrin layer, submesothelial connective tissue layer, or on the pleural surface. These findings suggest that reactive mesothelial cells play an active role in the production of extracellular matrix during pleural injury, and that disruption of the submesothelial basement membrane is a key event in determining subsequent fibrous organization of pleural exudate.

Multilocular renal cyst. Immunohistochemical and lectin-binding study.

Multilocular renal cyst is an uncommon lesion of uncertain pathogenesis seen in children and adults. We report the immunohistochemical and lectin-binding profiles of three MRC occurring in adults. All cases had strong and uniform cytoplasmic staining of lining epithelial cells for keratin and binding sites for arachis hypogaea lectin, similar to that seen for the distal convoluted tubules or collecting ducts in normal kidney. However, we found variable expression of other distal nephron markers, including epithelial membrane antigen and Ber-EP4. Furthermore, lining cells in some lesions coexpressed proximal nephron markers such as alpha-1-antitrypsin and lysozyme, as well as binding sites for lotus tetragonolobus lectin. Immunostaining for type IV (basement membrane) collagen demonstrated a continuous subepithelial basement membrane zone and basal laminae surrounding desmin-positive stromal cells. Areas of active collagen synthesis and stromal procollagen deposition were visualized within the interlocular septae using a monoclonal antibody to type I procollagen. Significant proliferative activity was not detected in the lining epithelium or stroma using the anti-proliferating cell nuclear antigen. In conclusion, MRC show aberrant tubular epithelial glycoprotein and glycoconjugate expression, low proliferative activity, and associated activation of interlocular stromal cells.