Ibrahim Ramzy

Cell Preparation Methods Standardized fixation and optimal staining Sampling of cervix, sampling error, homogenization of sample, subsampling Assessment of liquid-based preparations: efficacy and economic impact Training and transitional procedures before full implementation of new technologies Criteria for Sample Adequacy Clinician responsibility for collecting and providing representative sample to laboratory Collection instruments, number of slides Cellular content of samples: evidence of transformation zone (TZ) sampling, number of squamous cells present, obscuring factors Screening issues CONSENSUS POSITION The conventional cervical smear remains the standard method of cervical cancer screening but has limitations in individual test sensitivity and specificity. Sample takers should: (1) receive appropriate training in sample collection, (2) be held responsible for providing the laboratory with appropriate samples, and (3) have their performance monitored. The instruments used for sampling should collect cells from both the ectocervix and endocervix; optimally, TZ sampling, represented by the presence of endocervical or squamous metaplastic cells, should be identifiable in samples other than atrophic specimens. The adequacy of a specimen (as judged microscopically) does not guarantee that it is representative of the cervix. Each cytology report should include a comment on cellular content/adequacy of the specimen. Liquid-based preparations may overcome many of the inherent problems with the conventional cervical smear. We need further data on the cost-effectiveness of making two slides from cervical specimens and/or using two samplers rather than a single one. Do we have enough information to make recommendations as to the appropriate type of sampler to be used in particular situations, such as routine screening? What is the best method of screening for/detecting endocervical glandular neoplasia? How are such terms as unsatisfactory and inadequate defined in cervical cytology classifications other than the Bethesda System? What number and types of epithelial cells should be present (visualized) in a cervical smear or liquid-based preparation for it to be considered adequate? Do we need to have evidence of TZ sampling in specimens taken during the follow-up period after treatment of squamous intraepithelial lesion or after detection of endocervical glandular neoplasia? What criteria for obscuring factors, such as blood and inflammation, should be used in assessing adequacy? Cost-benefit analyses of utilizing liquid-based preparations are needed. Should we inform women about the technical details of the test methods available or chosen by the laboratory? Are women in a position to decide which method is the most appropriate to assess their cervical scrape sample? We need to obtain more information about the properties of proprietary liquid fixative/transport media with respect to inactivation of viral pathogens, tuberculosis and other bacterial pathogens and suitability for immunobiologic and molecular tests, etc. We need to obtain more information on the use of stoichiometric stains and the limitations of Papanicolaou stain for image analysis systems. The use of liquid-based preparations for nongynecologic cytopathology and ancillary tests must be considered, including criteria for adequacy. We need to obtain more information on the time required for and best methods of training experienced cytotechnologists to become competent at assessing liquid-based cervical preparations.

To determine the validity and reproducibility of various cytologic criteria as discriminators between different glandular lesions of the cervix. Seventy-three cervicovaginal smears with glandular lesions and a documented histologic and/ or clinical correlation were studied. The lesions included reactive changes, low grade glandular intraepithelial lesion (LGIL) (encompassing endocervical glandular dysplasia), high grade glandular intraepithelial lesion (HGIL) (encompassing adenocarcinoma in situ) and invasive adenocarcinoma (IA). Twenty-three cytologic criteria were used to evaluate the smears, and the results were scored and statistically analyzed. Reactive lesions consistently showed well-defined cell borders, normal nuclear/cytoplasmic (N/C) ratio, minimal or absent nuclear overlapping, round to oval nuclei with fine chromatin and prominent nucleoli. HGIL (adenocarcinoma in situ) showed feathered edges, rosettes, cell strips, increased N/C ratio, elongated nuclei, marked nuclear overlapping and nuclei with hyperchromatic, coarse chromatin. IA shared features with HGIL but had a greater tendency to show a dirty background, single cells, mitotic figures, nuclear pleomorphism and large nucleoli. Logistic regression studies indicated that the presence of mitotic figures, a dirty background and single cells increases the odds ratio for predicting invasion. LGIL showed features similar to those of high grade lesions, but the changes were more subtle. These lesions were also less cellular and less likely to show cell strips, feathered edges and rosettes. Similar to HGIL and IA, LGIL showed nuclear overlapping, increased N/C ratio, oval to elongated nuclei and nuclear hyperchromasia. There is overlap between the cytologic criteria for the various glandular lesions of the cervix. However, some of these criteria can consistently distinguish clinically significant lesions from reactive benign changes seen in the glandular epithelium.

The wide spectrum of biologic agents to which the lung may be exposed induces different responses in the lining epithelium and surrounding tissues. The resulting cytologic alterations can be specific in some cases, while in other circumstances the reaction may be nonspecific. A granulomatous response, as an example, can be induced by bacteria, fungi, spirochetes, or parasites. However, it can

The cytologic features of 84 ophthalmic lesions were evaluated using the squash technique at the time of frozen section. Of the 84 lesions, 55 were located in the orbit, 17 in the lacrimal gland, and 12 in the ocular adnexa. Lymphoid lesions comprised most of the cases (n = 47). In this group, 34 cases were malignant lymphomas and 13 were lymphoid hyperplasias. Inflammatory/granulomatous lesions and mesenchymal tumors comprised eight cases each. Epithelial neoplasms of the soft tissues of the orbit, lacrimal gland and eyelid constituted 12 cases, of which eight were malignant and four were benign. A total of nine cases were due to neurogenic tumors, neuroendocrine neoplasms, and melanocytic tumors. The squash technique provides a means to evaluate the architectural and cytologic details of ophthalmic lesions, without the intrinsic problem of frozen section artifact. We believe that the squash technique is a simple, quick, and useful method for the diagnosis of orbital/adnexal lesions.

Introduction Retroperitoneal mucinous cystadenomas are rare tumors. Only 25 cases have been reported in the English literature until 2002. The histogenesis is unclear, diagnosis is never made preoperatively and surgery is the only treatment. Case report We report an additional case.

A case of sacrococcygeal chordoma with anaplastic features is presented. The diagnosis of the anaplastic component was first established by fine needle aspiration (FNA) biopsy, which demonstrated the sarcomatous elements as well as the physaliferous cells characteristic of chordoma. Subsequent histologic examination confirmed these findings. While the FNA cytologic findings of chordoma have been previously reported, this is the first case of an anaplastic chordoma diagnosed by FNA biopsy. The embryologic origin of this unusual tumor and its differential diagnosis are discussed.

Diagnostic problems arise as a result of overlap of cytologic criteria of some squamous and glandular lesions of the female genital tract, lack of experience, or an overzealous attempt to interpret some features. This article emphasizes the role and limitations of cytology in the diagnosis of neoplasia and preneoplasia of squamous and glandular elements of the uterus. Sampling techniques greatly influence the pathologist's ability to interpret the material. The classifications and cytologic features of preneoplastic and neoplastic squamous and glandular epithelia, including the new Bethesda System for reporting, are reviewed. Problems in interpretation, particularly of nondysplastic conditions that mimic true neoplasia, and reasons for false-negative and false-positive results are discussed.

A wide variety of neoplasms and nonneoplastic cysts involves the ovary. Seventy-seven ovarian masses were aspirated using fine needles. They included 32 nonneoplastic cysts of various types, 29 celomic epithelial neoplasms, 10 germ cell neoplasms and 6 other neoplasms. The study was performed in order to elucidate the cytologic features of aspirates from these lesions and correlate them with the histologic features. Material aspirated from malignant neoplasms resulted in abundantly cellular specimens while aspirates from benign neoplasms and nonneoplastic cysts showed only scanty cells. Follicular cysts and corpus luteum cysts showed similar cell types but with various degrees of cellularity and incidence of cell types. Cysts lined by a single layer of cuboidal cells, such as paraovarian and paratubal cysts, were very similar cytologically. The three types of germ cell neoplasms encountered showed features which were diagnostic of each entity. It was difficult to discriminate betwee...

In this article, we discuss advances in our knowledge of the pathology of signet ring stromal cell tumor and related signet ring cell lesions of the ovary and a single case of signet ring stromal cell tumor of the testis. We divide ovarian signet ring cell lesions into 3 categories that reflect differences in their pathogenesis and histologic appearance. With 1 exception, all authentic cases of signet ring stromal cell tumor have been unilateral. Cases of ovarian signet ring stromal cell tumor from the literature can arise in 2 ways. The majority of cases arise multifocally from fibroma, whereas the remainder likely arise directly from the ovarian stroma. In difficult cases, immunocytochemistry provides improved diagnostic accuracy in distinguishing signet ring stromal cell tumor and its mimics from Krukenberg tumor. The most useful antibodies in this regard are epithelial membrane antigen and vimentin.

Gynecologic specimens are commonly submitted for intraoperative consultation, primarily to confirm the presence and histologic type of malignancy, as well as to determine the adequacy of resection by examining the surgical margins. To review and discuss the application, indications, contraindications, and limitations of intraoperative consultation regarding gynecologic specimens, as well as the causes of false-positive or false-negative frozen section results. Review of the pertinent literature and the authors' expertise and experience. In most instances, intraoperative consultation regarding gynecologic specimens accurately determines the type of malignancy, the status of the resection margins or the lymph nodes, and the extent and depth of involvement by a tumor. Although the pathologist and the surgeon must be aware of the limitations, the use of intraoperative consultation represents a highly sensitive and specific technique that can play a critical role in the management of...

Fine-needle aspiration has become an accepted and cost-effective procedure for rapid diagnosis of thyroid lesions. The routine use of fine-needle aspiration has reduced the rate of unnecessary surgery for thyroid nodules. To determine the accuracy of fine-needle aspiration biopsy diagnosis and to discuss the possible pitfalls. Design, Setting, and Participants.-Reports of 6226 fine-needle aspiration biopsies of the thyroid performed during a period of 16 years (1982-1998) were reviewed. Computerized reports of the fine-needle aspiration biopsies were sent to the physicians who performed the procedures, and clinical follow-up information regarding the patients was requested. Twenty-four clinicians participated in the study. Histologic diagnoses were available for 354 cases. The cytopathologic diagnoses were correlated with the histologic findings or clinical outcomes. The cytologic diagnoses were as follows: 210 (3.4%) malignant, 450 (7.2%) suspicious, 3731 (60%) benign, and 1845 (29...

We report the histopathologic features of the knee bone and synovium and the cytologic features of the synovial fluid from a patient with alpha-mannosidosis. The synovium showed marked papillary hyperplasia with infiltration of foamy histiocytes containing periodic acid-Schiff-positive, diastase-resistant material. Severe degenerative changes were seen in the knee bone. The synovial fluid showed increased numbers of macrophages containing periodic acid-Schiff-positive, diastase-resistant material. The differential diagnostic considerations in the synovial fluid are also discussed.

We used exchange saturation analysis at 15 degrees to quantitate total cytoplasmic and nuclear androgen receptor content of 70 patient specimens. Cytoplasmic androgen receptor contents (fmol/mg DNA) for eight specimens of clinically benign hyperplasia, 14 specimens of histologically hyperplastic prostate obtained at cystoprostatectomy, and carcinomatous and noncarcinomatous prostate obtained at radical prostatectomy for prostatic carcinoma, 48 specimens, respectively, were 830 +/- 165 (mean +/- S.E.), 890 +/- 445, 955 +/- 240, and 750 +/- 95. Nuclear androgen receptor contents of these same specimens, respectively, were 275 +/- 40, 235 +/- 30, 345 +/- 25, and 350 +/- 30; whereas, the values of the cytoplasmic/nuclear receptor content, respectively, were 3.25 +/- 0.55, 3.05 +/- 0.80, 2.50 +/- 0.50, and 2.80 +/- 0.40. Multiway analyses of variance of these cross-sectional data showed that there was no significant difference (p greater than 0.05) between group mean values. This result ...

A total of 464 fine-needle aspiration biopsy specimens in 450 patients was studied. The majority of these aspirates were performed by the pathologist. The technic was 95% sensitive, 99.5% specific, and 97.0% accurate when correlated with histopathology or long-term follow-up. The complication rate was 0.9% and occurred only when needles larger than #22 were used to aspirate lung lesions resulting in pneumothorax. A flow chart for the role of needle biopsy in investigating masses of various organs is presented, together with some illustrative examples. In the current atmosphere of cost-containment, this inexpensive yet fast and accurate technic should play an important role in surgical decision making. However, pathologists and clinicians should be aware of the limitations and should not hesitate in obtaining an open biopsy when necessary, particularly when clinical suspicion for malignancy is not confirmed by the aspiration, in view of the small but significant (4.9%) false-negative...

Fluid aspirated from a subarachnoid cystic lesion that covered and compressed part of the left frontal lobe was examined cytologically and compared with histologic sections of the cyst wall. The fluid contained epithelial and histiocytelike cell populations. The epithelial cells were tall columnar, occurring singly or in clusters or sheets. Many cells were ciliated and their cytoplasm showed characteristic refractile granules. The differential diagnosis of this rare type of subarachnoid cyst and the mechanism of the development are discussed. Cytologic evaluation of the fluid of the subarachnoid cysts is potentially a more accurate method of classification of these lesions than is random biopsy of the cyst wall. It is of particular importance in cases with a history of growth, in which the progressive expansion results in attenuation of the diagnostic epithelial lining of the cyst.

Adenomatoid hyperplasia of minor salivary glands is an idiopathic lesion usually involving the palate and mimicking a primary salivary gland neoplasm. In particular, the lesions may resemble low-grade mucoepidermoid tumors clinically and by fine needle aspiration (FNA) cytology. An illustrative case is presented, and the nature of this unusual entity is reviewed. Its importance in the differential diagnosis of FNA biopsies of minor salivary gland lesions is also discussed.

To clarify the use of cytologic preparations, particularly those previously stained by the Papanicolaou method, for the immunocytochemical evaluation of large-cell carcinomas (LCCs), 37 cytologic preparations from cases diagnosed as LCC were examined using a battery of immunocytochemical stains for keratin, chromogranin, common leukocyte antigen (CLA) and B72.3. Thirty-two specimens were from the thoracopulmonary region (12 fine needle aspirates of the lung, 7 bronchial brushings, 5 bronchial washings, 2 sputa and 6 pleural fluids); the remaining specimens were fine needle aspirates of 3 lymph nodes, 1 vertebral body and 1 liver. Of the specimens analyzed, 30 of 37 were positive for keratin and 7 of 35 were positive for B72.3 (6 were positive for both). Only 1 of 37 was positive for CLA while none of 37 was positive for chromogranin. Six specimens showed no reaction with either keratin, B72.3 or chromogranin. These results confirm that the majority of LCCs consist of epithelial cell...

Fine needle aspiration biopsy of bone lesions is routinely used in the metastatic workup of patients with radiographically suspicious areas. However, caution must be used when interpreting smears from aspirates performed on primary bone neoplasms. These tumors are often heterogeneous, and problems with sampling may be encountered. We report a case of a 25-year-old male who presented with a 3-cm lytic lesion in the tibia. A diagnosis of benign fibroosseous lesion was based on the clinical presentation, radiographic appearance and presence of numerous sheets and single cytologically bland spindle cells. Subsequent curettage of the specimen revealed an adamantinoma with a prominent fibrous component. Most of these rare, locally aggressive neoplasms are located in the tibia. They are characterized histologically as having a fibrous background with islands of basaloid, spindle or squamoid cells. Furthermore, a differentiated, regressing variant with an osteofibrous dysplasia-like appeara...

Pancreatic cystic epithelial neoplasms present diagnostic challenges in cytology. An accurate diagnosis is important since the prognosis and treatment may vary. We report the cytologic features in fine needle aspirates of four cases of cystic neoplasms of the pancreas (two micro-cystic adenomas, one mucinous cystic neoplasm and one mucinous cystadenocarcinoma). Smears were evaluated as to their cellularity, content and predominant cell type. Aspirates from the microcystic adenomas yielded hypocellular material with rare strips of cuboidal cells having bland nuclei and pale cytoplasm. No mucinous material was identified in the background, but the cells stained positively with periodic acid-Schiff stain. Smears from the mucinous cystic neoplasm were moderately cellular and contained abundant mucinous material. The columnar epithelial cells were arranged in tight sheets, clusters and strips. Most cells had benign nuclear features with focal mild nuclear atypia. Key cytologic findings n...

A histologic study of 15 ovaries from patients in whom endometrial adenocarcinoma developed before the age of 40 years was performed. These ovaries were randomized with control groups of 21 age-matched normal ovaries and 25 ovaries from patients who had Stein-Leventhal syndrome. The study was done in an attempt to determine whether the ovaries from these young patients showed any histologic feature that would indicate abnormal ovarian function resulting in unopposed estrogenic stimulation of the endometrium. Histologic features assessed included type and size of cysts, presence and number of primary follicles, corpora lutea, corpora albicantia, and presence of stromal luteinization and sclerosis. Analysis of the results indicated that from a histologic point of view ovaries of patients less than 40 years old who have endometrial adenocarcinoma are more similar to normal ovaries than to polycystic ovaries. Only 11.1% of ovaries of the study group had features suggestive of polycystic...

A cross sectional retrospective study of 400 cases of amniocentesis was performed to evaluate the reliability of using fetal fat staining cells as a method for assessment of fetal age and maturity. A sharp rise in the percentage of these cells in amniotic fluid occurred after 37 weeks of gestation and a level of 20 per cent or more indicated fetal age of 38 weeks or more, corresponding to maturity by our definition. The false positive and negative rates were 3.5 per cent and 14 per cent respectively. The pre-eclamptics, diabetics and Rh sensitized groups fell within the distribution of the normal population. The dysmature group, however, showed an earlier rise (20% at 36 weeks). The origin of the fetal fat staining cells and the reasons for the early rise in dysmaturity are discussed. Estimation of fetal fat staining cells in the amniotic fluids using the 20 per cent level is a reliable test for maturity in normal and some abnormal pregnancies, excluding dysmaturity.

To determine the role of cytology in differentiating serous surface carcinoma of the peritoneum (SSCP) from other morphologically similar tumors, including ovarian carcinoma and other peritoneal lesions, and to define the value of cytology in the follow-up of patients with SSCP. Twenty-one ascitic fluids and seven peritoneal washings obtained from 19 patients with histologically confirmed SSCP were reviewed and their cytologic features tabulated and analyzed. Eighteen of the specimens were from initial diagnostic paracenteses or exploratory laparotomies. These showed mostly three-dimensional tumor cell clusters, as well as single malignant cells, with occasional papillae. The cytoplasm was abundant and often vacuolated. The cytomorphologic features of SSCP enabled differentiation from other conditions involving the peritoneal surface, including mesothelial hyperplasia, malignant mesothelioma, endometriosis and endosalpingiosis. However, there were no characteristic features that dif...

Osteomyelitis due to Cryptococcus neoformans typically exhibits lytic lesions on radiographs. Extensive periosteal reaction is an uncommon feature. A 68-year-old man presented with pain and swelling in the left elbow. Radiologic studies exhibited a lytic humeral lesion with extensive periosteal reaction, interpreted as a malignant neoplasm. Fine needle aspiration biopsy (FNA) revealed abundant cryptococcal organisms. Cryptococcus is an uncommon cause of lytic osseous lesions that may mimic malignant neoplasms. Extensive periosteal reaction may support a radiologic diagnosis of primary osseous malignancy in rare cases. FNA with examination of Diff-Quik-stained slides may be employed for distinguishing cryptococcal osteomyelitis from malignant tumors and for prompt identification of the organisms.