Stephen S. Raab

Detection of estrogen receptor by immunohistochemistry in pulmonary adenocarcinoma

BACKGROUNDnThe distinction between primary adenocarcinoma and metastatic breast carcinoma in the lung is important for therapeutic purposes. There is a good deal of morphologic overlap between primary pulmonary adenocarcinoma and breast carcinoma metastatic in the lung. Many diagnosticians rely upon the presence of estrogen receptor (ER) in tumors of the lung in women in order to make a pathologic diagnosis of metastatic breast carcinoma. There are conflicting data in the literature regarding the presence of ER in lung carcinomas. In this study, we examined primary lung adenocarcinomas with monoclonal antibodies to two different clones to ER (clone 6F11 and clone 1D5), and progesterone receptor by the immunoperoxidase method in order to ascertain if ER is detectable in primary lung adenocarcinomas.nnnMETHODSnTwenty-five resected solitary pulmonary nonmucinous bronchioalveolar carcinomas (15 female, 10 male) and 20 resected solitary pulmonary adenocarcinomas of no special type (12F, 8 mol/L) were studied by the immunohistochemical method using heat-induced epitope retrieval. Immunostaining was semiquantitated, and positive results included nuclear staining for ER and progesterone receptor. All of these tumors were documented as primary pulmonary adenocarcinomas clinically and pathologically.nnnRESULTSnNuclear ER was seen only with the 6F11 clone, in 56% of the bronchioalveolar type and 80% of the no special type. No nuclear ER was seen in carcinomas utilizing the 1D5 clone. There was no progesterone receptor detectable in carcinomas.nnnCONCLUSIONSnEstrogen receptor is present in the majority of lung adenocarcinomas, and detection of ER in lung adenocarcinomas is dependent upon the antibody clone that is used. Epitope recognition may account for the differences in immunoreactivity between these two antibodies, although a cross-reactive antibody reaction cannot be completely excluded. Further study is warranted to discern the nature of the 6F11 clone immunoreactivity with nuclei of lung adenocarcinomas. The clinical significance and ramifications of ER in pulmonary adenocarcinomas remain unknown. Caution should be exercised by clinicians and pathologists in accepting a diagnosis of metastatic breast carcinoma in lung based on the presence of ER detected by clone 6F11.

Cytology of angiosarcoma : Findings in fourteen fine-needle aspiration biopsy specimens and one pleural fluid specimen

We report the cytologic features of 15 cases of angiosarcoma from various sites and include 14 fine-needle aspiration (FNA) biopsy specimens and 1 pleural fluid specimen. Six were initial diagnoses with histologic confirmation; an additional case in the liver was an initial diagnosis without tissue confirmation. One case represented lymph node metastasis from a primary prostatic epithelioid angiosarcoma. In 10 cases, immunohistochemical staining for factor VIII-related antigen, CD34, CD31, or Ulex europaeus agglutinin I was performed on the cytology or histology specimen. The aspirates varied in cellularity, and the degree of nuclear atypia ranged from relatively bland in a case of low-grade angiosarcoma of the prostate to highly pleomorphic in a lymph node metastasis from a facial cutaneous angiosarcoma. Vasoformative features such as intracellular RBCs, well-formed vessels, attempts at microacinar/lumen formation, and intracytoplasmic lumens were variably present. The background was bloody in all specimens, with necrosis in rare cases. This cytologic series emphasizes that the cytologic features are heterogeneous but that the diagnosis can be suggested by fine-needle aspiration (FNA) when vasoformative features are present. The diagnosis can be made conclusively by FNA with immunocytochemical confirmation of endothelial differentiation.

The role of fine-needle aspiration cytology in the evaluation of metastatic clear cell tumors

Clear cell tumors (CCTs) occur as primary neoplasms in a number of anatomic sites. Due to their overlapping morphologic features, these tumors can be challenging for the cytologist, particularly when they present as metastatic lesions.

Cytohistologic discrepancies: a means to improve pathology practice and patient outcomes.

The use of cytohistologic discrepancies to investigate and reduce error seldom is studied. All gynecologic discrepancies (n = 283; 0.87% and 7.37% of all cytologic and histologic cases, respectively) and nongynecologic discrepancies (n = 146; 2.26% and 0.44% of all cytologic and histologic cases, respectively) for 26 months were classified as sampling or interpretive. Specimen type and pathologist discrepancy percentages, effect of discrepancies on patient outcome, and interobserver agreement of discrepancies were evaluated. Discrepancies were interpretive in 67% and 34% of gynecologic and nongynecologic cases, respectively. Statistically significant associations were seen between individual pathologist and discrepancy percentages. Breast (1.2%) and bronchial (0.8%) cytologic diagnoses had the highest discrepancy percentages. The kappa scores ranged from 0.02 to 0.45 for pairwise agreement of discrepant cases. Of nongynecologic interpretive discrepancies available for review, 63% (27/43) and 14% (6/43) were of no or minor clinical significance, respectively. Cytohistologic correlation is a useful tool to monitor performance and to identify specimen types prone to error.

Fine‐needle aspiration for the diagnosis of orbital hematolymphoid lesions

Ocular and periocular hematolymphoid diseases are a diverse group of lesions affecting various soft tissue structures within the orbital cavity. Lymphoid proliferations in particular are among the most commonly diagnosed entities in orbital pathology. When noninvasive techniques fail to confirm or rule out the suspicion of orbital neoplasia, fine‐needle aspiration (FNA) may be of use in establishing a diagnosis in a reliable, timely, cost‐effective and safe manner. From 1986 to 1999, 79 orbital/ocular needle aspiration biopsies were conducted by staff ophthalmologists at Allegheny General Hospital. Slides from these cases and corresponding reports were pulled from the cytology files and grouped into the two broad categories of hematolymphoid and other. Specimens came from patients ranging in age from 14 to 88 years (mean, 64 years) with eight patients having known histories of hematolymphoid disorders. Immunocytochemical (ICC) studies were performed in 33% of the cases (14/43). Review of the diagnoses for the 79 aspiration specimens revealed 30 cases diagnosed as lymphoma/atypical lymphocytic infiltrate, cases diagnosed as inflammation or abscess, three cases diagnosed as plasmacytoma, three cases called suboptimal with scant inflammatory cells, and one case of Langerhans cell histiocytosis. Hematolymphoid diagnoses accounted for 54% (43/79) of all diagnoses. Histologic correlation was available in 33% (14/43) of the cases (nine cases diagnosed as cytologically atypical/malignant and five cases called cytologically benign/suboptimal) with 100% correlation. Hematolymphoid lesions of the orbit are readily diagnosed by FNA. Because many hematolymphoid malignancies are treated as systemic or multiorgan system diseases and because ocular lymphomas may also involve the central nervous system, nonsurgical attempts at diagnosis have the potential to spare the patient procedural morbidity which may be associated with open biopsy. Our experience indicates that the combination of FNA, judicious use of immunocytochemical studies, and correlation with pertinent clinical information and imaging studies allows for reliable and effective classification and diagnosis of orbital hematolymphoid lesions. Diagn. Cytopathol. 2000;23:314–317.

Can glandular lesions be diagnosed in pap smear cytology

Many reports have been published on the accuracy of the cervical vaginal smear for squamous lesions, and the literature contains fewer reports on the accuracy of the cervical vaginal smear for glandular lesions. The sensitivity of glandular lesion diagnosis depends on the subtype of lesion. The diagnostic sensitivity is highest for invasive endocervical adenocarcinoma and lowest for endometrial adenocarcinoma. The ability of some of the Bethesda system categories for glandular lesions to describe what they purport to describe is questionable. The Bethesda system categories of adenocarcinoma accurately classify adenocarcinomas. The Bethesda System category of atypical glandular cells of undetermined significance (AGUS) is a misnomer. Although many cases of adenocarcinoma in‐situ are placed in this category, follow‐up of patients with AGUS show that the majority of patients with clinically significant lesions have squamous dysplasias. Other categories of AGUS, such as AGUS favor endometrial origin, are more appropriately named and encompass endometrial lesions which are either neoplastic or non‐neoplastic. Diagn. Cytopathol. 23:127–133, 2000.

p53 protein overexpression in smooth muscle tumors of the uterus

p53 is a nuclear phosphoprotein whose overexpression may portend a poor prognosis in a variety of neoplasms. In this immunohistochemical study we examined p53 overexpression in a variety of uterine smooth muscle tumors (34 leiomyosarcomas, 18 leiomyomas, and six smooth muscle tumors of uncertain malignant potential [STUMPs]). p53 immunoreactivity was observed in none of 18 (0%) leiomyomas, one of six (17%) STUMPs, and 16 of 34 (47%) leiomyosarcomas. Reactivity was not observed in the surrounding nonneoplastic uterine smooth muscle. Strong p53 overexpression in the leiomyosarcomas was significantly associated with high grade morphology (P = .013) and a high stage at the time of presentation (P = .021). In 25 leiomyosarcoma patients with clinical follow-up, p53 overexpression was associated with shorter length of survival (P = 0.024). However, this effect was not independent of tumor stage or grade. A regression analysis showed that tumor stage was the only independent predictor of length of survival. Our study size is small, and further studies are warranted to determine the significance and replicability of these findings.

Fine-needle aspiration for the diagnosis of primary epithelial tumors of the lacrimal gland and ocular adnexa.

Results of fine‐needle aspiration (FNA) of solid‐tissue neoplasms arising in the periocular glands are infrequently reported in the literature. To our knowledge, no previous series relating to this topic exist. Neoplastic processes that arise in the semiconfined area of the orbit behave as space‐occupying lesions. Such lesions can exert significant pressure on the globe, be responsible for altered vision, and result in proptosis. When noninvasive techniques fail to confirm or rule out the suspicion of a neoplastic lacrimal or adnexal lesion, FNA may be of use in establishing a diagnosis in an efficient, reliable, timely, cost‐effective, and safe manner. During the 14‐yr interval from 1986–1999, 77 orbital/ocular needle aspiration biopsies were conducted by staff ophthalmologists at Allegheny General Hospital (Pittsburgh, PA). Review of the diagnoses for these specimens revealed seven primary solid‐tissue lesions of the lacrimal gland and other adnexal glands, all arising in adult patients (age range, 45–92 yr; mean age, 74 yr). Primary lacrimal and adnexal gland neoplasms were found to represent ∼9% of orbital fine‐needle aspirations (7/79). The 7 cases included 3 lacrimal gland lesions diagnosed as benign mixed tumors, 3 lesions diagnosed as adenoid cystic carcinoma of the lacrimal gland, and 1 tumor diagnosed as sebaceous carcinoma of the meibomian holocrine glands. Cytologic diagnoses were rendered using standard criteria for salivary gland‐type tumors. Tissue confirmation was available from surgical follow‐up in 4 of the 7 cases, with 100% correlation. Although primary neoplasms of the lacrimal gland and glands of the eyelids are rare, accurate diagnoses of such lesions may be established with minimally invasive aspiration techniques. Preoperative aspiration biopsy diagnoses provide a great advantage to ophthalmic surgeons who routinely operate in a conservative fashion in an area of the body requiring great attention to cosmesis. Our experience indicates that FNA is a reliable and effective tool in the diagnosis and management of primary lacrimal and ocular adnexal tumors. Diagn. Cytopathol. 24:86–89, 2001.

De novo establishment and cost-effectiveness of Papanicolaou cytology screening services in the socialist Republic of Vietnam

BACKGROUNDnCervical carcinoma is the leading cause of cancer-related death among women in the developing world. The absence of cervical screening in Vietnam and other developing countries is due in large part to the perceived expense of implementing Papanicolaou cytology screening services, although, to the authors knowledge, the cost-effectiveness of establishing such services has never been studied in a developing country.nnnMETHODSnUsing decision analytic methods, the authors assessed cost-effectiveness of Pap screening from a societal perspective in Vietnam, the worlds 9th most populous developing country (estimated 1999 population, 79 million). Outcomes measured included life expectancy, cervical carcinoma incidence, cost per woman, and cost-effectiveness.nnnRESULTSnTotal costs to establish a nationwide 5-year interval Pap screening program in Vietnam will average less than

Microtubule-Associated Protein-2: A New Sensitive and Specific Marker for Pulmonary Carcinoid Tumor and Small Cell Carcinoma

148,400 annually during the 10-year time period assumed necessary to develop the program and may be considerably lower if only high risk geographic areas are targeted. Maintenance costs will average less than