The Reemergence of Measles.

OBJECTIVES: Present-day pathologists may be unfamiliar with the histopathologic features of measles, which is a reemerging disease. Awareness of these features may enable early diagnosis of measles in unsuspected cases, including those with an atypical presentation. Using archived tissue samples from historic patients, a unique source of histopathologic information about measles and other reemerging infectious diseases, we performed a comprehensive analysis of the histopathologic features of measles seen in commonly infected tissues during prodrome, active, and late phases of the disease. METHODS: Subspecialty pathologists analyzed H&E-stained slides of specimens from 89 patients accessioned from 1919 to 1998 and correlated the histopathologic findings with clinical data. RESULTS: Measles caused acute and chronic histopathologic changes, especially in the respiratory, lymphoid (including appendix and tonsils), and central nervous systems. Bacterial infections in lung and other organs contributed significantly to adverse outcomes, especially in immunocompromised patients. CONCLUSIONS: Certain histopathologic features, especially Warthin-Finkeldey cells and multinucleated giant cells without inclusions, allow pathologists to diagnose or suggest the diagnosis of measles in unsuspected cases.

Mucinous Neoplasms of the Ovary: Radiologic-Pathologic Correlation.

Mucinous neoplasms of the ovary account for 10%-15% of ovarian neoplasms. They may be benign, borderline, or malignant. The large majority are benign or borderline, accounting for 80% and 16%-17%, respectively. Mucinous neoplasms of the ovary most commonly affect women in their 20s to 40s. The clinical manifestation is nonspecific, but most mucinous ovarian neoplasms manifest as large unilateral pelvic masses. At gross pathologic analysis, mucinous ovarian neoplasms appear as large multiloculated cystic masses. The contents of the cyst loculi vary on the basis of differences in internal mucin content. At histologic analysis, mucinous ovarian neoplasms are composed of multiple cysts lined by mucinous epithelium, often resembling gastrointestinal-type epithelium. Imaging evaluation most commonly includes US and/or MRI. The imaging findings parallel the gross pathologic features and include a large, unilateral, multiloculated cystic mass. The cyst loculi vary in echogenicity, attenuation, and signal intensity depending on the mucin content. Mucinous neoplasms of the ovary are staged surgically using the FIGO (International Federation of Gynecology and Obstetrics) staging system. Primary treatment is surgical, with adjuvant chemotherapy considered in the uncommon case of mucinous carcinoma with extraovarian disease. Since most mucinous ovarian neoplasms are benign or borderline, the overall prognosis is excellent.

From the radiologic pathology archives: diseases of the male breast: radiologic-pathologic correlation.

Male breast disease includes a variety of benign and malignant conditions, many of which are hormonally influenced. Gynecomastia and skin lesions account for the majority of conditions in symptomatic men with a palpable abnormality, and these conditions should be accurately recognized. Imaging patterns of gynecomastia include nodular, dendritic, and diffuse patterns. Histopathologically, the nodular and dendritic patterns correlate with the florid and quiescent (fibrotic) phases of gynecomastia, respectively. The diffuse pattern may have features of both phases and is associated with exposure to exogenous estrogen. Benign-appearing palpable masses in male patients should be approached cautiously, given the overlapping morphologic features of benign and malignant tumors. In addition to gynecomastia, other benign male breast tumors include lipoma, pseudoangiomatous stromal hyperplasia, granular cell tumor, fibromatosis, myofibroblastoma, schwannoma, and hemangioma. Male breast cancer accounts for 1% of all breast carcinomas. Invasive ductal carcinoma accounts for the majority of cases in adult males and typically appears as a subareolar mass without calcifications that is eccentric to the nipple. Other epithelial and mesenchymal tumors that may occur, albeit not as commonly as in women, include papillary carcinoma, invasive lobular carcinoma, adenoid cystic carcinoma, liposarcoma, dermatofibrosarcoma, pleomorphic hyalinizing angiectatic tumor, basal cell carcinoma of the nipple, hematopoietic malignancies, and secondary tumors. Knowledge of the natural history, clinical characteristics, and imaging features of tumors that occur in the male breast will help narrow the radiologic differential diagnosis and optimize treatment.

Distribution of HPV genotypes in 282 women with cervical lesions: evidence for three categories of intraepithelial lesions based on morphology and HPV type.

Previously we found differences in the distribution of the individual human papillomavirus types in cervical cancers and high-grade squamous intraepithelial lesions. This suggested that there were differences in risk for progression of high-grade squamous intraepithelial lesions that were related to human papillomavirus type within the category of oncogenic genotypes. In this work, we add additional cases including low-grade squamous intraepithelial lesions. ThinPrep samples from 282 squamous intraepithelial lesions and invasive cervical cancers were categorized morphologically by consensus interpretation and genotyped for 27 individual human papillomavirus types by polymerase chain reaction-based reverse line blot analysis using PGMY09/PGMY11 consensus primers for the L1 open reading frame. The 27 human papillomavirus types were divided into three categories: high risk 16, 18, 31, 45; intermediate risk 33, 35, 39, 51, 52, 56, 58, 59, 68, 73, 82, 83; and low risk: 6, 11, 26, 40, 42, 53, 54, 55, 57, 66, and 84. Of the 282 cases of cancer and squamous intraepithelial lesions, 95.7% were positive for one or more of 27 human papillomavirus types and 38.7% had two or more genotypes. Three major categories of squamous intraepithelial lesions were identified based upon the combination of consensus diagnosis and human papillomavirus category: (1) high-grade squamous intraepithelial lesions associated with high-risk human papillomavirus types that appear to be at increased risk for progression to carcinoma; (2) squamous intraepithelial lesions (typically low-grade intraepithelial lesions and high-grade lesions consistent with moderate dysplasia) associated with intermediate risk human papillomavirus types with limited or indeterminate risk for progression; (3) low-grade squamous intraepithelial lesions associated with low-risk human papillomavirus types with little or no risk for progression. Only a subset of human papillomavirus genotypes commonly considered to be oncogenic were closely associated with invasive cervical cancer and high-grade squamous intraepithelial lesions classed as severe dysplasia. Other oncogenic types were closely associated with high-grade squamous intraepithelial lesions of moderate dysplasia and low-grade squamous intraepithelial lesions. This suggests that risk for progression to invasion in squamous intraepithelial lesions is closely related to human papillomavirus genotype. Knowledge of the associated human papillomavirus type in women with morphologic squamous intraepithelial lesions may help to clarify risk for progression.

Mammary ducts with and without focal myoepithelial cell layer disruptions show a different frequency of white blood cell infiltration and growth pattern: implications for tumor progression and invasion.

The authors' previous studies revealed that a subset of ductal carcinoma in situ (DCIS) contained focally disrupted myoepithelial (ME) cell layers and basement membrane (BM). As the disruption of these two structures is a prerequisite for tumor invasion, and white blood cells (WBCs) contain digestive enzymes capable of degrading both the BM and damaged host cells, this study was designed to assess the possible roles of WBC in ME cell layer disruptions and tumor invasion. A total of 23 DCIS containing ducts with focally disrupted ME cell layers were selected from 94 such cases identified in the authors' previous studies. Two consecutive sections from each case were double immunostained, one with leukocyte common antigen (LCA) plus smooth muscle actin (SMA) and the other with Ki-67 plus SMA. Ducts lined by at least 50 epithelial cells and distinct ME cell layers were examined. A total of 191 duct cross-sections were found to contain focal ME cell layer disruptions; of these, 186 (97.4%) were with and 5 (2.6%) were without WBC infiltration. Of 207 morphologically similar sections without ME disruptions, 46 (22.2%) were with and 161 (77.8%) were without WBC infiltration. Ki-67-positive cells in ducts with focally disrupted ME cell layers were generally subjacent to ME cell layers, and more than 30 clusters of multiple proliferating cells were seen directly overlying or near focally disrupted ME cell layers. In contrast, Ki-67-positive cells in ducts without ME disruptions were scattered over the entire epithelial compartment. The significantly different frequency of WBC infiltration and clusters of multiple proliferating cells in ducts with and without ME disruptions suggests that WBCs might play important roles in ME disruption and tumor invasion.

Comparison of human papillomavirus genotypes in high-grade squamous intraepithelial lesions and invasive cervical carcinoma: evidence for differences in biologic potential of precursor lesions.

High-grade squamous intraepithelial lesions of the cervix are heterogeneous in their invasive potential. Comparison of human papillomavirus types between invasive cervical carcinoma and high-grade squamous dysplasia may provide insight into this biological variability. Liquid-based Pap specimens from 55 high-grade intraepithelial lesions and 47 invasive cervical carcinomas were analyzed by reverse line blot for 27 human papillomavirus types designated high, intermediate, or low risk. Human papillomavirus DNA was present in all high-grade intraepithelial lesions (23 different types) and in 94% (13 types) of invasive carcinomas. High-risk types were present in 81% of invasive carcinomas compared to 58% of high-grade intraepithelial lesions. Severe dysplasias harbored more (79%) high-risk human papillomaviruses as compared to moderate dysplasias (37%). In 40% of high-grade dysplasia cases (59% of moderate dysplasias; 21% of severe) and 13% of invasive carcinomas, intermediate-risk genotypes were identified in the absence of high-risk HPV types. Human papillomavirus 16 was the most common type in all categories, including 47% of high-grade squamous dysplasias (26% moderate; 68% severe) and 61% of invasive carcinomas. Both high-risk type (P=0.0004) and type 16 (P=0.0007) human papillomaviruses were positively associated with increasing severity of diagnosis. The heterogeneous nature of high-grade squamous dysplasias as compared to invasive carcinoma is evident by the wider spectrum of associated human papillomavirus types. Likewise, moderate dysplasia appears to be more heterogeneous in viral type than severe dysplasia. Moderate cases were more often associated with intermediate-risk types, while high-risk types were more prevalent in severe dysplasias and invasive cancers. Moderate dysplasia cases harboring viral types infrequently found in cancers may have a low risk for progression. Human papillomavirus genotyping of high-grade squamous intraepithelial lesions may be important in assessing risk for progression to invasion.

Utilization of polymerase chain reaction on archival cytologic material: a comparison with fresh material with special emphasis on cerebrospinal fluids.

Use of the polymerase chain reaction (PCR) for the detection of B- and T-cell clonality, Epstein-Barr virus (EBV) and Human Herpes Virus 8 (HHV 8) infection is gaining increasing importance as a diagnostic modality. These tests are usually performed on fresh specimens. There are instances when fresh material is not available and there is a clinical utility for the performance of PCR on archival material via slide scrape lysates (SSL). However, the suitability of archival material may be questioned. Records were searched for all archival cytology cases submitted for SSL molecular diagnostics tests since 1998. Results for each case were analyzed for PCR amplification status and individual test results. A randomly chosen control group of equivalent cytologic samples submitted fresh was evaluated for comparison of amplification status. In all, 241 PCR runs were performed on SSL of archival material from 112 cytologic samples (89 cerebrospinal fluids (CSFs), 13 fine-needle aspirates (FNAs), 10 effusions). Out of these samples, 95 (85%) had amplifiable DNA, as assessed by a positive reaction for glyceraldehyde phosphate dehydrogenase (GAPDH). For the control group, 320 PCR runs were performed on 112 fresh cytologic samples (89 CSFs, 13 FNAs, 10 effusions). In total, 102 samples (91%) had amplifiable DNA. There was no statistical difference in the amplification yield between the two groups (P = 0.2177). A morphologic review of 16 of the 17 SSL archival cytologic cases that did not show amplification revealed 11/16 to be of sparse cellularity. Molecular diagnostic tests are performed routinely on fresh cytologic samples with excellent results. At times critical decisions on patient care may need to be made when fresh tissue is not available for molecular diagnostic tests. SSL of archival cytologic material can be used with excellent results for molecular diagnostic tests when fresh material is not available or when the cytologic diagnosis needs further clarification.

Extended peripheral zone biopsy schemes increase cancer detection rates and minimize variance in prostate specific antigen and age related cancer rates: results of a community multi-practice study.

PURPOSE: We assessed the impact of age and prostate specific antigen (PSA) on extended systematic biopsy schemes for detecting prostate carcinoma and better characterized these tumors as a function of patient age and PSA. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,299 consecutive patients who underwent initial systematic biopsy performed by 167 community based urologists. A total of 12 systematic biopsies of the peripheral zone were obtained in all patients. Various biopsy schemes were then created and cancer detection rates were calculated. Data analyses were stratified by patient age and PSA. RESULTS: On biopsy 1,020 patients (44.4%) had cancer. Detection rates increased with increasing patient age. Increasing age and PSA were associated with larger, higher grade tumors. Overall and unique site specific cancer detection rates were highest for laterally directed biopsies and the apical biopsy of the standard sextant scheme. The 12 site biopsy scheme outperformed all other schemes in patients with PSA 7 ng./ml. or less and in those 60 years or younger. The variation in age related and PSA related detection rates was greatest for the standard sextant scheme and this variability decreased for extended biopsy schemes. CONCLUSIONS: This multi-practice community based study confirms the inadequacy of sextant biopsies and emphasizes the need for extended peripheral zone sampling of the lateral aspect of the prostate. Generally increasing patient age and PSA were associated with larger, higher grade tumors. Extended biopsy schemes minimize PSA and age related detection rates.