High-risk human papillomavirus (HR-HPV) is recognized as the primary cause for the development of cervical cancers and their precursor lesions. We investigated whether high-grade cervical dysplasia correlates with high viral load of HR-HPV in an age-dependent manner. Cases were retrospectively selected to include patients with a prior cytological diagnosis of ASCUS or higher grade squamous intraepithelial lesions, and a positive Digene Hybrid Capture II (HC-II) HR-HPV testing within 2 months before or after cervical biopsy. The quantitative viral load data was classified as negative, low, moderate and high according to the manufacturer's instruction. Cases were then stratified into 4 age groups: <= 22 years, 23-30 years, 31-40 years and >40 years. Chi-Square analysis and logistic regression were performed where appropriate. A total of 995 patients were identified. Age categories were significantly associated with HPV loads (p= 0.046). Moderate to high viral loads of HPV were significantly related to the histological grade of dysplasia (p= 0.029). Logistic regression analysis further confirmed the association of HPV with histological grades, even after adjusting for age factor. In particular, highgrade dysplasia (p= 0.011) but not low grade dysplasia (p= 0.140) was significantly associated with moderate to high HPV loads. Patients of 22 years old or younger were the only group found significantly correlated with high viral loads of HPV (p= 0.015). In conclusion, high-grade squamous intraepithelial lesions and patients' age of 22 years old or younger are significantly associated with a moderate to high viral load of HR-HPV.

Ovarian primary carcinoid tumors of pure histological type can pose a significant diagnostic challenge in its separation from metastatic carcinoids from the gastrointestinal tract. Yet, their clinical management and prognosis are drastically different. At the molecular level, ovarian primary carcinoid tumors are thought to be of germ cell origin, frequently after the first meiotic division. We report a 21.5-cm ovarian insular carcinoid tumor in a 50-year-old woman who had no evidence of extraovarian tumor. The absence of teratomatous components and the presence of lymphovascular invasion prompted additional studies to rule out a metastatic tumor. The nature of this primary ovarian tumor was eventually confirmed by demonstration of its germ cell origin through DNA genotyping.

To the Editor.—We read with great interest the article by Folpe and Cooper in the October 2007 issue of the Archives of Pathology & Laboratory Medicine1 and agree with the diagnostic approach and immunohistochemistry panel proposed by the authors. Regarding squamous cell carcinomas, Sigel et al2 reported that only 69% of spindle cell squamous cell carcinomas expressed CK5/6. We recently published a series3 of 13 cases of cutaneous spindle cell squamous cell carcinomas, in which all the tumors revealed diffuse positivity for p63. Our study suggests that p63 is a useful adjunct immunostain and has the advantage of being a nuclear marker, which allows easier and more definitive interpretation.

Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States, most frequently presenting in postmenopausal women. Two major subtypes of endometrial adenocarcinoma are now well recognized. The more common (type 1) has an endometrioid morphology with several variants. The far more aggressive subtype (type II) that accounts for only 10% of cases more frequently displays a serous morphology, but may have pure clear cell differentiation. We present here an interesting aspect of the type II carcinoma manifested in a case we recently received for consultation at the Department of Pathology, Yale New Haven Hospital. Seven slides were available for review from a 67-year-old woman, who had undergone a total hysterectomy and bilateral salpingo-oophorectomy. An endometrial polyp (Figure 1) was the major finding. Within the polyp, a high-grade malignant serous epithelium focally replaced the surface epithelium and superficial glands of the endometrial polyp (Figure 2). Despite the absence of any myometrial invasion, endocervical mucosal involvement without stromal invasion was identified (Figure 3). The non-neoplastic endometrium was atrophic. The neoplastic cells were immunoreactive for p53 (Figure 4) and showed a high mitotic index on Ki-67 immunostain, supporting the morphologic impression. The clinical, morphologic examination, and immunohistochemical profile were classic for the so-called endometrial intraepithelial carcinoma (EIC).

Reduction mammoplasty is a frequently performed procedure for the treatment of macromastia and for the achievement of symmetry in breast cancer patients following lumpectomy. Slides from 516 consecutive bilateral reduction mammoplasties performed for macromastia over 15 years were reviewed. Among these, 92 (18%) low-risk ductal intraepithelial neoplasia/intraductal hyperplasia, 28 (5%) ductal intraepithelial neoplasia 1 (1 low-grade ductal carcinoma in situ, 11 atypical intraductal hyperplasia, and 16 flat type), 17 (3%) lobular intraepithelial neoplasia, and 1 (0.2%) tubular carcinoma were identified. The patients were categorized into 3 age groups: <40 (n = 352), 40 to 50 (n = 107), and over 50 years (n = 57); the frequency of the lesions increased with age. These data confirm the low frequency of clinically occult malignancies identified in reduction mammoplasty specimens and provide substantial information about the frequency of a variety of intraepithelial proliferations. Preoperative mammography, specimen orientation, and inking of margins with 1 color are advised when reduction mammoplasty is scheduled for women ≥ 40 years of age.

Exaggerated placental site (EPS) reaction is a reactive or an exuberant physiologic process involving intermediate trophoblasts infiltrating the underlying endomyometrium at the implantation site. Sharing similar cytological and immunohistochemical features with the tumor cells of placental site trophoblastic tumor, a biological link between the 2 lesions can be speculated. Because placental site trophoblastic tumor has a unique sex chromosomal requirement in its genome that requires a paternal X chromosome (i.e. a female antecedent gestation), we investigated whether EPS carries the similar genetic profile by DNA genotypic analysis. Twenty cases of EPS were reviewed and analyzed by AmpFlSTR Identifiler polymerase chain reaction amplification system (Applied Biosystems, Inc., Foster City, CA). The genetic profile of all cases demonstrated unique paternal alleles to that of the paired maternal tissue, confirming the trophoblastic origin of EPS. The presence of an XY genome (male) was identified in 11 cases (55%), and an XX genome (female) was seen in the rest of 9 cases (45%). Therefore, EPS is a trophoblastic lesion that can arise from either male or female gestations. The assignment of sex chromosomes in our study (XY, 55% and XX, 45%) does not support a neoplastic association between placental site trophoblastic tumor and EPS.

Gastrointestinal involvement by malignant melanoma is predominantly a metastatic phenomenon. Although primary malignant melanoma of the gastrointestinal tract has been documented in the esophagus, stomach, small bowel, and anorectum, the incidence of primary melanoma of the colon is rare and remains controversial in most cases. We present a case of solitary malignant melanoma of the transverse colon occurring in a 64-year-old African American male patient. Complete dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or an ocular primary lesion. Microscopic examination of the resection specimen revealed malignant melanoma, which was confirmed by immunohistochemical positivity for S100 and melan-A. We believe that this tumor represents a primary colonic malignant melanoma.

The p63 gene, a member of the p53 family, is an epithelial marker expressed in embryonic ectoderm, breast myoepithelium, prostate, oral epithelium, epidermis, and urothelium. The DeltaN-p63 isoforms of p63, which are believed to behave as oncogenes, are expressed in squamous cell carcinoma, basal cell carcinoma, and transitional cell carcinoma. Only a few authors have looked for p63 expression in thymomas and normal thymus. We, therefore, thought of undergoing such a search by taking advantage of our archival material. We studied 66 cases of thymoma (1 type A, 8 type AB, 12 type B1, 19 type B2, 12 type B3, and 14 type C/thymic carcinoma) and 10 specimens of normal human thymus arranged in tissue microarrays. All thymomas (including thymic carcinomas) were positive for p63 regardless of type. Most of the epithelial cells of the normal thymus were also positive for this marker.

Uniform management of flat DIN 1 (flat epithelial atypia) on core needle biopsy (CNB) concerning surgical excision or clinical follow-up are lacking. In a retrospective review of 1,751 CNB over an 8-year period, we found 63 cases with flat DIN 1 as the most advanced lesion; follow-up was available in 55 cases. Of the 63 patients, 24 had a subsequent biopsy for 15 days to 10 years after the initial CNB, an infiltrating carcinoma was found in nine (14.3%) patients, seven (11.1%) in the ipsilateral, and two (3.2%) in the contralateral breast. Five underwent an excisional biopsy of the ipsilateral breast within less than 3 months of the initial CNB; none had either an invasive or intraepithelial carcinoma. Based on our findings, we consider flat DIN 1 a marker of slightly increased risk for subsequent development of invasive breast carcinoma. When flat DIN 1 is found on CNB as the most advanced lesion after mammographic correlation, an excisional biopsy is not mandatory; however, close follow-up is advised with repeat mammograms for early detection of any clinically occult carcinoma in the vicinity of flat DIN 1 that may have been missed by the CNB.

Squamous cell carcinoma of the pancreas is a rare condition. The incidence has been estimated at approximately 1% of all pancreatic malignancies. The histogenesis is uncertain, but it has been proposed to originate from areas of squamous metaplasia of pancreatic ductal epithelium. We present a case of a 56-year-old man who presented with back pain and was found to have a squamous cell carcinoma of the pancreas without evidence of metastatic disease. Three months after en bloc resection with negative margins and lymph nodes, he presented with widely metastatic disease. A review of the literature on the topic is presented, and the poor prognosis of this rare tumor, despite complete surgical resection, is discussed.

Study Objective. To confirm that images observed at hysteroscopy correlate with histopathologic diagnoses.Design. Double-blind study (Canadian Task Force classification II-2).Setting. Gynecologic cancer center, private institute.Subjects. One thousand four hundred thirty-six uterine cavities.Intervention. Hysteroscopy.Measurements and Main Results. Images were classified as normal hysteroscopy, benign lesion, low-risk hyperplasia, high-risk hyperplasia, and carcinoma. A hysteroscopic diagnosis was made and biopsy specimens were obtained with Kevorkian-type curettes or Sims curettes. Tissues were studied by a pathologist, after which we compared endoscopic diagnoses with anatopathologic diagnoses. Significant correlation was found between suspicion based on images and histologic confirmation (p = 0.001). The Cramer V coefficient, which measures the relationship between both methods, was high: 0.925. The Cramer V coefficient takes values ranging from zero, to indicate lack of correlation, to 1, to indicate perfect correlation. A; symmetry coefficient of 0.96 is interpreted as probable improvement in the prediction of histologic diagnosis based on images.Conclusion. This classification system can be useful for a systematic approach to hysteroscopic findings and to improve communication among specialists. It is based on the degree of hysteroscopic suspicion aimed at early detection of endometrial cancer and its precursor lesions.