College of American Pathologists
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  Anatomic Abstracts





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December 2003

Appendiceal mucinous neoplasms
The classification of appendiceal mucinous tumors is controversial, and the terminology applied to them is inconsistent, particularly when they lack overtly malignant features but are associated with extra-appendiceal spread. The authors reviewed 107 appendiceal mucinous neoplasms and classified them as low-grade appendiceal mucinous neoplasm (LAMN; n=88), mucinous adenocarcinoma (MACA; n=16), or discordant (n=3) based on architectural and cytologic features. Thirty-nine tumors were confined to the appendix, but 49 had extra-appendiceal tumor spread, including 39 with peritoneal tumor characterized by mucin pools harboring low-grade mucinous epithelium, usually dissecting in a hyalinized stroma. Eight of the 16 MACAs lacked destructive invasion of the appendiceal wall, and eight showed an infiltrative pattern of invasion. Extra-appendiceal tumor spread was present in 12 MACAs (four peritoneum, seven peritoneum and ovaries, one ovaries only). In MACAs with an infiltrative pattern, peritoneal tumor consisted of glands and single cells in a desmoplastic stroma. The peritoneal tumor in the remaining cases consisted of mucin pools that contained mucinous epithelium with high-grade atypia and, in some cases, increased cellularity compared with that seen in peritoneal spread in cases of LAMN. Three cases were classified as discordant because the appendiceal tumors were LAMNs but the peritoneal tumors were high grade. Followup was available for 49 LAMNs, 15 MACAs, and two discordant cases. None of the patients with LAMNs confined to the appendix experienced recurrence (median followup, six years). LAMNs with extra-appendiceal spread were associated with three-, five-, and 10-year survival rates of 100 percent, 86 percent, and 45 percent, respectively. Patients with MACA had three- and five-year survival rates of 90 percent and 44 percent, respectively (P=0.04). The bulk of peritoneal disease correlated with prognosis among patients with MACAs (P=0.04) and, to a lesser degree, among patients with LAMNs (P=0.07). The authors concluded that appendiceal mucinous neoplasms can be classified as low-grade mucinous neoplasms or mucinous adenocarcinoma based on architectural and cytologic features; tumors that can be confidently placed in the low-grade group (which requires rigorous pathologic evaluation of the appendix) and are confined to the appendix are clinically benign; low-grade tumors confined to the appendix are morphologically identical to those with extra-appendiceal spread (except for the usual identification of breach of the wall in the latter cases), and the same designation is appropriate for the appendiceal neoplasia in each situation; the long-term outlook for patients with low-grade tumors and peritoneal spread is guarded, with just over half dying of disease after 10 years; appendiceal mucinous tumors with destructive invasion of the appendiceal wall, complex epithelial proliferations, or high-grade nuclear atypia generally pursue an aggressive clinical course and should be classified as mucinous adenocarcinoma; peritoneal tumor can be classified as involvement by LAMN or MACA, and this distinction is of prognostic significance; bulky peritoneal tumor worsens prognosis; and LAMNs associated with high-grade peritoneal tumor behave as adenocarcinoma.

Misdraji J, Yantiss RK, Graeme-Cook FM, et al. Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107 cases. Am J Surg Pathol. 2003;27(8):1089-1103.

Reprints: Dr. Joseph Misdraji, Dept. of Pathology, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114;

Risk of subsequent CIN grade 2 or 3 among women with LSIL and HPV-positive ASCUS
The authors conducted a study to determine the risk of cumulative cervical intraepithelial neoplasia (CIN) grade 2 or 3 according to initial colposcopy and directed biopsy results among women with low-grade squamous intraepithelial lesions (LSIL) or human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS). A two-year followup of 897 cases of LSIL and 1,193 cases of HPV DNA-positive ASCUS from the ASCUS/LSIL Triage Study was used to simulate the recommendations of the American Society for Colposcopy and Cervical Pathology consensus conference. Women with CIN grade 1 or less were followed up for two years by semiannual cytologic examination with universal exit colposcopy. The clinical end point was a cumulative clinical center histologic diagnosis of CIN grade 2 or 3. The cumulative risk of CIN grade 2 or 3 was equivalent for LSIL (27.6 percent) and HPV-positive ASCUS (26.7 percent). After excluding the women with a diagnosis of CIN grade 2 or 3 at initial colposcopy and directed biopsy (17.9 percent), the remaining women were at nearly identical risk for subsequent CIN grade 2 or 3, regardless of initial colposcopy result (completely negative colposcopy-11.3 percent; negative colposcopically directed biopsy-11.7 percent; and CIN grade 1 biopsy-13 percent). The authors concluded that LSIL and HPV-positive ASCUS are clinically equivalent. Initial colposcopic detection of obviously prevalent CIN grade 2 or 3 reduces risk. However, for the remaining women who have CIN grade 1 or less on colposcopy and directed biopsy, the risk for subsequent CIN grade 2 or 3, whether missed, prevalent, or truly incident, is approximately 12 percent over two years. This risk does not vary meaningfully by initial distinction of histologic CIN grade 1 from negative colposcopy and biopsy.

Cox JT, Schiffman M, Solomon D, et al. Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy. Am J Obstet Gynecol. 2003; 188: 1406-1412.

Reprints: Dr. Diane Solomon, Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, NIH, DHHS, Executive Plaza North, Room 2123, Rockville, MD 20852;

Grading of atypia in nevi: correlation with melanoma risk
Nevi with architectural disorder and cytologic atypia of melanocytes, or dysplastic nevi, have varying degrees of histologic abnormalities, which can be considered on a spectrum of grades of atypia. Somewhat controversial and subjective criteria have been developed for grading NAD into three categories-mild, moderate, and severe. Grading involves architectural and cytological features, which often correlate. The architectural criteria are intraepidermal junctional extension beyond any dermal component, complex distortion of rete ridges, and dermal fibrosis. The cytological criteria are based on nuclear size, dispersion of chromatin, prominence of nucleoli, hyperchromasia, and variation in nuclear staining. Few tests have centered on the relationship between specific grades of atypia and risk for melanoma. The authors conducted a retrospective review of pathology reports involving 20,275 nevi examined between 1989 and 1996. From the total, 6,275 nevi in 4,481 patients were diagnosed as NAD. The patients were divided into groups based on whether they had mild (2,504), moderate (1,657), or severe (320) NAD. Review of accession data revealed that a personal history of melanoma was present in 5.7 percent of patients with mild atypia, 8.1 percent with moderate atypia, and 19.7 percent with severe atypia. The male/female ratios were similar in each group. In the three groups, the mean ages of the men were similar, as were the mean ages of the women, but the mean ages of the men tended to be six to 11 years older than that of the women in each group. Family history of melanoma was not considered. The odds ratio as a measure of association between NAD and personal history of melanoma was 4.08 (2.91-5.7) for NAD-severe versus NAD-mild, 2.81 (2-3.95) for NAD-severe versus NAD-moderate, and 1.45 (1.13-1.87) for NAD-moderate versus NAD-mild. These data show that the probability of having a personal history of melanoma, for any given NAD patient, correlates with NAD grade. Likewise, the risk of melanoma is greater for people who tend to produce nevi with high-grade histological atypia.

Arumi-Uria M, McNutt NS, Finnerty B. Grading of atypia in nevi: correlation with melanoma risk. Mod Pathol. 2003; 16(8): 764-771.

Reprints: Dr. N. Scott McNutt, Dermatopathology (F309), Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021;