College of American Pathologists
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  Anatomic Abstracts





April 2011

Michael Cibull, MD
Melissa Kesler, MD
Rouzan Karabakhtsian, MD
Megan Zhang, MD

Spectrum of acute generalized exanthematous pustulosis and its differentiation from GPPt Spectrum of acute generalized exanthematous pustulosis and its differentiation from GPP

The authors sought to discriminate acute generalized exanthematous pustulosis from generalized pustular psoriasis. AGEP is a severe, acute, pustular skin reaction, most often induced by drugs. It can be difficult to differentiate AGEP from generalized pustular psoriasis (GPP) clinically and histopathologically. The authors conducted a retrospective, descriptive, comparative histopathological study using step sections of 43 biopsies from 29 cases with a validated diagnosis of probable or definite AGEP and 24 biopsies from 19 cases with an established diagnosis of GPP. The authors found that in AGEP, biopsies from erythema and pustules showed minor differences, whereas histopathology of the acute stage of GPP showed major differences compared to the chronic stage. When they compared AGEP and GPP, they found that the presence of eosinophils, necrotic keratinocytes, and a mixed interstitial and mid-dermal perivascular infiltrate, as well as the absence of tortuous or dilated blood vessels, favored AGEP. Moreover, they found that chronic GPP was characterized by prominent epidermal psoriatic changes. The frequency of a psoriatic background of AGEP patients in the authors’ study was higher than that of psoriasis in the general population. However, the histopathology of a subgroup of AGEP patients with a personal history of psoriasis revealed no significant differences from that of the other AGEP patients. The authors concluded that despite considerable overlap, subtle, consistent, histopathological differences and the grade of severity of specific features can help in differentiating between AGEP and GPP. The authors could not substantiate earlier reports that follicular pustules exclude AGEP, nor did they find that vasculitis is a specific feature in AGEP. They believe their study supports the concept that AGEP is a separate entity that is distinct from GPP.

Kardaun SH, Kuiper H, Fidler V, et al. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol. 2010;37:1220–1229.

Correspondence: Dr. Sylvia H. Kardaun at
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Evaluation of vascular space involvement in endometrial adenocarcinomas Evaluation of vascular space involvement in endometrial adenocarcinomas

To better understand “vascular pseudoinvasion” in total laparoscopic hysterectomies with endometrial carcinoma, the authors compared pathologic findings in these laparoscopic and total abdominal hysterectomies performed for uterine endometrioid adenocarcinoma. Reports from 58 robotically assisted laparoscopic and 39 abdominal hysterectomies with grades one or two endometrioid endometrial adenocarcinomas were reviewed for stage, depth of invasion, vascular space involvement, uterine weight, and lymph node metastases. The authors also looked at possible procedural artifacts, including vertical endomyometrial clefts, inflammatory debris, benign endometrial glands, and disaggregated tumor cells in vascular spaces. Three gynecologic pathologists reviewed all foci with vascular involvement. Nine of the 58 (16 percent) laparoscopic and three of the 39 (seven percent) abdominal hysterectomies contained vascular space involvement based on the original pathology reports (P=0.0833). No one histologic feature consistently distinguished laparoscopic from abdominal cases on blind review of the available cases. Disaggregated intravascular tumor cells were significantly associated with reported vascular involvement in both procedures (P=<0.001 and 0.016), most of which were corroborated on review. Laparoscopic procedures tend to have a higher index of vascular involvement, which is associated with lower stage, fewer lymph node metastases, and less myometrial invasion. However, pathologists cannot consistently determine the procedure on histologic findings alone. Moreover, there is significant inter-observer variability in distinguishing true from artifactual vascular space involvement, even among pathologists at the same institution. The clinical significance of vascular space involvement seen adjacent to artifacts is unclear, as is the impact of laparoscopic hysterectomy on recurrence risk.

Folkins AK, Nevadunsky NS, Saleemuddin A, et al. Evaluation of vascular space involvement in endometrial adenocarcinomas: laparoscopic vs abdominal hysterectomies. Mod Pathol. 2010;23:1073–1079.

Correspondence: Dr. M. S. Hirsch at
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P16-positive oropharyngeal SCC: an entity with a favorable prognosis regardless of tumor HPV status P16-positive oropharyngeal SCC: an entity with a favorable prognosis regardless of tumor HPV status

In the human papillomavirus era, the best way to assess oropharyngeal squamous cell carcinoma for risk stratification is not clear, although use of p16 immunohistochemistry and human papillomavirus (HPV) in situ hybridization (ISH) have been recommended. A significant minority of tumors are p16 positive and HPV-ISH negative. The authors tested 239 oropharyngeal squamous cell carcinomas (SCCs) for p16 using immunohistochemistry and for high-risk HPV using ISH. For p16-positive, HPV-ISH–negative cases, PCR was conducted for HPV. The findings were correlated with pathologic and clinical findings. The authors found that of the 239 cases, 187 (78 percent) were positive for p16. And of this group, 139 (74 percent) were positive for HPV by ISH. Of the remaining 48 cases, 45 had material for PCR. Nineteen were positive for HPV, leaving a group of 26 p16-positive and HPV-undetectable SCCs. In the p16-positive cohort, no difference in survival was noted between cases that were HPV-ISH positive versus negative. Comparing the HPV-ISH–positive and HPV-ISH–negative and PCR-negative SCCs, again, no difference in survival was noted. In univariate and multivariate analysis, patients with p16-positive, HPV-negative SCC still had significantly better survival rates than those with p16-negative SCC. The authors concluded that outcomes for p16-positive, HPV-negative oropharyngeal SCC are not significantly different than those for p16-positive, HPV-positive tumors, and they are significantly better than those for p16-negative tumors. These results suggest that p16 immunohistochemistry alone is the best test for risk stratification in oropharyngeal SCC.

Lewis JS Jr., Thorstad WL, Chernock RD, et al. p16 positive oropharyngeal squamous cell carcinoma: an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34(8):1088–1096.

Correspondence: Dr. James S. Lewis Jr. at
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Molecular testing for lipomatous tumors: critical analysis and test recommendations Molecular testing for lipomatous tumors: critical analysis and test recommendations

Ancillary molecular testing has been advocated for its diagnostic accuracy in differentiating lipomas from atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL). However, the implications of such testing and the test’s specific indications for use are not well-established in the literature. The authors conducted a study in which they expanded on previous findings by quantitatively evaluating the impact of molecular testing of lipomatous neoplasms in their routine clinical practice. They also assessed the effect of distinct surgical procedures in modulating the risk of local recurrence for lipomatous tumors after molecular classification. The authors analyzed 405 lipomatous neoplasms located in the trunk and extremities. The neoplasms were analyzed histologically and for the presence of 12q13-15 amplification on paraffin-embedded tissues by assessing MDM2/CPM amplification. Survival analyses were calculated with the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was evaluated by the Cox regression method. The 405 tumors were classified histologically as ordinary lipoma (n=324), intramuscular lipoma (n=29), and ALT/WDL (n=52). The level of agreement between the histologic and molecular diagnoses was high (96 percent), but pathologists showed a tendency to overestimate cytologic atypia and the diagnosis of ALT/WDL (precision, 79 percent; accuracy, 88 percent). Molecular assessment led to a major diagnostic reclassification of 18 tumors (four percent). Eleven of the tumors classified histologically as ALT/WDL were reclassified as ordinary lipoma (n=5) and intramuscular lipoma (n=6), and none of them recurred. Seven ordinary lipomas were reclassified as ALT/WDL, six of which were larger than 15 cm and deeply located; two of them recurred locally. After assessing molecular data, the five-year local recurrence rates for ordinary lipoma, intramuscular lipoma, and ALT/WDL were one percent, 12 percent, and 44 percent, respectively. Multivariate analyses after molecular assessment showed tumor type and type of resection to be associated with risk of local recurrence. The authors concluded that complementary molecular testing refines the histologic classification of lipomatous tumors and better estimates the impact of surgical procedures on risk of local recurrence. Pathologists tend to overestimate the degree of cytologic atypia. The indiscriminate use of molecular testing should be avoided, especially for extremity-based tumors. Molecular testing should be considered for relapsing lipomas, tumors with questionable cytologic atypia (even if widely excised), and large lipomatous tumors (over 15 cm) without diagnostic cytologic atypia.

Zhang H, Erickson-Johnson M, Wang X, et al. Molecular testing for lipomatous tumors: critical analysis and test recommendations based on the analysis of 405 extremity-based tumors. Am J Surg Pathol. 2010;34(9):1304–1311.

Correspondence: Dr. Andre M. Oliveira at
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Progression from low- to high-grade squamous intraepithelial lesion Progression from low- to high-grade squamous intraepithelial lesion

Accurately assessing progression from low- to high-grade squamous intraepithelial lesion of the cervix (cervical intraepithelial neoplasia [CIN]2 or CIN3) is critical in ascertaining high-grade squamous intraepithelial lesion (HSIL) outcome risk, the value of predictive biomarkers, and the need for excisional therapy. To assess this risk, the authors obtained biopsy outcome data on a series of squamous intraepithelial lesions initially diagnosed as low grade. Consecutive biopsy diagnoses of low-grade squamous intraepithelial lesion (LSIL) were obtained from the archives, and the frequency of HSIL biopsy outcomes were ascertained by record and histological review. Then a numerical severity score was recorded for each diagnosis: LSIL (one to two), CIN2 (three to four), and CIN3 (five to six), with lower and higher values corresponding to the degree (low versus high) of histological severity within each category, respectively. Of 264 initial LSILs, 29 (11 percent) were reported with an HSIL outcome. However, histological review of 21 of these HSILs confirmed only eight (38 percent) HSIL diagnoses by review with the numerical severity score: three cases scored as five, three as four, and two as three. The remaining 13 cases were assigned a numerical severity score of one or two. P16 immunostains of corresponding previous and subsequent biopsies were discordant in four of 12 cases (33 percent). In a blind review of a randomly selected series of HSILs from the same practice, HSIL was significantly more likely to be confirmed on re-review (10 of 13 [77 percent]; P=0.024). These findings show that confirmed HSIL outcomes (on review) following an LSIL biopsy are infrequent (approximately three percent). The authors concluded that a diagnosis of HSIL following an LSIL should always be reviewed because this diagnostic pairing may be more likely to be associated with a diagnostic error.

Chen EY, Tran A, Raho CJ, et al. Histological ‘progression’ from low (LSIL) to high (HSIL) squamous intraepithelial lesion is an uncommon event and an indication for quality assurance review. Mod Pathol. 2010;23:1045–1051.

Correspondence: Dr. C. P. Crum at
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.