Primary adnexal adenocarcinoma of the vulva: A diagnosis of exclusion based on location, immunohistochemistry, and pattern of spread.

► Vulvar adenocarcinomas are rare comprising less than 0.1% of primary malignancies of the vulva. ► The diagnosis of primary vulvar adenocarcinomas remains a challenge due to its rarity, variation in histological appearance, and limited literature. ► The basis of the diagnosis includes morphology, immunohistochemistry, clinical history and pattern of spread.

p53 Expression in node-positive breast cancer patients: results from the Cancer and Leukemia Group B 9344 Trial (159905).

PURPOSE: p53 as a prognostic and predictive factor in early-stage breast cancer has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel [Cancer and Leukemia Group B (CALGB) 9344, INT0148]. PATIENTS AND METHODS: Epithelial p53 expression was evaluated using two immunohistochemical antibodies (DO7 and 1801) in formalin-fixed, paraffin-embedded tissue from patients with node-positive breast cancer who were randomized to four cycles of cyclophosphamide and one of three doses of doxorubicin (60, 75, or 90 mg/m(2); AC) and to receive four subsequent cycles of paclitaxel (T) or not. Prognostic and predictive value of p53 protein expression was assessed, independent of treatment assignment, for escalating doses of doxorubicin or addition of T with endpoints of relapse-free (RFS) and overall survival (OS). RESULTS: Of 3,121 patients, 1,887 patient specimens treated on C9344 were obtained, passed quality control, and evaluated for p53 expression. Expression was 23% and 27% for mAbs 1801 and D07, respectively, with 92% concordance. In univariate analysis, p53 positivity was associated with worse OS with either antibody, but only p53 staining with monoclonal antibody 1801 had significantly worse RFS. In multivariate analysis, p53 was not predictive of RFS or OS from either doxorubicin dose escalation or addition of paclitaxel regardless of the antibody. CONCLUSION: Nuclear staining of p53 by immunohistochemistry is associated with worse prognosis in node-positive patients treated with adjuvant doxorubicin-based chemotherapy but is not a useful predictor of benefit from doxorubicin dose escalation or the addition of paclitaxel.

Cancer and Leukemia Group B Pathology Committee guidelines for tissue microarray construction representing multicenter prospective clinical trial tissues.

Practice-changing evidence requires confirmation, preferably in multi-institutional clinical trials. The collection of tissue within such trials has enabled biomarker studies and evaluation of companion diagnostic tests. Tissue microarrays (TMAs) have become a standard approach in many cooperative oncology groups. A principal goal is to maximize the number of assays with this precious tissue. However, production strategies for these arrays have not been standardized, possibly decreasing the value of the study. In this article, members of the Cancer and Leukemia Group B Pathology Committee relay our experiences as array facility directors and propose guidelines regarding the production of high-quality TMAs for cooperative group studies. We also discuss statistical issues arising from having a proportion of patients available for TMAs and the possibility that patients with TMAs fail to represent the greater study population.

Dendriform pulmonary ossification, a form of diffuse pulmonary ossification: report of a 26-year autopsy experience.

CONTEXT: Dendriform pulmonary ossification (DPO) is an uncommon form of diffuse pulmonary ossification that typically affects the pulmonary interstitium in a setting of interstitial fibrosis. OBJECTIVE: To determine the incidence and characteristics of DPO and correlate the clinical, radiographic, and pathologic features in order to better understand its pathogenesis and behavior and facilitate proper therapy. DESIGN: Adult autopsies performed at a tertiary care center from 1978 to 2004 were reviewed to identify cases of DPO. Clinical, radiographic, and pathologic findings, including ultrastructural studies in select cases, were analyzed and correlated. RESULTS: Eight cases of DPO were identified from 1393 adult autopsies. None of the cases was diagnosed antemortem. The prevalence of DPO was 0.5%, and the incidence was 0.28 cases per year. Most patients had a history of chronic lung disease, and all were 65 years of age or older. CONCLUSIONS: Dendriform pulmonary ossification is an uncommon and unusual entity seen incidentally at autopsy and associated with chronic lung disease. It is well demonstrated in postmortem examination, confirmed by microscopy and ultrastructural study, but rarely diagnosed and virtually never considered clinically. Clinical diagnoses include bronchiectasis and interstitial pneumonitis based on radiographic evidence. With its associated radiographic/pathologic findings, DPO should be considered in the differential diagnosis of chronic lung disease.

The relevance of occult axillary micrometastasis in ductal carcinoma in situ: a clinicopathologic study with long-term follow-up.

BACKGROUND: Ductal carcinoma in situ (DCIS) represents 20% of newly diagnosed breast carcinoma cases. Historically, the incidence of axillary metastasis in DCIS has been small (1-2%) and its significance has been debated. It is widely known that serial sections of lymph nodes coupled with keratin immunohistochemistry (IHC) increases identification of micrometastasis. The advent of sentinel lymph node evaluation underscores the need to reevaluate the significance of occult micrometastases in DCIS. METHODS: Patients with DCIS and negative axillary lymph nodes from 1974 to 1992 were selected from the Saint Barnabas Medical Center Tumor Registry. All diagnoses were confirmed, and paraffin blocks were retrieved after acceptance into the study. Seven serial sections were obtained from each block and evaluated with two cytokeratin IHC stains. Clinical follow-up ranged from 10 to 28 years. RESULTS: One hundred two patients were included in the study. Micrometastases were identified in 13 patients (13%), mostly on 1 level and composed of microscopic clusters in the subcapsular sinus. Seven of these lymph node-positive patients (58%) had high-grade comedo DCIS, 4 (33%) had intermediate grades of various types of DCIS, and one had a low-grade micropapillary DCIS. The overall disease recurrence rate was 12%, but micrometasis was not detected in any of the patients who developed disease recurrence. CONCLUSIONS: Serial IHC evaluation of lymph nodes dramatically increased the identification of occult micrometastasis. However, IHC detected micrometastasis has no apparent clinical significance in DCIS, based on the current long-term clinicopathologic study. Therefore, the authors questioned the significance of occult micrometastasis, identified by IHC, in DCIS of any type and extent. Further evaluation and follow-up of lymph node micrometastases in patients with invasive tumors of various sizes are needed. The current findings would not support altering the stage of patients with DCIS and micrometastasis detected by IHC only.

Villous adenoma of the extrahepatic biliary tract: a rare entity.

Patients presenting with large obstructing extrahepatic biliary tumors often are presumed to have cholangiocarcinoma and are labeled with a grim disease with a poor prognosis, given little hope for a cure, and may actually opt for palliative care only. In some instances, however, the diagnosis is that of biliary adenoma (benign until it undergoes malignant degeneration), which can be confirmed via resection and pathologic evaluation of the lesion. Removal of the tumor in its benign stage then provides curative treatment of the obstructing lesion with excellent patient recovery and overall prognosis. We present a rare instance of observation of the presence of high-grade dysplasia in a large villous adenoma arising from the left hepatic duct with relief of biliary obstruction and curative resection.