Desmoplastic trichoepithelioma versus morphoeic basal cell carcinoma
ER and PR status in ECOG 2197: comparing RT-PCR and immunohistochemistry
Triple negativity as a positive prognostic factor for survival in sentinel lymph node micrometastases
TTF-1 protein expression in ovarian epithelial neoplasms
Significance of occult axillary lymph node metastases in breast cancer
It is often difficult to differentiate between cases of desmoplastic trichoepithelioma (DTE) and morphoeic basal cell carcinoma (MBCC) because they have many features in common. The authors conducted a study to clarify which criteria for differentiation offer the best basis for diagnosis. They compared 19 cases of DTE histologically and immunohistochemically with 18 cases of MBCC using CD34, CD10 cytokeratin (CK) 20, androgen receptor, Bcl-2, Ki67, and p53 immunohistochemistry. The authors calculated sensitivity, specificity, and positive and negative likelihood ratios. Convincing diagnostic evidence for DTE was identified from the features of symmetry, good circumscription, and depression in the lesion’s center. However, these features are applicable only to excisional specimens, not specimens taken by punch biopsy. Signs of infundibular, follicular, or sebaceous differentiation, calcification, osteoma, association with a melanocytic nevus, and absence of solar elastosis below the lesion provided equally robust diagnostic evidence for DTE. Immunohistochemically, only staining of Merkel cells with CK20 and negativity of aggregations with androgen receptors were diagnostically convincing for DTE. Ki67 and p53 revealed significant differences but a lower positive likelihood ratio. The authors concluded that histopathologists need to identify with confidence subtle signs of infundibular, follicular, and sebaceous differentiation because these features are dependable criteria for differentiating DTE from MBCC. Immunohistochemistry for androgen receptors and CK20 is helpful, but interpretation is difficult for some DTEs when few cells are immunopositive for these markers.
Costache M, Bresch M, Böer A. Desmoplastic trichoepithelioma versus morphoeic basal cell carcinoma: a critical reappraisal of histomorphological and immunohistochemical criteria for differentiation. Histopathology. 2008: 52: 865–876.
Correspondence: Dr. Almut Böer at email@example.com
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Central and local laboratory concordance for hormone receptor measurement is important therapeutically. The authors conducted a study to compare estrogen receptor and progesterone receptor measured by local laboratory immunohistochemistry (IHC), central IHC, and central reverse-transcription polymerase chain reaction (RT-PCR) using a proprietary 21-gene assay. They evaluated a case-control sample of 776 breast cancer patients from Eastern Cooperative Oncology Group (ECOG) study E2197. Central IHC Allred score for estrogen and progesterone receptor was obtained using tissue microarrays and 1D5 ER antibody and 636 PR antibody. Quantitative RT-PCR for estrogen and progesterone receptor in whole sections was performed using the 21-gene assay. The authors found that the concordance between local and central IHC for estrogen receptor was 90 percent (95 percent confidence interval [CI], 88–92 percent), between local IHC and central RT-PCR was 91 percent (95 percent CI, 89–93 percent), and between central IHC and central RT-PCR was 93 percent (95 percent CI, 91–95 percent). The concordance between local IHC and central IHC for progesterone receptor was 84 percent (95 percent CI, 82–87 percent), between local IHC and central RT-PCR was 88 percent (95 percent CI, 85–90 percent), and between central IHC and central RT-PCR was 90 percent (95 percent CI, 88–92 percent). Although concordance was high, IHC estrogen receptor-negative cases that were RT-PCR positive were more common than IHC estrogen receptor-positive cases that were RT-PCR negative. In estrogen receptor-positive patients, estrogen receptor expression by central IHC Allred score was marginally associated with recurrence (P=.091), and estrogen receptor expression by central RT-PCR was significantly associated with recurrence (P=.014). However, recurrence score, which incorporates additional genes/ pathways, was a highly significant predictor of recurrence (P<.0001). The authors concluded that there is a high degree of concordance among local IHC, central IHC, and central RT-PCR by the proprietary gene assay for estrogen and progesterone receptor status. Although estrogen receptor expression is marginally associated with relapse in estrogen receptor-positive patients treated with chemohormonal therapy, recurrence score is a highly significant predictor of recurrence.
Badve SS, Baehner FL, Gray RP, et al. Estrogen- and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory. J Clin Oncol. 2008;26:2473–2481.
Correspondence: Dr. Sunil Badve at firstname.lastname@example.org
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Lymph node mapping and sentinel lymph node biopsy are used to stage patients with cutaneous malignant melanoma. Immunohistochemical stains help detect micrometastases; however, molecular biology techniques are associated with better diagnostic sensitivity. The authors conducted a study of sentinel lymph nodes in which they analyzed 60 nodes. The primary lesions were malignant melanoma stage I or II with followup of longer than two years. Sentinel lymph nodes were studied with hematoxylinandeosin, immunohistochemistry for S-100 and HMB-45, and molecular biology techniques (reverse transcription [RT]-PCR) for detecting tyrosinase messenger RNA. In 15 of 60 cases (25 percent), tyrosinase was detected by RT-PCR; three of these cases were also positive by immunohistochemistry. The population was divided into three groups: hematoxylinandeosin / immunohistochemistry+/molecular biology techniques+ (three cases); hematoxylinandeosin / immunohistochemistry–/molecular biology techniques+ (12 cases); and hematoxylinandeosin / immunohistochemistry / molecular biology techniques– (45 cases). Correlation of the three groups with overall survival showed that two of three patients in the first group died (67 percent); five of 12 in the second group died (42 percent); and all 45 patients in the third group were alive, with no lymphadenectomy and a median followup of 84 months. The authors concluded that including molecular biology techniques appears to be of great value for detecting sentinel lymph node micrometastases in patients with cutaneous malignant melanoma. In their study, those patients who showed negativity with all three methods had a null recurrence rate. Therefore, this triple negativity could be a positive prognostic factor for overall survival. The findings suggest the possibility of molecular oncological staging, which would allow patients with submicroscopic metastases to be selected for complete treatment.
Denninghoff VC, Falco J, Kahn AG, et al. Sentinel node in melanoma patients: triple negativity with routine techniques and PCR as positive prognostic factor for survival. Mod Pathol. 2008;21:438–444.
Correspondence: Dr. V. C. Denninghoff at email@example.com
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Thyroid transcription factor-1 (TTF-1) protein expression is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or thyroid, the expression of this marker has been studied in only a limited number of ovarian neoplasms. The authors examined the incidence of TTF-1 expression in a variety of ovarian epithelial neoplasms. Tissue microarrays of 138 ovarian serous carcinomas, 65 endometrioid adenocarcinomas, 35 mucinous adenocarcinomas, 30 mucinous neoplasms of low malignant potential, and 10 clear cell carcinomas were stained with anti-TTF1 antibody. In addition, whole tissue sections of 19 serous carcinomas, five endometrioid adenocarcinomas, seven mucinous adenocarcinomas, and three clear cell carcinomas were stained. In the tissue microarrays, TTF-1 nuclear expression was demonstrated in two of 65 (three percent) of the endometrioid adenocarcinomas; no nuclear immunoreactivity was identified in the remaining ovarian neoplasms. In the whole tissue sections, TTF-1 nuclear staining was present in seven of 19 (37 percent) serous carcinomas, one of five (20 percent) endometrioid adenocarcinomas, and one of three (33 percent) clear cell carcinomas. In most of the positive cases, staining was focal, but in one endometrioid adenocarcinoma in the tissue microarray and one serous and one clear cell carcinoma in the whole tissue sections, diffuse positivity was noted. Overall, there was nuclear staining in 0.7 percent of tumors in the tissue microarray and 26 percent in the whole tissue sections. The authors concluded that although TTF-1 nuclear expression is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional immunoreactivity of ovarian carcinomas should be considered in evaluating neoplasms of unknown primary origin. It should also be taken into consideration when evaluating adenocarcinomas involving the lung in patients with a history of gynecologic malignancy.
Kubba LA, McCluggage WG, Liu J, et al. Thyroid transcription factor-1 expression in ovarian epithelial neoplasms. Mod Pathol. 2008;21:485–490.
Correspondence: Dr. M. T. Deavers, Dept. of Pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009
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Sentinel lymph node biopsy in breast cancer allows the routine performance of serial sections or immunohistochemical staining, or both, to detect occult metastases missed by conventional techniques. However, there is no consensus regarding the optimal method for pathologic examination of such nodes or the prognostic significance of sentinel lymph node micrometastases. The authors conducted a study in which they re-examined axillary tissue blocks following their pathologic protocol for sentinel lymph nodes. The study involved 368 patients with axillary node-negative invasive breast cancer who, between 1976 and 1978, underwent mastectomy, axillary dissection, and no systemic therapy. Occult lymph node metastases were categorized by pattern of staining (immunohistochemically positive or negative, hematoxylinandeosin staining positive or negative), number of positive nodes (zero, one, or more than one), number of metastatic cells (zero, one to 20, 21 to 100, more than 100), and largest cluster size (=0.2 mm [pN0i+], 0.3 to 2.0 mm [pN1mi], >2.0 mm [pN1a]). The authors reported 20-year results as overall survival, disease-free survival, and disease-specific death. A total of 23 percent of patients (83 of 368) were converted to node positive. Of these, 73 percent were =0.2 mm in size (pN0i+), 20 percent were 0.3 to 2.0 mm (pN1mi), and six percent were more than 2 mm (pN1a). On univariate and multivariate analysis, pattern of staining, number of positive nodes, number of metastatic cells, and cluster size were all significantly related to disease-free survival and disease-specific death. On multivariate analysis, each of these measures had significance comparable to, or greater than, tumor size, grade, or lymphovascular invasion. The authors concluded that in breast cancer patients staged node negative by conventional single-section pathology, occult axillary node metastases detected by the authors’ pathologic protocol for sentinel lymph nodes are prognostically significant.
Tan LK, Giri D, Hummer AJ, et al. Occult axillary node metastases in breast cancer are prognostically significant: results in 368 node-negative patients with 20-year follow-up. J Clin Oncol. 2008;26:1803–1809.
Correspondence: Dr. Hiram S. Cody III at firstname.lastname@example.org
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Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.