Faculty Bibliography

Nuclear expression of the cell cycle inhibitor p27(KIP1) is reduced in a variety of human malignancies, including breast cancer. Loss of nuclear p27(KIP1) during tumor progression, documented by immunohistochemistry (IHC), has been studied for its potential prognostic implication. We examined by IHC the association between nuclear p27(KIP1) expression and hormone receptor status in T1N0M0 breast cancer. PATIENTS AND METHODS: The correlation between nuclear p27(KIP1) expression and estrogen (ER) and progesterone (PR) hormone receptor status was analyzed in 122 human T1N0M0 (68 T1a/b, 54 T1c) breast cancer specimens. All patients were staged as N0 by axillary node dissection. RESULTS: A statistically significant reduction in p27(KIP1) expression was observed as tumor size increased from T1a/b (7%) to T1c (22%). The proportion of tumors with low nuclear p27(KIP1) expression was higher in the ER-negative/PR-negative group compared to the ER-positive/PR-positive group, but this difference was only statistically significant in the T1a/b subgroup (p=0.0007). CONCLUSION: Further investigations into causes of p27(KIP1) deregulation and their relationship to hormone receptor expression in T1N0M0 breast ductal carcinomas are warranted. Such studies may help identify prognostic, as well as predictive, markers of therapy resistance

Purpose. The purpose of this study was to compare the surgical and pathological variables which impact rate of re-excision following breast conserving therapy (BCS) with or without concurrent additional margin excision (AM). Methods. The pathology database was queried for all patients with DCIS from January 2004 to September 2008. Pathologic assessment included volume of excision, subtype, size, distance from margin, grade, necrosis, multifocality, calcifications, and ER/PR status. Results. 405 cases were identified and 201 underwent BCS, 151-BCS-AM, and 53-mastectomy. Among the 201 BCS patients, 190 underwent re-excision for close or involved margins. 129 of these were treated with BCS and 61 with BCS-AM (P < .0001). The incidence of residual DCIS in the re-excision specimens was 32% (n = 65) for BCS and 22% (n = 33) for BCS-AM (P < .05). For both the BCS and the BCS-AM cohorts, volume of tissue excised is inversely correlated to the rate of re-excision (P = .0284). Multifocality (P = .0002) and ER status (P = .0382) were also significant predictors for rate of re-excision and variation in surgical technique was insignificant. Conclusions. The rate of positive margins, re-excision, and residual disease was significantly higher in patients with lower volume of excision. The performance of concurrent additional margin excision increases the efficacy of BCS for DCIS.

BACKGROUND: Complete lymph node dissection, the current standard treatment for nodal metastasis in melanoma, carries the risk of significant morbidity. Clinically apparent nodal tumor is likely to impact both preoperative lymphatic function and extent of soft tissue dissection required to clear the basin. We hypothesized that early dissection would be associated with less morbidity than delayed dissection at the time of clinical recurrence. MATERIALS AND METHODS: The Multicenter Selective Lymphadenectomy Trial I randomized patients to wide excision of a primary melanoma with or without sentinel lymph node biopsy. Immediate completion lymph node dissection (early CLND) was performed when indicated in the SLN arm, while therapeutic dissection (delayed CLND) was performed at the time of clinical recurrence in the wide excision-alone arm. Acute and chronic morbidities were prospectively monitored. RESULTS: Early CLND was performed in 225 patients, and in the wide excision-alone arm 132 have undergone delayed CLND. The 2 groups were similar for primary tumor features, body mass index, basin location, and demographics except age, which were higher for delayed CLND. The number of nodes evaluated and the number of positive nodes was greater for delayed CLND. There was no significant difference in acute morbidity, but lymphedema was significantly higher in the delayed CLND group (20.4% vs. 12.4%, P = .04). Length of inpatient hospitalization was also longer for delayed CLND. CONCLUSION: Immediate nodal treatment provides critical prognostic information and a likely therapeutic effect for those patients with nodal involvement. These data show that early CLND is also less likely to result in lymphedema

BACKGROUND: Although histopathologic identification of regression of melanoma is usually straightforward, sometimes it can be difficult to distinguish it from scarring fibrosis. Therefore, this study investigates the elastic fiber pattern in melanomas associated with either regression or scars. METHODS: We compared 33 invasive melanomas with the fibrosing stage of regression to 10 cases of invasive melanomas with scarring fibrosis. None of the regression cases had a prior surgical procedure. Elastic fiber patterns were evaluated with Verhoeff's elastic van Gieson stain (EVG) and elastin immunostain. RESULTS: Elastin immunostain was superior to EVG in revealing the elastic fiber patterns. Both regression and scars had decreased to absent elastic fibers in the areas of fibrosis. However, areas of regression had a well-defined compressed layer of thin elastic fibers pushed down from the papillary dermis to the base of the fibrosis. In contrast, the base of scars lacked this compressed elastic layer and had instead an abrupt transition to the thick elastic fibers of the spared reticular dermis. CONCLUSIONS: We have identified distinct changes of the elastic tissue network, which more accurately define the presence of regression in melanoma and distinguish it from scarring fibrosis

OBJECTIVE: To describe an unusual case of papillary thyroid carcinoma presenting as a skin lesion on the nose. METHODS:We describe the clinical, pathologic, and immunohistochemistry findings of the patient and briefly review the relevant literature. RESULTS: An asymptomatic 73-year-old man noted a skin lesion on his nose, which when biopsied, revealed histopathologic characteristics consistent with papillary thyroid cancer and was immunohistochemistry positive for thyroid transcription factor-1 and thyroglobulin, also consistent with a neoplasm of thyroid origin. Subsequent physical examination showed a large left thyroid mass, and further workup demonstrated invasion of the trachea and surrounding musculature. In addition, metastases to the sternum, spine, lungs, and liver were noted. Fine-needle aspiration biopsy performed on the thyroid mass confirmed papillary thyroid carcinoma. Although there was evidence of systemic metastases, total thyroidectomy was suggested to the patient to allow optimal treatment by radioactive iodine. At operation, the cancer demonstrated fixation to the trachea and musculature, as well as infiltration of the surrounding soft tissues. Only the portion of the left thyroid mass that could be mobilized was removed. Final pathologic examination confirmed papillary thyroid carcinoma. Cutaneous metastases of thyroid carcinoma are infrequent, and, as the presenting feature of thyroid carcinoma, are even more rare. This case is noteworthy because a skin lesion was the presenting feature of thyroid carcinoma and histopathologic findings together with immunophenotyping provided the initial diagnosis. CONCLUSIONS: In this patient, as in most published cases, the cutaneous metastasis was shown to occur in the setting of extensive metastases. This case also demonstrates that papillary thyroid carcinoma in men older than age 50 years can behave very aggressively