Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma.

Follicular lymphoma (FL) constitutes the second most common non-Hodgkin lymphoma in the western world. FL carries characteristic recurrent structural genomic aberrations. However, information regarding the coding genome in FL is still evolving. Here, we describe the results of massively parallel exome sequencing and single nucleotide polymorphism 6.0 array genomic profiling of 11 highly purified FL cases, and 1 transformed FL case and the validation of selected mutations in 102 FL cases. We report the identification of 15 novel recurrently mutated genes in FL. These include frequent mutations in the linker histone genes HIST1H1 B-E (27%) and mutations in OCT2 (also known as POU2F2; 8%), IRF8 (6%), and ARID1A (11%). A subset of the mutations in HIST1H1 B-E affected binding to DNMT3B, and mutations in HIST1H1 B-E and in EZH2 or ARID1A were largely mutually exclusive, implicating HIST1H1 B-E in epigenetic deregulation in FL. Mutations in OCT2 (POU2F2) affected its transcriptional and functional properties as measured through luciferase assays, the biological analysis of stably transduced cell lines, and global expression profiling. Finally, multiple novel mutated genes located within regions of acquired uniparental disomy in FL are identified. In aggregate, these data substantially broaden our understanding of the genomic pathogenesis of FL.

Is duct excision still necessary for all cases of suspicious nipple discharge?

Despite the low likelihood of malignancy, it is recommended that all women with pathologic nipple discharge undergo duct excision based on the inadequate sensitivity of diagnostic modalities. However, these data originates prior to recent improvements in breast imaging. We performed a retrospective review of patients evaluated in the setting of modern diagnostic breast imaging. Of 175 women referred to our breast clinic with a primary complaint of nipple discharge, 142 (81%) had suspicious discharge. Of the 23 patients who opted for observation over duct excision, with a mean follow-up of 3.3 years, none have been diagnosed with cancer. Among patients who proceeded with surgery, cancer was diagnosed in seven patients (5%). Six of the seven patients had either an abnormal mammogram or ultrasound. Among 46 patients with suspicious nipple discharge, a normal physical exam and normal diagnostic mammogram/ultrasound, only one malignancy (2%) was identified in a 79-year-old patient with a personal history of breast cancer. In selected patients with suspicious nipple discharge, but normal physical exam and diagnostic imaging, short-term observation with repeat evaluation seems reasonable for patients who do not desire duct excision.

Is a level III dissection necessary for a positive sentinel lymph node in melanoma?

BACKGROUND: For melanoma patients with a positive axillary SLN, the extent of ALND remains controversial, with debate over whether a level III dissection is needed. METHODS: We queried our IRB approved prospective database for patients with a positive axillary SLN who had a level I/II dissection only, and compared recurrence and complication rates to the existing literature. RESULTS: Between 1998 and 2008, 270 patients had 285 level I/II ALNDs for a positive SLN. Median number of SLN removed was 2, while the median number of involved SLN was 1 (range 1-4). An average of 18.7 nodes/ALND were removed, with 13% having positive non-SLN. Post-operative complications occurred in 31 patients (11%), primarily cellulitis (8%). After a mean follow-up of 44 months, 14 patients had a regional recurrence in the axillary basin (5%). CONCLUSIONS: The complication rate and regional recurrence rate for patients undergoing a level I/II ALND for a positive SLN are either lower than or on par with reported series of ALND for level I, II, and III dissections, suggesting that in this setting, the level III dissection may be of minimal benefit.

Dermatofibrosarcoma protuberans: how wide should we resect?

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor with local recurrence rates ranging from 0 to 50%. Controversy exists regarding margin width and excision techniques, with some advocating Mohs surgery and others wide excision (WE). We reviewed the experience in two tertiary centers using WE with total peripheral margin pathologic evaluation. MATERIALS AND METHODS: Institutional Review Board approved retrospective review of patients with DFSP from 1991 to 2008. Patients had initial WE using 1-2 cm margins with primary or delayed closure; further excision was done whenever feasible for positive margins. Pathologic analysis included en face sectioning. We evaluated margin width, number of WE, reconstruction methods, radiation, and outcomes. RESULTS: A total of 206 DFSP lesions in 204 patients (76 males, 128 females), median age 41 years (range 1-84) were treated. Locations were trunk (135), extremities (43), and head and neck (28). The median number of excisions to achieve negative margins was 1 (range 1-4) with a median excision width of 2 cm (range 0.5-3 cm). Closure techniques included primary closure (142; 69%), skin grafting (52; 25%), and tissue flaps (9; 4%). There were 9 patients who received postoperative radiation, 6 for positive margins after maximal surgical excision. At a median follow-up of 64 months (range 1-210), 2 patients (1%) with head and neck primaries recurred locally. CONCLUSIONS: Using a standardized surgical approach including meticulous pathologic evaluation of margins, a very low recurrence rate (1%) was achieved with relatively narrow margins (median 2 cm), allowing primary closure in 69% of patients. This approach spares the additional morbidity associated with wider resection margins and in our experience represents the treatment of choice for DFSP occurring on the trunk and extremities.

Lymphangiogenesis-independent resolution of experimental edema.

Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis, and excess VEGF-C has been shown to be ameliorative for edema produced by lymphatic obstruction in experimental models. However, it has recently been shown that edema can resolve in the mouse tail even in the complete absence of capillary lymphangiogenesis when distal lymph fluid crosses the regenerating wound site interstitially. This finding has raised questions about the action of VEGF-C/VEGF receptor (VEGFR) signaling during the resolution of experimental edema. Here, the roles of VEGFR-2 and VEGFR-3 signaling in edema resolution were explored. It was found that edema resolved following neutralization of either VEGFR-2 or VEGFR-3 in the mouse tail skin, which inhibited lymphangiogenesis. Neutralization of either VEGFR-2 or VEGFR-3 reduced angiogenesis at the site of obstruction at day 10 (9.2 +/- 1.2% and 11.5 +/- 1.0% blood capillary coverage, respectively) relative to controls (14.3 +/- 1.5% blood capillary coverage). Combined VEGFR-2/-3 neutralization more strongly inhibited angiogenesis (6.9 +/- 1.5% blood capillary coverage), leading to a reduced wound repair of the lymphatic obstruction and extended edema in the tail skin. In contrast, improved tissue repair of the obstruction site increased edema resolution. Macrophages in the swollen tissue were excluded as contributing factors in the VEGFR-dependent extended edema. These results support a role for VEGFR-2/-3-combined signaling in the resolution of experimental edema that is lymphangiogenesis independent.

Is there a benefit to sentinel lymph node biopsy in patients with T4 melanoma?

BACKGROUND: Controversy exists as to whether patients with thick (Breslow depth>4 mm), clinically lymph node-negative melanoma require sentinel lymph node (SLN) biopsy. The authors examined the impact of SLN biopsy on prognosis and outcome in this patient population. METHODS: A review of the authors' institutional review board-approved melanoma database identified 293 patients with T4 melanoma who underwent surgical excision between 1998 and 2007. Patient demographics, histologic features, and outcome were recorded and analyzed. RESULTS: Of 227 T4 patients who had an SLN biopsy, 107 (47%) were positive. The strongest predictors of a positive SLN included angiolymphatic invasion, satellitosis, or ulceration of the primary tumor. Patients with a T4 melanoma and a negative SLN had a significantly better 5-year distant disease-free survival (DDFS) (85.3% vs 47.8%; P<.0001) and overall survival (OS) (80% vs 47%; P<.0001) compared with those with metastases to the SLN. For SLN-positive patients, only angiolymphatic invasion was a significant predictor of DDFS, with a hazard ratio of 2.29 (P=.007). Ulceration was not significant when examining SLN-positive patients but the most significant factor among SLN-negative patients, with a hazard ratio of 5.78 (P=.02). Increasing Breslow thickness and mitotic rate were also significantly associated with poorer outcome. Patients without ulceration or SLN metastases had an extremely good prognosis, with a 5-year OS>90% and a 5-year DDFS of 95%. CONCLUSIONS: Clinically lymph node-negative T4 melanoma cases should be strongly considered for SLN biopsy, regardless of Breslow depth. SLN lymph node status is the most significant prognostic sign among these patients. T4 patients with a negative SLN have an excellent prognosis in the absence of ulceration and should not be considered candidates for adjuvant high-dose interferon.

Prognostic significance of a positive nonsentinel lymph node in cutaneous melanoma.

PURPOSE: Sentinel lymph node (SLN) biopsy provides important prognostic information for patients with cutaneous melanoma. There may be additional prognostic significance to melanoma spreading from the SLN to nonsentinel lymph nodes (NSLN). We examined the implications of a positive NSLN for overall and distant disease-free survival. METHODS: Using a prospectively maintained, Institutional Review Board-approved melanoma database we studied patients who had a cutaneous melanoma, a positive SLN, and a completion lymph node dissection (CLND). Survival was determined using a combination of hospital records and the Social Security Death Index (SSDI). Univariate and multivariate Cox regression analysis was performed to further characterize predictors of overall and distant disease-free survival. Kaplan-Meier analysis was used to generate survival curves. RESULTS: A total of 429 patients with positive SLN biopsies were identified, with at least one positive NSLN identified in 71 (17%). Median follow-up time was 36.8 months. Presence of a positive NSLN was significantly associated with poor outcome, although long-term survival was possible. Presence of ulceration, high mitotic rate, angiolymphatic invasion, total number of positive nodes, and volume of disease>1% in the SLN were significant predictors of survival on univariate analysis, but lost significance on multivariate. Multivariate Cox analysis revealed several predictors of overall survival: increasing age [hazard ratio (HR) 1.04, P<0.01], Breslow depth (HR 1.76, P<0.01), presence of extracapsular extension in the SLN (HR 2.39, P<0.01), and positive NSLN (HR 1.92, P<0.01). CONCLUSION: Among node-positive melanoma patients, presence of a positive NSLN is a highly significant poor prognostic sign, even after considering the total number of positive nodes and volume of disease in the SLN. CLND after a positive SLN provides this important prognostic information.

Determinants of breast conservation rates: reasons for mastectomy at a comprehensive cancer center.

Bias in referral patterns and variations in multi-disciplinary management may impact breast conservation therapy (BCT) rates between hospitals. Retrospective studies of BCT rates are limited by their inability to differentiate indicated mastectomies versus those chosen by the patient. Our prospective breast cancer data base was queried for patients with invasive breast cancer who underwent surgical therapy at the University of Michigan over a 3-year period. Demographics, stage and histology were recorded along with the reason mastectomy was performed, categorized as "by need" (contraindication to BCT) or "by choice." Multivariate analysis was used to identify factors significantly associated with mastectomy by choice. BCT was associated with tumor size, histology and nodal status, but not older age, either by choice or by need. Of the 34% of patients initially felt to be poor candidates for BCT, it was absolutely contraindicated in 44%, while 56% were thought to have a tumor-to-breast size ratio too large for successful BCT. Of this latter group, 80% underwent neo-adjuvant chemotherapy in an attempt to downstage the primary tumor and perform BCT, which was successful in over half the patients. For the patients initially thought to be good candidates for BCT, only 15% chose to undergo mastectomy, while 5% eventually required mastectomy due to failed attempts to achieve negative margins. Overall, the BCT rate was 63%, however without the use of neo-adjuvant chemotherapy, the BCT rate would have been only 53%. At a tertiary referral center, BCT rates are driven more by contraindications than patient choice, and may be heavily skewed towards mastectomy due to referral patterns. In addition to tumor factors such as stage and histology, BCT rate can be dramatically impacted by neo-adjuvant chemotherapy or genetic counseling. Examining BCT rates alone as a measure of quality, therefore, is not an appropriate standard across institutions serving diverse populations.

Residual disease after re-excision lumpectomy for close margins.

INTRODUCTION: While a positive margin after an attempt at breast conservation therapy (BCT) is a reason for concern, there is more controversy regarding close margins. When re-excisions are performed, there is often no residual disease in the new specimen, calling into question the need for the procedure. We sought to examine the incidence of residual disease after re-excision for close margins and to identify predictive factors that may better select patients for re-excision. METHODS: Our IRB-approved prospective breast cancer database was queried for all breast cancer patients who underwent a re-excision lumpectomy for either close or positive margins after an attempt at BCT. Close margins are defined as < or =2 mm for invasive carcinoma and < or =3 mm for DCIS. Clinicopathologic features were correlated with the presence of residual disease in the re-excision specimen. RESULTS: Three hundred three patients (32%) underwent re-operation for either close (173) or positive (130) margins. Overall, 33% had residual disease identified, 42% of DCIS patients and 29% of patients with invasive disease, nearly identical to patients with positive margins. For patients with DCIS, only younger age was significantly related to residual disease. For patients with invasive cancer, only multifocality was significantly associated with residual disease (OR 3.64 [1.26-10.48]). However, patients without multifocality still had a substantial risk of residual disease. DISCUSSION: The presence of residual disease appears equal between re-excisions for close and positive margins. No subset of patients with either DCIS or invasive cancer could be identified with a substantially lower risk of residual disease.

Axillary staging prior to neoadjuvant chemotherapy for breast cancer: predictors of recurrence.

BACKGROUND: The value of axillary staging prior to delivery of neoadjuvant chemotherapy (NEO) for breast cancer is controversial. Our goal was to analyze the prognostic and therapeutic impact of axillary staging on recurrence. METHODS: The study cohort included 161 patients undergoing comprehensive evaluation by a multidisciplinary approach during the period 1996-2006. Clinicopathologic features were assessed before and after delivery of NEO. Patients with node-positive disease before NEO underwent a post-NEO axillary lymph node dissection at time of definitive breast surgery. RESULTS: At presentation, median age was 49 years; mean tumor size was 45 mm. The axilla was negative in 45 (28.6%) patients. Of the 114 pre-NEO node-positive patients, 65 (57%) were staged histologically. At completion of NEO, partial or complete clinical response was observed in 90.6%; complete pathologic response occurred in 23.6%. Mean residual tumor size was 10.5 mm. Of the 112 initially node-positive patients, 36 (31.6%) had no residual axillary disease post NEO. At median follow-up of 38.1 months, 21.7% patients relapsed. The pre-NEO nodal status was the strongest predictor of treatment failure. A significant risk of distant relapse was based on nodal response to NEO: 8.1% in node-negative patients, 13.9% in the downstaged group, and 22.1% in the persistently positive group (P = 0.047). Delivery of nodal irradiation decreased local recurrence in the downstaged group (12.5% versus 3.7%, P = NS). CONCLUSION: Our experience suggests that comprehensive axillary staging with ultrasound and fine-needle aspiration (FNA) and sentinel lymph node biopsy prior to NEO is both prognostically and therapeutically important in predicting those patients at higher risk of recurrence.

Do micromorphometric features of metastatic deposits within sentinel nodes predict nonsentinel lymph node involvement in melanoma?

INTRODUCTION: Multiple attempts have been made to identify melanoma patients with a positive sentinel lymph node (SLN) who are unlikely to harbor residual disease in the nonsentinel lymph nodes (NSLN). We examined whether the size and location of the metastases within the SLN may help further stratify the risk of additional positive NSLN. METHODS: A review of our Institutional Review Board (IRB)-approved melanoma database was undertaken to identify all SLN positive patients with SLN micromorphometric features. Univariate logistic regression techniques were used to assess potential significant associations. Decision tree analysis was used to identify which features best predicted patients at low risk for harboring additional disease. RESULTS: The likelihood of finding additional disease on completion lymph node dissection was significantly associated with primary location on the head and neck or lower extremity (P = 0.01), Breslow thickness >4 mm (P = 0.001), the presence of angiolymphatic invasion (P < 0.0001), satellitosis (P = 0.004), extranodal extension (P = 0.0002), three or more positive SLN (P = 0.02) and tumor burden within the SLN >1% surface area (P = 0.004). Sex, age, mitotic rate, ulceration, Clark level, histologic subtype, regression, and number of SLN removed had no association with finding a positive NSLN. Location of the metastases (capsular, subcapsular or parenchymal) showed no correlation with a positive NSLN. Decision tree analysis incorporating size of the metastatic burden within the SLN along with Breslow thickness can identify melanoma patients with a positive SLN who have a very low risk of harboring additional disease with the NSLN. CONCLUSION: Size of the metastatic burden within the SLN, measured as a percentage of the surface area, helps stratify the risk of harboring residual disease in the nonsentinel lymph nodes (NSLN), and may allow for selective completion lymphadenectomy.

Sentinel lymph node biopsy for breast cancer: how many nodes are enough?

INTRODUCTION: Sentinel lymph node (SLN) biopsy using blue dye and radioisotope often results in the removal of multiple SLNs. We sought to determine whether there is a point where the surgeon can terminate the procedure without sacrificing accuracy. METHODS: One thousand one hundred ninety-seven patients from University of Michigan and the Mayo Clinic undergoing SLN biopsy formed the study population. Surgeons removed all SLNs until counts within the axilla were less than 10% of the highest node ex vivo and recorded the order in which they were removed. RESULTS: The mean number of SLNs removed per patient was 2.5 (range 1-9). Approximately 42% of patients had three or more lymph nodes removed, while 19% had four or more lymph nodes removed. Eighteen percent of patients (132/725) at University of Michigan and 22% (103/472) at Mayo Clinic had a positive SLN. Ninety-eight percent (231/235) of patients with lymph node metastases were identified by the 3rd SLN while 100% were identified by the 4th SLN. CONCLUSION: Among patients undergoing SLN biopsy for breast cancer, the only positive SLN is rarely identified in the 4th or higher node. Terminating the procedure at the 4th node may lower the cost of the procedure and reduce morbidity.

Inguinal node dissection for melanoma in the era of sentinel lymph node biopsy.

BACKGROUND: With the introduction of sentinel lymph node (SLN) biopsy for melanoma, inguinal lymph node dissections (ILND) are more commonly performed for microscopic disease than for clinically palpable disease. We sought to examine the effect this change has on the morbidity of the operation. METHODS: A retrospective review was performed of all patients who underwent an ILND for melanoma between October 1997 and April, 2006. Clinical and pathologic data were collected and correlated by multivariate analysis with the incidence of a major wound complication. RESULTS: We identified 212 patients, 132 who underwent an ILND for a positive SLN and 80 for clinically palpable disease. Age, sex, and body mass index (BMI) were similar in both groups. Patients with clinically palpable disease had a significantly greater number of involved nodes (3.0 vs 1.96, P = .0013), more often had >or=4 involved nodes (29% vs 9%, P < .001), and a greater incidence of extranodal extension (47% vs 5%, P < .001). Of the 212 patients, 41 (19%) had a significant wound complication. This complication was significantly higher among patients with clinical disease compared to patients with a positive SLN (28% vs 14%, P = .02). Only BMI (odds ratio of 1.1) and the indication for the procedure (odds ratio of 2.2) were independent predictors of a major wound complication. Lymphedema occurred in 30% of the patients and was only significantly associated with clinical disease (41% vs 24%, P = .025). With a median follow-up of 2 years, regional recurrence was not significantly greater in patients with clinically palpable disease (13% vs 9%, P = not significant [ns]), although this result was possibly due to the significantly greater rate of distant recurrence (49% vs 18%, P < .001) and death (48% vs 21%) in these patients. CONCLUSIONS: Patients undergoing an ILND for a positive SLN have a significantly lower risk of postoperative complication or lymphedema than do patients undergoing ILND for clinically palpable disease. There is a benefit in regard to the morbidity of treatment in surgically staging melanoma patients by SLN biopsy and preventing ILND for palpable disease.

Sentinel lymph node biopsy performed after neoadjuvant chemotherapy is accurate in patients with documented node-positive breast cancer at presentation.

BACKGROUND: The optimal strategy for incorporating lymphatic mapping and sentinel lymph node biopsy into the management of breast cancer patients receiving neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node biopsy performed following neoadjuvant chemotherapy have largely reported on patients whose prechemotherapy, pathologic axillary nodal status was unknown. We report findings using a novel comprehensive approach to axillary management of node-positive-patients receiving neoadjuvant chemotherapy. METHODS: We evaluated 54 consecutive breast cancer patients with biopsy-proven axillary nodal metastases at the time of diagnosis that underwent lymphatic mapping with nodal biopsy as well as concomitant axillary lymph node dissection after receiving neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer center between 2001 and 2005. RESULTS: The sentinel node identification rate after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had residual axillary metastases (including eight patients that had undergone resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases (31%) the residual metastatic disease was limited to the sentinel lymph node. The final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three cases (8.6%). The negative final sentinel node accurately identified patients with no residual axillary disease in 17 cases (32%). CONCLUSIONS: Sentinel lymph node biopsy performed after the delivery of neoadjuvant chemotherapy in patients with documented nodal disease at presentation accurately identified cases that may have been downstaged to node-negative status and can spare this subset of patients (32%) from experiencing the morbidity of an axillary dissection.

What is a sentinel node? Re-evaluating the 10% rule for sentinel lymph node biopsy in melanoma.

INTRODUCTION: Many surgeons use the "10% rule" to define whether a lymph node is a sentinel node (SLN) when staging malignant melanoma. However, this increases the number of SLN removed and the time and cost of the procedure. We examined the impact of raising this threshold on the accuracy of the procedure. METHODS: We reviewed the records of 561 patients with melanoma (624 basins) who underwent SLN with technetium Tc99 labeled sulfur colloid using a definition of a SLN as 10% of that of the node with the highest counts per minute (CPM). RESULTS: Of the 624 basins, 154 (25%) were positive for metastases. An average of 1.9 nodes per basin were removed (range 1-6). Metastases were found in the hottest node in 137 cases (89% of positive basins, 97% of basins overall). Increasing the threshold above 10% decreased the number of nodes excised and the costs involved, but incrementally raised the number of false negative cases above baseline (a 4% increase for a "20% rule," 5% for a "30% rule," 6% for a "40% rule," and 7% for a "50% rule"). Taking only the hottest node would raise the false negative rate by 11%. CONCLUSIONS: Although using thresholds higher than 10% for the definition of a SLN will minimize the extent of surgery and decrease the costs associated with the procedure, it will compromise the accuracy of the procedure and is not recommended.

The impact of factors beyond Breslow depth on predicting sentinel lymph node positivity in melanoma.

BACKGROUND: In addition to Breslow depth, the authors previously described how increasing mitotic rate and decreasing age predicted sentinel lymph node (SLN) metastases in patients with melanoma. The objectives of the current study were to verify those previous results and to create a prediction model for the better selection of which patients with melanoma should undergo SLN biopsy. METHODS: The authors reviewed 1130 consecutive patients with melanoma in a prospective database who underwent successful SLN biopsy. After eliminating patients aged <16 years and patients who had melanomas that measured <1 mm, 910 remaining patients were reviewed for clinical and pathologic features and positive SLN status. Univariate association of patient and tumor characteristics with positive SLN status was explored by using standard logistic regression techniques, and the best multivariate model that predicted lymph node metastases was constructed by using a backward stepwise-elimination technique. RESULTS: The characteristics that were associated significantly with lymph node metastasis were angiolymphatic invasion, the absence of regression, increasing mitotic rate, satellitosis, ulceration, increasing Breslow depth, decreasing age, and location (trunk or lower extremity compared with upper extremity or head/neck). Previously reported interactions between mitotic rate and age and between Breslow depth and age were confirmed. The best multivariate model included patient age (linear), angiolymphatic invasion, the number of mitoses (linear), the interaction between patient age and the number of mitoses, Breslow depth (linear), the interaction between patient age and Breslow depth, and primary tumor location. CONCLUSIONS: Younger age, increasing mitotic rate (especially in younger patients), increasing Breslow depth (especially in older patients), angiolymphatic invasion, and trunk or lower extremity location of the primary tumor were associated with a greater likelihood of positive SLN status. The current results support the use of factors beyond Breslow depth to determine the risk of positive SLN status in patients with cutaneous melanoma.

Changes in surgical management resulting from case review at a breast cancer multidisciplinary tumor board.

BACKGROUND: The treatment of breast cancer requires a multidisciplinary approach, and patients are often referred to a multidisciplinary cancer clinic. The purpose of the current study was to evaluate the impact of this approach on the surgical management of breast cancer. METHODS: The medical records of 149 consecutive patients referred to a multidisciplinary breast cancer clinic over a 1-year period with a diagnosis of breast cancer were reviewed retrospectively for alterations in radiologic, pathologic, surgical, and medical interpretations and the effect that these alterations had on recommendations for surgical management. RESULTS: A review of the imaging studies resulted in changes in interpretations in 67 of the 149 patients studied (45%). This resulted in a change in surgical management in 11% of patients. Review of the pathology resulted in changes in the interpretation for 43 of the 149 patients (29%). Thirteen patients (9%) had surgical management changes made solely as a result of pathologic reinterpretation. In 51 patients (34%), a change in surgical management was recommended after discussion with the surgeons, medical oncologists, and radiation oncologists that was not based on reinterpretation of the radiologic or pathologic findings. Overall, a second evaluation of patients referred to a multidisciplinary tumor board led to changes in the recommendations for surgical management in 77 of 149 of those patients studied (52%). CONCLUSIONS: The changes in management stemmed from differences in mammographic interpretation, pathologic interpretation, and evaluation by medical and radiation oncologists and surgical breast specialists. Multidisciplinary review can provide patients with useful additional information when making difficult treatment decisions.

Significance of multiple lymphatic basin drainage in truncal melanoma patients undergoing sentinel lymph node biopsy.

BACKGROUND: Truncal melanoma involving metastases to multiple lymph node basins has a much worse prognosis than tumor involvement of a single lymph node basin. Recent results also suggest that, independently of the status of lymph node involvement, patients with multiple lymphatic basin drainage (MLBD) on lymphoscintigraphy have an increased risk of lymph node metastasis and a worse prognosis than those with a single lymphatic drainage basin. Because published reports have conflicting results, the authors compared their experience at the University of Michigan Comprehensive Cancer Center with recently published findings. METHODS: The authors searched a prospectively maintained melanoma database at the University of Michigan for patients with primary truncal melanoma who underwent lymphoscintigraphy and sentinel lymph node biopsy between 1997 and 2004. The association of MLBD with the clinical and pathologic characteristics collected and the presence of regional metastases was tested by using contingency tables and the chi(2) test statistic and by using the Fisher's exact test statistic when cell frequencies were small. The product-limit method of Kaplan and Meier was used to estimate disease-free and overall survival probabilities. RESULTS: Of 423 patients with primary truncal melanoma who underwent sentinel lymph node biopsy, 123 (29%) had a positive result, and 98 patients (23.2%) had MLBD. Patients with tumors located in the middle of the trunk and tumor ulceration were more likely to have MLBD (P < .0001 and P = .045, respectively). Patients with a single lymphatic drainage basin and MLBD had a similar risk of lymph node metastasis and similar disease-free and overall survival. CONCLUSIONS: Patients with truncal melanomas tend to have MLBD when the tumor is located in the middle of the trunk or when ulceration is present. In our experience, drainage to multiple lymphatic basins was not an independent risk factor for sentinel lymph node metastasis and has no independent prognostic significance.

Impact of estrogen receptor expression and other clinicopathologic features on tamoxifen use in ductal carcinoma in situ.

BACKGROUND: Recent data have demonstrated that benefit from adjuvant tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) is limited to estrogen receptor (ER)-positive lesions. The objective of the current study was to correlate clinicopathologic features of DCIS with ER expression and the impact of this information on tamoxifen counseling. METHODS: Women with DCIS who were treated from 2001 to 2004 were evaluated. Routine ER staining was initiated in January 2003. RESULTS: Ninety-four women (mean age, 57.6 years) were analyzed. The mean DCIS size was 0.98 cm. ER-staining was performed in 55 lesions, and 76% were ER-positive. All Grade 1 and 2 DCIS lesions were ER-positive, compared with 54% of high-grade lesions (P<.001); no other clinicopathologic feature significantly predicted ER status. Overall, 58 patients (62%) were offered tamoxifen, and the rates were similar for the pre-ER and post-ER staining periods. In the pre-ER staining period, surgical treatment and grade were associated with offering tamoxifen (75% of patients who underwent breast conservation vs. 40% of patients who underwent mastectomy; P = .03; 78% of patients with Grade 1 or 2 lesions vs. 45% of patients with Grade 3 lesions; P = .04). In the post-ER staining period, however, only ER status was correlated significantly with offering tamoxifen (71% of patients with ER-positive lesions vs. 31% of patients with ER-negative lesions; P = .01). Approximately 66% of patients who were offered tamoxifen agreed to treatment (approximately 33% of the total DCIS study sample). No clinicopathologic features predicted for tamoxifen acceptance by patients in either the pre-ER or post-ER staining periods. CONCLUSIONS: Seventy-five percent of DCIS lesions were ER-positive. ER staining significantly influenced the likelihood that clinicians would offer tamoxifen to patients with DCIS, but it had no impact on whether patients accepted treatment.

Does the method of biopsy affect the incidence of sentinel lymph node metastases?

More detailed examination of the sentinel lymph node (SLN) in breast cancer has raised concerns about the clinical significance of micrometastases, specifically isolated tumor cells detected only through immunohistochemical (IHC) staining. It has been suggested that these cells do not carry the same biologic implications as true metastatic foci and may represent artifact. A retrospective institutional review board-approved review was conducted on clinically node-negative breast cancer patients who underwent SLN biopsy (SLNB) between 1997 and 2003. Retrospective analysis of tumor characteristics and the method of the initial diagnostic biopsy were correlated with the presence and nature of metastatic disease in the SLN. Of 537 SLNBs, 123 (23%) were hematoxylin-eosin (H&E) positive. SLN positivity strongly correlated with tumor size (p<0.001) and tumor grade (p=0.025), but not with the method of biopsy (needle versus excisional biopsy). Prior to July 2002, we routinely evaluated H&E-negative SLNs with IHC (n=381). Of the 291 H&E-negative patients, 26 had IHC-only detected micrometastases (9%). The likelihood of detecting IHC-only metastases did not correlate with tumor size or grade, but was significantly higher in patients undergoing excisional biopsy than core needle biopsy. While the method of biopsy has no demonstrable effect on the likelihood of finding metastases in the SLN by routine serial sectioning and H&E staining, it may significantly impact the likelihood of finding micrometastases by IHC. IHC should not be used routinely in the evaluation of the SLN and caution should be used when basing treatment decisions (completion axillary lymph node dissection or adjuvant therapy) on IHC-only detected micrometastases.