Lymphoepithelioma-Like Carcinoma of the Breast: A Case Report of a Rare Type of Invasive Carcinoma.

Lymphoepithelioma carcinoma (LELC) is an extremely rare type of mammary cancer. Based on the histology, it can be misdiagnosed with inflammatory lesions like mastitis and medullary carcinoma or other hematopoietic neoplasms like lymphoma in the breast. Since LELC has a good response to chemotherapy with a good prognosis, t is prognostically important to recognize LELC. We report a rare case of LELC in a 51-year-old pre-menopausal female with a left breast mass, diagnosed with invasive ductal carcinoma (IDC), LELC type, treated with mastectomy, followed by adjuvant chemotherapy and radiotherapy, with a disease-free interval of 10 months. Herein, we present the case with its clinical presentation, radiologic imaging, histopathological features, and immunohistochemistry (IHC) findings. The rarity of this type of breast tumor warrants studying the behavior of these uncommon tumors to avoid misdiagnosis and establish well-defined criteria for diagnosis.

Nipple Adenoma: A Benign Disease With a Suspicious Presentation.

Nipple adenoma is a rare proliferative lesion that originates from the lactiferous ducts of the nipple. Though it is benign, the typical presentation includes suspicious symptoms-a firm nodule, crusting erosion, and/or discharge from the nipple. These findings can raise concern for malignancy and in particular, Paget's disease. We report two cases of this uncommon entity, highlighting the variable clinical presentation and keys to the diagnostic evaluation and management.

A surprising complication of breast augmentation surgery.

Infections caused by opportunistic fungal organisms such as Scedosporium spp. have been increasingly recognized over the last few decades. Most affected patients are immunocompromised or critically ill, but Scedosporium spp. infections have also been described in immunocompetent patients, such as localized disease from direct inoculation or in near-drowning events. We describe a case of a patient with no known underlying immune impairment who experienced significant infection with Scedosporium apiospermum at both sites of breast augmentation. Once identified, the choice of therapeutics can be challenging given the intrinsic resistance and variable activity of different antifungal agents; however, other factors also impact the outcome of this infection such as the host immune status. Thus, both the recognition and treatment of Scedosporium infections can be challenging.

Squamous Cell Carcinoma Arising in Breast Implant Capsules.

ABSTRACT: Breast augmentation and reconstruction utilizing implants are among the most common plastic surgery procedures performed in the United States. A small proportion of these implants are removed each year. We report 2 cases where routine pathologic evaluation of capsulectomy specimens revealed squamous cell carcinoma associated with the breast implant capsule and discuss the possible pathogenesis of this unusual entity. Both patients had long-standing implants (>10 years) and presented with acute unilateral breast erythema and swelling. Intraoperatively, the capsules for both cases appeared thickened and calcified, containing extensive granulomatosis and keratinaceous debris invading into the chest wall. Extensive workup failed to find an occult primary. One patient died from a malignant pleural effusion secondary to tumor invasion during chemotherapy, and the second patient obtained stabilization of the mass after 5 weeks of chemotherapy but subsequently declined further surgical intervention. A thorough literature review was performed, and 5 similar reports were identified, involving 6 patients. All patients presented with similar clinical presentations as ours and had poor outcomes. The mean reporting age at diagnosis was 60 years, and the average time from initial implant to diagnosis was 25 years. Due to the small numbers of squamous cell carcinomas associated with breast implant capsules, the true association between the 2 is unknown. It is postulated that chronic inflammation/irritation from the breast implant and epithelialization of the capsule play a significant role in the disease process. This may represent a new entity of "chronic inflammatory capsular malignancies." Increased awareness of this entity may allow for earlier suspicion, diagnosis, and management.

Can Oncotype DX testing be omitted in invasive breast cancer patients with clinicopathologic factors predicting very high pretest probability of a concordant result?

OBJECTIVE: To determine if clinicopathologic (CP) factors could identify patients at "very low" and/or "very high" pretest probability of a high Oncotype DX (ODX) score. METHODS: A retrospective analysis of all patients that had ODX testing 2008-2018 at a single institution. RESULTS: Of 215 patients, all 16 (7.4%) with "all high" risk CP factors had high ODX scores, and all 45 (20.9%) over age 50 with "all low" risk CP factors had ODX recommendations for no chemotherapy. CONCLUSIONS: Oncotype DX results did not change chemotherapy recommendations in those with "very low" or "very high" pretest probability of high ODX scores.

Diagnostic Delays in Metastatic Amelanotic Melanoma Presenting as Breast Pain.

BACKGROUND Breast metastases from melanoma are rare. Amelanotic melanoma is difficult to diagnose, as primary lesions not only lack the pigment typical of melanoma, but also lack other features associated with these tumors, including asymmetry, irregular borders, and color variegation. CASE REPORT A 58-year-old woman presented with an enlarging mass on her left breast, a finding confirmed by physical examination. Mammography showed a 10-cm breast mass of category 4 according to the Breast Imaging Reporting and Data System (BI-RADS). Staging computed tomography (CT) showed widely scattered metastatic sites in the brain, lungs, mediastinum, and adrenal glands. A biopsy of the mass in her left breast was non-diagnostic due to extensive necrosis. Because of severe pain, simple left breast mastectomy was performed. Tissue from the mastectomy revealed a diagnosis of amelanotic malignant melanoma. CONCLUSIONS Diagnosing amelanotic melanoma is difficult without tissue biopsy as these tumors lack the typical features of melanoma and can mimic other dermatologic diseases. This frequently results in a significant delay in diagnosing amelanotic melanoma, with patients often presenting with advanced stage disease having poor prognosis.

A new era of neoadjuvant treatment with Pertuzumab: Should the 10-lymph node guideline for axillary lymph node dissection in breast cancer be revised?

BACKGROUND: Pertuzumab has improved pathologic complete response rates when compared with other chemotherapeutics in the treatment of HER-2 positive breast cancer patients. AIMS: We sought to determine if axillary lymph node dissections (ALNDs) yielding at least the national standard of 10 lymph nodes is lower in patients who received neoadjuvant pertuzumab. METHODS AND RESULTS: A retrospective database identified patients who underwent ALND for breast cancer. We compared the axillary lymph node retrieval rates in those who received or did not receive neoadjuvant pertuzumab. Of 139 breast cancer patients who underwent ALND, fewer than 10 axillary lymph nodes were found in 41.7% of patients who received neoadjuvant pertuzumab (P < 0.01) and 18.6% of patients who received neoadjuvant therapy without pertuzumab (P = 0.01). CONCLUSION: Neoadjuvant chemotherapy was associated with a significantly lower rate of "adequate" ALNDs as defined by current guidelines. The patient subset that received neoadjuvant pertuzumab was more likely to have fewer than 10 axillary lymph nodes retrieved.

Excisional biopsy of borderline lesions after large bore vacuum-assisted core needle biopsy- is it necessary?

The current recommendation for borderline breast lesions after core needle biopsy is for surgical excision due to a high rate of pathologic underestimation. With the use of vacuum-assisted core needle (VACN) biopsy devices, upgrade rates have improved, but still average 20 per cent. We routinely use larger bore VACNs (7- and 8-gauge) than previously reported (9 to 11-gauge). The aim of this study is to evaluate the upgrade rate to malignancy in patients undergoing VACN using larger bore needles. VACN biopsies were performed in 902 patients. Of those, 87 were recommended excisional biopsy for borderline or noncorrelating lesions and 66 underwent the procedure. Two patients were upgraded to cancer, for an overall upstage rate of 3 per cent. Both of these underestimations were in patients that initially had atypical ductal hyperplasia. In the patients not excised, no patient developed further cancer. A 7- or 8-gauge needle was used in 57 per cent of patients, greater than 90 per cent removal of the initial lesion was accomplished in 53 per cent of cases, and there were no bleeding complications. This study suggests that upgrade rates decline with larger bore biopsy needles with near complete excision of the initial lesion, and that some borderline lesions may potentially be managed nonoperatively.

Fluorescence in situ hybridization and K-ras analyses improve diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses.

OBJECTIVES: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is the main diagnostic modality for pancreatic mass lesions. However, cytology is often indeterminate, leading to repeat FNAs and delay in care. Here, we evaluate whether combining routine cytology with fluorescence in situ hybridization (FISH) and K-ras/p53 analyses improves diagnostic yield of pancreatic EUS-FNA. METHODS: Fifty EUS-FNAs of pancreatic masses in 46 patients were retrospectively analyzed. Mean follow-up was 68 months. Thirteen initial cytologic samples (26%) were benign, 23 malignant (46%), and 14 atypical (28%). We performed FISH for p16, p53, LPL, c-Myc, MALT1, topoisomerase 2/human epidermal growth factor receptor 2, and EGFR, as well as K-ras/p53 mutational analyses. RESULTS: On final diagnosis, 11 (79%) of atypical FNAs were malignant, and 3 benign (21%). Fluorescence in situ hybridization was negative in all benign and all atypical samples with final benign diagnosis. Fluorescence in situ hybridization plus K-ras analysis correctly identified 60% of atypical FNAs with final malignant diagnosis. Combination of routine cytology with positive FISH and K-ras analyses yielded 87.9% sensitivity, 93.8% specificity, 96.7% positive predictive value, 78.9% negative predictive value, and 89.8% accuracy. CONCLUSIONS: Combining routine cytology with FISH and K-ras analyses improves diagnostic yield of EUS-FNA of solid pancreatic masses. We propose to include these ancillary tests in the workup of atypical cytology from pancreatic EUS-FNA.

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy.

AIM: To investigate whether tumor marker staining can improve the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to diagnose pancreatic malignancy. METHODS: Patients who underwent EUS-FNA were retrospectively identified. Each EUS-FNA specimen was evaluated by routine cytology and stained for tumor markers p53, Ki-67, carcinoembryonic antigen (CEA) and CA19-9. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were calculated in order to evaluate the performance of each test to detect malignancy. RESULTS: Sixty-one specimens had complete sets of stains, yielding 49 and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions due to pancreatitis, respectively. Cytology alone had sensitivity and specificity of 41% and 100% to detect malignancy, respectively. In 46% of the specimens, routine cytology alone was deemed indeterminate. The addition of either p53 or Ki-67 increased the sensitivity to 51% and 53%, respectively, with perfect specificity, PPV and PLR (100%, 100% and infinite). Both stains in combination increased the sensitivity to 57%. While additional staining with CEA and CA19-9 further increased the sensitivity to 86%, the specificity, PPV and PLR were significantly reduced (at minimum 42%, 84% and 1, respectively). Markers in all combinations performed poorly as a negative test (NPV 26% to 47%, and NLR 0.27 and 0.70). CONCLUSION: Immunohistochemical staining for p53 and Ki-67 can improve the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.

The role of fluorescence in situ hybridization assay for surveillance of non-muscle invasive bladder cancer.

OBJECTIVE: To compare the sensitivity and specificity of UroVysion fluorescence in situ hybridization assay (FISH) with cystoscopy and urine cytology in the surveillance of patients with documented non-muscle invasive bladder cancer (CIS, pTa and pT1). METHODS: This retrospective study was done on a consecutive series of patients undergoing surveillance for non-muscle invasive bladder cancer. The results of FISH were analyzed with concurrent cystoscopy and urine cytology. RESULTS: In all, 94 follow up visits from 59 patients were evaluated. The mean follow up was 52 months. FISH detected 30/48 recurrences of bladder cancer, as compared to 20/48 for cytology and 47/48 on cystoscopy. Hence, the sensitivity of FISH was 63% compared to 42% for cytology (p value 0.03) and 98% for cystoscopy (p value 0.0001). However, cytology was significantly more specific (89%) than FISH (65%) or cystoscopy (41%). FISH was significantly more sensitive in diagnosing Grade 3 tumors (p = 0.0005) than Grades 1 and 2 tumors, when compared with cytology. There was no significant difference in the sensitivity and specificity between FISH and cytology for Grade 1 and 2 tumors. Sensitivity of urine cytology was similar for Grade 3 versus Grades 1 and 2 tumors (p = 0.56). FISH was able to detect all three CIS recurrences whereas cytology was positive in two and atypical in one sample. CONCLUSIONS: FISH has a significantly higher sensitivity than cytology in diagnosing patients with Grade 3 bladder tumors. The low specificity of FISH seen in our study and based on the currently available evidence, the test does not satisfy the criteria for replacing cystoscopy or cytology for surveillance of patients with non-muscle invasive bladder cancer.

Evolution of fine needle aspiration cytology in the accurate diagnosis of pancreatic neoplasms.

In the era of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), a minimally invasive, safe, and accurate cytologic examination of a variety of intra-abdominal neoplasms has become possible. To assess the efficacy of EUS-FNA for diagnosis of primary pancreatic tumors, a 10-year retrospective review of a consecutive series of patients diagnosed between 1996 and 2005 was undertaken. Comparisons were made between early (1996-2000) and late (2001-2005) periods regarding diagnostic modalities used and the concordance of EUS-FNA cytology with macroscopic tissue histology. Although macroscopic biopsy diagnostic yield did not change over time, yield from EUS-FNA increased from 40 per cent to 95 per cent (P = 0.001). Because of improved accuracy of FNA cytology, only six per cent of tumors required additional macroscopic tissue histology in the late period versus 35 per cent in the early period (P = 0.001). There was 100 per cent concordance between the cytologic and histologic diagnoses in the late period versus only 33 per cent in the early period (P = 0.032). We conclude that (1) the frequency of pathologically diagnosed pancreatic tumors doubled over 10 years, (2) utilization of EUS-FNA significantly increased the accuracy of cytologic diagnosis, and (3) as a result, the need for macroscopic tissue biopsy for diagnosis of pancreatic neoplasms has been obviated.

Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of pancreas.

Solid pseudopapillary tumor of pancreas (SPT) is a rare neoplasm that occurs most often in young females with the two distinct features, the 'solid-cystic' gross appearance, and the 'solid-pseudopapillary' microscopic pattern. It has been reported that almost all SPT tumors contain a mutation in the beta-catenin gene; however, the histogenetic origin of this tumor remains largely a mystery. E-cadherin is a cell adhesion molecule that links to catenins to form cell adhesion junctions, which is associated with the cytoskeleton formation. In this study, we examined the expression of E-cadherin and beta-catenin from SPT in an attempt to determine the molecular basis for the unusual morphology of this tumor. Nine cases of SPT were retrieved from Surgical Pathologic Archives of three institutions, including one male and eight females. H&E slides of each case were reviewed to confirm the diagnosis. The beta-catenin gene was sequenced in one case. E-cadherin and beta-catenin immunostains, were performed on all nine cases. Sequencing analysis on one case showed a point mutation of the beta-catenin gene, confirming previous findings that almost all SPT tumors contain mutation in the beta-catenin gene. Immunostains showed that, in both solid and pseudopapillary areas, all the tumor cells lost expression of E-cadherin, and beta-catenin nuclear expression was observed in all cases. Our findings suggest that loss of cytoplasmic beta-catenin protein in the cell adhesion complex due to beta-catenin gene mutation, results in instability of the complex, loss of E-cadherin in cell membrane, and eventually dissociation of the tumor cells to form the pseudopapillary pattern.

Outcomes of surgical and sonographic assessment of breast masses in women younger than 30.

Assessment of breast masses in young women is challenging due to normal glandular variance. Our purpose is to define the outcomes of specialized physical exam, selective breast sonography (BUS), and biopsy in women younger than 30. Five hundred forty-two patients younger than 30 referred with a palpable breast mass were studied. Patients' mean age was 24.8. Surgeon's physical exam confirmed a dominant mass in 44 per cent of cases. Thirty-seven per cent had normal clinical exams. Median tumor size was 2.2 cm. On multivariate analysis, a mass on surgeon's clinical exam (P < 0.0001), and BUS (P = 0.0001) predicted the presence of a true mass. Fifty-three per cent of self-detected abnormalities were true masses compared to 18 per cent when detected by the primary care provider (PCP) (P < 0.001). Most common diagnoses were fibroadenoma (72%), breast cysts (4%), or fibrocystic changes (3%). Malignancy occurred in 1 per cent. In summary, breast mass is a common reason for surgical consultation. Normal glandular nodularity is often mistaken for a mass. However, a judicious approach of physical exam by a surgeon using selective BUS and image guided core biopsy provides an efficient and safe approach for diagnosis. Breast malignancy is a rare but serious cause of breast mass in young women.

Diagnosis of palpable breast masses: ultrasound-guided large core biopsy in a multidisciplinary setting.

Cytologic diagnosis of palpable breast masses is an accepted method for diagnosis. However, the high nondiagnostic rate causes repeat biopsy, unnecessary delays, and increased costs. Our purpose is to evaluate the use of ultrasound (US)-guided large-core needle biopsy as part of the minimally invasive multidisciplinary diagnosis of palpable breast masses. We studied 502 consecutive patients with 510 palpable solid breast masses seen and evaluated by a multidisciplinary team. Patients had US-guided core biopsy. Clinical-imaging-pathologic correlation (CIPC) was done in all cases. Core biopsy was deemed conclusive if CIPC was congruent and was used to guide definitive management. The median age of our patients was 39 years. Median tumor size was 2.2 cm. Of these cases, 463 (91%) had a conclusive diagnosis on CIPC. Core needle findings on 47 masses were nondefinitive to guide therapy (fibroepithelial lesion, atypical ductal hyperplasia, intraductal papilloma, CIPC). Three cancers were detected in this group on excisional biopsy. In conclusion, US-guided large-core needle biopsy is a sensitive method for diagnosis of palpable breast masses. Multidisciplinary correlation of clinical findings, imaging, and pathology is essential for success. This approach improves use of operating room resources and maximizes patient participation in the decision-making process.

Sentinel lymph node mapping of breast cancer: a case-control study of methylene blue tracer compared to isosulfan blue.

Isosulfan blue has been traditionally used as a tracer to map the lymphatic system during identification of the sentinel lymph node. However, allergic reactions may be life threatening. We compared the efficacy of methylene blue dye as a tracer for sentinel lymph node biopsy to isosulfan blue dye. In an analysis of 164 cases, there was no clinical or statistically significant difference in the success rate of sentinel node biopsy (P = 0.22), the number of blue sentinel nodes harvested (P = 0.46), the concordance with radioactive sentinel nodes (P = 0.92), or the incidence of metastases (P = 0.87) when methylene blue tracer was compared to isosulfan blue. No adverse reaction to either blue dye was observed. In conclusion, intraparenchymal injection of methylene blue dye is a reliable tracer for the lymphatic system and nodal identification during sentinel node mapping for breast cancer. It is safe, inexpensive, and readily available.

Focused microwave phased array thermotherapy for ablation of early-stage breast cancer: results of thermal dose escalation.

BACKGROUND: Tumor ablation as a means of treating breast cancer is being investigated. Microwave energy is promising because it can preferentially heat high-water-content breast carcinomas, compared to adipose and glandular tissues. METHODS: This is a prospective, multicenter, nonrandomized dose-escalation study of microwave treatment. Thermal dose was measured as (1) thermal equivalent minutes (cumulative equivalent minutes; CEM) of treatment relative to a temperature of 43 degrees C and (2) peak tumor temperature. Microwaves were guided by an antenna-temperature sensor placed percutaneously into the tumor. Outcomes measured were pathologic response (tumor necrosis) side effects. RESULTS: Twenty-five patients (mean age, 57 years) were enrolled. The mean tumor diameter was 1.8 cm. Tumoricidal temperatures (>43 degrees C) were reached in 23 patients (92%). Tumor size was unchanged after thermotherapy (P = not significant). Pathologic necrosis was achieved in 17 (68%) patients. Complete necrosis of the invasive component was achieved in two patients. One hundred forty CEM is predictive of a 50% tumor response, and 210 CEM is predictive of a 100% tumor response (P =.003). Univariate linear regression predicts that peak tumor temperatures of 47.4 degrees C and 49.7 degrees C cause a 50% tumor response and a 100% tumor response, respectively. CONCLUSIONS: Thermotherapy causes tumor necrosis and can be performed safely with minimal morbidity. The degree of tumor necrosis is a function of the thermal dose. Future studies will evaluate the impact of high doses of thermotherapy on margin status and complete tumor ablation.

Lymphatic tumor burden negatively impacts the ability to detect the sentinel lymph node in breast cancer.

Sentinel lymph node (SLN) biopsy is the preferred method of nodal breast cancer staging. Techniques of SLN biopsy rely on transport of interstitial molecules through mammary lymphatics. Lymphatic flow may be disrupted by tumor emboli. Increased lymphatic tumor burden may be responsible for failure to identify the sentinel lymph node in patients with breast cancer. A prospective database of 110 patients who had SLN biopsy between January 2001 and December 2002 was analyzed. The number of metastatic axillary lymph nodes was used as a measure of lymphatic tumor burden. SLN was found in 94 per cent of cases. It was not found in seven patients; five of them had extensive axillary metastases (71%) compared to 23 per cent when SLN was found (P = 0.001). The average number of metastatic lymph nodes was larger when SLN was not found compared to when SLN was found (12.8 vs. 3.9, respectively, P = 0.002). Increasing numbers of metastatic nodes correlated with decreasing success in SLN biopsy (P = 0.075). The incidence of axillary metastases is higher in patients in whom the sentinel node is not found. High lymphatic tumor burden may have a causative role in SLN biopsy technical failure. Axillary dissection should be performed if SLN is not found, regardless of the tumor size or histology.