Subsequent Excisional Biopsy Research Articles

Correlation of maximum breast carcinoma dimension on needle core biopsy and subsequent excisional biopsy: A retrospective study of 50 non-palpable imaging-detected cases

AimsThere are scant data on the correlation of maximum tumor dimension (MTD) in needle core biopsy (NCB) and in subsequent excisional biopsy (EXB) with various pre-NCB imaging studies (VIS)-especially in the context of screen-detected invasive carcinoma (SIC). Methods and resultsRetrospectively studied were consecutive (2012–2013) non-palpable, SIC diagnosed on NCB with subsequent EXB. Data on MTD on VIS (either mammogram, or ultrasound, or MRI), NCB and EXC were analyzed. Mean MTD on VIS was 12.5mm (range: 0–45mm). Mean MTD on NCB was 6.7mm (range: 1–15mm). Mean residual MTD on EXB was 12.9mm (range: 0–40mm). Mean number of NCB performed per SIC was 5 (range: 1–13). Overall, 81% of all NCB were involved by SIC. The difference between MTD at EXC and VIS was statistically not significant (p>0.05). Spearman correlation coefficient for MTD on VIS and EXC was r=0.8718 (p<0.0001) showing a significant correlation. The mean tissue volume procured on NCB-calculated by using Aperio whole slide scanning and NIH Image J image analysis was 95.5mm3 (range: 4.3–887.5mm3, median: 23mm3). A Bland–Altman plot showed that MTD of ≥7mm on EXB is a useful cut-off point predictive of (any) increase in MTD at EXB. Six of the 13 patients with MTD<7mm on EXB showed a decrease in size; while no patient with MTD on EXB that was ≥7mm showed any decrease in size. (Fisher's exact test, P=0.001, two-tailed). Overall 88% (44 out of 50 patients) of SIC showed no decrease in MTD on EXB, with an increase by ≥4mm in size (sufficient to upstage “T”) in MTD of ≥7mm on EXB in 75.6% (28 of 37 patients with MTD of ≥7mm on EXB). 20.8% of SIC (5 of 24 patients) that were <7mm on NCB (with a mean combined Nottingham grade score of 5 {r: 4–6} showed decrease in MTD at EXB. ConclusionsIn this pilot study of SIC, (i) MTD on VIS was predictive of MTD on EXB, (ii) MTD of ≥7mm on NCB was predictive of an increased MTD on EXB in most cases, with potential for “upstaging” tumors, and (iii) MTD of <7mm on NCB was predictive of decreased MTD on EXB in 20.8% of (mostly grade I) SIC. Procured tissue volume on NCB contributed to decrease in MTD on EXB in small, low-grade carcinomas.

Pure Signet-ring Cell Carcinoma of Lung by Fine Needle Aspiration in a Smoking Asian American: Case Report and Literature Review

Pure primary Signet-Ring Cell Carcinoma (SRCC) of lung is an extremely rare entity. Typically seen in nonsmokers, it is considered to be highly invasive, highly aggressive and carries a worse prognosis when compared to other types of lung tumors. Cytological identification of pulmonary SRCC is challenging and must be differentiated from both benign and malignant lesions. Here we describe a case of a 40-year-old immigrant Chinese male with a significant past medical history of smoking, who was found to have 2.7 cm lung nodule on CT scan. A subsequent CT scan two weeks later showed the original right lung nodule with no evidence of extra pulmonary lesions on the PET scan and the bone scan. Bronchoalveolar lavage and brushings, as well as fine needle aspiration, of the lung lesion revealed an adenocarcinoma with 100% signet ring cell morphology. Due to the lack of extra pulmonary malignancy according to radiographic evidence, the following immunocytochemistry work up on the cell block was performed in order to characterize the lesion as primary pulmonary SRCC: CK7, CK20, TTF-1, p63, CDX2, thyroglobulin, CD68, napsin A, PSA and PSAP. Subsequent excision biopsy was obtained, which revealed adenocarcinoma with 95% signet ring cell purity.

Congenital Malignant Melanoma

Although rare, congenital malignant melanoma (CMM) should be considered in the differential diagnosis of congenital skin lesions. We report a case of CMM in a 4-month-old infant presenting with an enlarging scalp mass, initially thought to be a hemangioma. Incisional biopsy of the lesion showed a compound congenital nevus with atypical cells suggestive of a proliferative nodule versus malignancy on histopathology. Subsequent excisional biopsy revealed malignant melanoma, and further workup confirmed extensive disease with distant metastases. Cytogenetic analysis of both the tumor sites showed highly abnormal karyotypes including pseudotetraploidy, telomere associations, and evidence of gene amplification, all consistent with malignancy. Fluorescence in situ hybridization demonstrated amplification of the MYC gene, with no copy number changes in CDKN2A (INK4/ARF), PTEN, or Cyclin D1. Our report details the cytogenetic and molecular studies of CMM, which provide insight into the biologic behavior of the lesions and may confirm diagnosis when histopathology is not determinant.

Flat Ductal Intraepithelial Neoplasia 1A Diagnosed at Stereotactic Core Needle Biopsy: Is Excisional Biopsy Indicated?

This study correlates ductal intraepithelial neoplasia (DIN) 1A diagnosed at stereotactic spring core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) with the subsequent surgical histologic results or long-term follow-up imaging findings to predict the likelihood of upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma. Stereotactic imaging-guided CNBs and VABs were performed principally for assessment of microcalcifications seen on mammography. DIN 1A diagnoses made at CNB or VAB were correlated with subsequent excisional biopsy results or imaging follow-up. Patients were included only if there was no concomitant CNB or VAB diagnosis of DIN 1B, atypical lobular hyperplasia, lobular carcinoma in situ or DCIS, papillary lesion, or invasive carcinoma. Surgical biopsy results were obtained for 239 patients. Upgrade was defined as a diagnosis of DCIS or invasive carcinoma at surgery. Patients who did not undergo surgical excision were followed with imaging. An upgrade rate of 4.2% (10 lesions in 239 patients) is reported. The remaining samples (229/239) had a surgical diagnosis of DIN 1A or DIN 1B, lobular carcinoma in situ, or a benign finding with no atypia. The upgrade rate of DIN 1A diagnosed at CNB or VAB was 4.2%. These results indicate it may be reasonable to avert immediate surgery in favor of short-term imaging follow-up.

Two Cases of Supraclavicular Lymph Node Metastasis in Pancreatic Adenocarcinoma

The supraclavicular lymph node (SCN) is frequently involved in lymphoma and metastatic malignancies of the breast and lung, but is extremely rarely involved in pancreatic cancer. Only 10 such cases have been reported in the medical literature worldwide. We herein report an additional two cases. An 83-year-old male patient had a 7.6 × 5 cm pancreatic tumor from the pancreatic head to tail, and a 71-year-old male patient had a 2.8 × 1.9 cm pancreatic body tumor. PET-CT revealed SCN metastasis, and subsequent excisional biopsy confirmed metastatic adenocarcinoma. With the more popular use of PET-CT in patients with pancreatic cancer, the number of cases of metastasis to the SCN is expected to increase. This suggests that lymphatic spread is the main metastatic route in pancreatic cancer. Further large-scale studies along with increased numbers of case reports are needed to determine whether lymphatic spread is the main metastatic route in pancreatic cancer. (Korean J Med 2013;85:77-82)

Excision biopsy in a patient with suspected local anaesthetic allergy: use of 0.9% saline with benzyl alcohol as local anaesthesia

Dermatologists may see patients with actual or suspected local anaesthetic (LA) allergy who require an urgent dermatological procedure to be performed without time for formal allergy testing. We report a case of shave biopsy and subsequent excision biopsy of an atypical naevus performed using tumescent analgesia with 0.9% saline containing benzyl alcohol preservative. The tumescence itself and the benzyl alcohol present in the 0.9% saline solution provided sufficient analgesia for excision. This technique may be an option for managing urgent procedures in patients suspected or known to have allergy to LA.

Flat epithelial atypia with and without atypical ductal hyperplasia: to re-excise or not. Results of a 5-year prospective study

Flat epithelial atypia (FEA) of the breast have a tendency to calcify and, as such, are becoming increasingly detected by mammography. There is no consensus yet on whether to excise these lesions or not after diagnosis on core needle biopsies (CNB). We reviewed 3,948 cases of breast CNB between June 2004 and June 2009 correlating histomorphologic, radiological, and clinical features. There were 3.7 % (145/3,948) pure FEA and 1.5 % (58/3,948) concomitant FEA and atypical ductal hyperplasia (ADH). In the pure FEA population, 46.2 % (67/145) had microcalcifications on mammography with 65.5 % (95/145) of patients undergoing subsequent excisional biopsies with the following findings: benign 20 % (19/95), ADH 37.9 % (36/95), ductal carcinoma in situ (DCIS) 1.1 % (1/95), and DCIS and invasive ductal carcinoma (IDC) 2.1 % (2/95). In the concomitant FEA and ADH group, 86.2 % (50/58) patients had microcalcifications on radiograph with 74.1 % (43/58) of patients undergoing subsequent excisions with: benign 23.3 % (10/43), DCIS 9.3 % (4/43), DCIS and IDC 4.7 % (2/43), DCIS + lobular carcinoma in situ + invasive lobular carcinoma 2.3 % (1/43), and tubular carcinoma 2.3 % (1/43). The incidence of carcinoma in the FEA + ADH group is 18.6 % (8/43) and 3.2 % (3/95) for the pure FEA group. This difference is statistically significant (p = 0.0016). The relative risk of carcinoma in the ADH + FEA group versus the pure FEA group is 6.4773, with 95 % CI of 1.8432 and 22.76 24. Five-year mean follow-up in the unexcised pure FEA did not show any malignancies. These findings suggest that pure FEA has a very low association with carcinoma, and these patients may benefit from close clinical and mammographic follow-up while the combined pure FEA and ADH cases may be re-excised.

Silicone lymphadenopathy: an unexpected cause of neck lumps

To report a rare case of silicone lymphadenopathy solely affecting the left supraclavicular lymph nodes. Our patient presented with a painless swelling in the left supraclavicular region. Notably, she had previously undergone cosmetic breast augmentation using silicone-containing implants. Radiological imaging and subsequent excisional biopsy of the swelling produced findings consistent with a silicone foreign body reaction secondary to bilateral breast implant rupture. Silicone lymphadenopathy following breast augmentation primarily affects the axillary nodes. Supraclavicular lymph node involvement is unusual. To our knowledge, this is the first report in the English language literature of silicone lymphadenopathy manifesting solely in the supraclavicular lymph nodes. Although the need to exclude malignancy in such cases is of the utmost importance, silicone lymphadenopathy should also be considered in the differential diagnosis. Fine needle aspiration cytology is a useful initial investigation, which may be followed up by excisional biopsy and histological analysis for further confirmatory diagnostic information.

Concurrent CD5-negative small lymphocytic lymphoma (SLL) and CD5-positive metastatic carcinoma of unknown primary in a lymph node biopsy

CD5 expression is considered a key marker for the diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We report an unusual case of CD5-negative (CD5−) SLL with a concurrent CD5-positive (CD5+) adenocarcinoma of unknown primary involving the same lymph node. An 83-year-old woman with a history of CD5− B cell lymphoma diagnosed on a core biopsy of a cervical lymph node presented with jaundice and was found to have a 2.5-cm pancreatic mass. A fine needle aspiration of the mass revealed a CD5− monotypic B cell population. A subsequent excisional biopsy of a cervical lymph node showed morphologic findings typical for SLL, including the presence of multiple proliferation centers. However, the neoplastic lymphocytes were negative for CD5 by both flow cytometric analysis and immunohistochemistry. Interestingly, multifocal metastatic adenocarcinoma was identified and was positive for CD5. Lack of CD5 expression often leads to the exclusion of CLL/SLL, particularly in small biopsy samples. However, rare cases of CD5− CLL/SLL have been reported. In addition, CD5 is not an exclusive marker for lymphoid cells; its expression has been observed in several non-hematopoietic neoplasms. This report briefly reviewed and discussed CD5− CLL/SLL and CD5+ carcinoma reported in the literature.

The diagnostic value of nipple discharge cytology: Breast imaging complements predictive value of nipple discharge cytology

Papilloma is the most common finding associated with pathologic nipple discharge. In the absence of breast imaging abnormalities, the incidence of occult malignancy is <3%. To determine the predictive value of nipple discharge cytology in conjunction with breast imaging. Retrospective review of 160 charts; inclusion criteria of clinically pathologic nipple discharge, subsequent excisional biopsy, and absence of palpable abnormalities. Nipple discharge cytology categorized as negative, atypical, suspicious, and papillary. Breast imaging was analyzed. Preoperative tests were correlated to final surgical pathology. 89 patients identified. Sixty-five had positive cytology, with a false positive rate of 32.3%. They were associated with papillomas in 52%, benign non-papillary in 33% and malignant lesions in 9% of cases. Nipple discharge cytology was positive in 69.6% of papillomas and 92% of atypical/malignant lesions; 30% had abnormal breast imaging and positive cytology. Nipple discharge cytology had a sensitivity of 74.5%, specificity of 30%, and positive predictive value of 68%. The positive predictive value increased to 85% with associated abnormal breast imaging. Nipple discharge cytology is useful in evaluating pathologic discharge. However, negative cytology with negative imaging is not enough to avoid surgery in cases of suspicious clinical presentation.

Rhabdomyosarcoma of the Skin Resembling Carcinosarcoma: Report of a Case and Literature Review

Rhabdomyosarcomas (RMSs) are soft tissue sarcomas with skeletal muscle differentiation. Cutaneous RMSs are exceedingly rare, and in most cases, they represent metastatic disease or the dermal involvement by a tumor arising in the underlying soft tissues. We herein report the case of a 41-year-old man who developed a cutaneous swelling of the right nasal orbital angle. An initial incisional biopsy showed cytokeratin-positive atypical spindle cells forming long and intersecting fascicles, thus the case was diagnosed as carcinosarcoma. In the subsequent excisional biopsy, the skeletal myogenic differentiation of the tumor cells infiltrating the dermis and subcutis was demonstrated by morphology (presence of rhabdomyoblasts), immunohistochemistry (positivity for desmin, myogenin, myoglobin, and actins), and electron microscopy (evidence of rudimentary sarcomeric structures). A final diagnosis of primary cutaneous RMS was made. The patient was subjected to postoperative radiation and chemotherapy, but after 4 months, the patient developed a tumor recurrence followed by distant metastases and death. Review of the literature reveals that RMSs of the skin are often underrecognized and display peculiar clinical features in comparison with their more common soft tissue counterpart.

P5-09-04: Predictors of Malignancy and Surgical Outcomes Following Indeterminate Core Needle Biopsy in the British Breast Screening Programme.

Abstract Background: The National Health Service Breast Screening Programme (NHSBSP) invites women between 50 and 70 years for mammography every three years, with abnormal imaging leading to further assessment. Core needle biopsy (CNB) is the standard for obtaining a definitive pre-operative diagnosis. However a proportion of CNBs will be reported as showing indeterminate pathology, with uncertain malignant potential. This necessitates surgical diagnostic excision biopsy, with attendant potential morbidity, and highlights the importance of pre-operative diagnosis. This study aimed to categorise the histological lesions prompting B3 classification arising within a screening programme, and to quantify the definitive surgical outcomes following excision biopsy. Material and Methods: Data was collected retrospectively from January 2000 — December 2010, including demographic details, radiological presentation, relevant clinical findings, results of preoperative investigations, reports of diagnostic excision biopsy and subsequent surgical management. Patients were included if they had a B3 CNB result and subsequent excision biopsy, following attendance for screening mammography. Primary outcome was classification of B3 lesions and positive predictive values (PPV) for malignancy. Secondary outcomes were subsequent surgical procedures. Results: There were 239 B3 lesions, representing 7.1% of all CNB carried out within the screening programme. Mean patient age was 55.6 years, and median lesion size was 14.5 mm (range: 4–25mm). Eighty seven lesions (36.4%) were malignant on excision: 28 (11.7%) invasive and 52 (21.8%) in situ. Lesion specific PPVs for malignancy were as follows: phyllodes tumour 50.0%, atypical ductal hyperplasia 40.0%, columnar cell lesion 40.0%, papillary lesion 26.7%, lobular neoplasia in situ 26.7%, and radial scar/complex sclerosing lesions (RS/CSL) 25.9%. The PPV of RS/CSL with atypia was 65.2%, and without 25.8%. Of 87 malignant cases, 55 (63.2%) went on to have a further surgery. 27 (50.9%) had re-excision of surgical margins, 10 (18.2%) had a mastectomy, 8 (14.5%) had a wide local excision, 2 had an axillary biopsy and one patient had a quadrantectomy. 18 patients had two further operations, the second was most commonly an axillary clearance, and 3 patients had three further operations. Discussion: B3 lesions are heterogeneous in nature, and continue to mandate surgical excision, demonstrated by a PPV of 36.4%, the highest reported figure in the literature to date. B3 CNB represents a significant surgical workload, demonstrated by the fact that 63.2% cases go on to have further surgery, and that 8.8% will require more than one further operation. Currently there is no pre-operative investigation that reliably predicts the likelihood of B3 associated malignancy. It has been demonstrated that the use of large volume vacuum assisted biopsy can reduce the rate of under diagnosis of both in situ and invasive malignancy, and this would clearly reduce the requirement for repeated surgery reported in this study. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-09-04.

Diagnostic Usefulness of Flow Cytometry for Immunophenotyping Classical Hodgkin LymphomaThe Authors’ Reply

To the Editor We read with interest the comprehensive evaluation of the value flow cytometric evaluation of fine-needle aspirate (FNA) specimens by Savage and coworkers.1 In this study, the authors demonstrated the clinical usefulness of flow cytometry (FC) for the workup of FNAs, specifically demonstrating overall FC sensitivity and specificity of 85.8% and 92.9%, respectively, when compared with a “gold standard” of histologic examination of a subsequent excisional biopsy specimen, FNA diagnosis, or clinical course. However, we respectfully disagree with one of the authors’ assertions in the discussion section that “…it is nearly universally …

Outcome of cervical intraepithelial neoplasia 2 diagnosed by punch biopsy in 131 women

To study the outcome of biopsy-diagnosed cervical intraepithelial neoplasia (CIN) 2 in patients treated by loop electrosurgical excision procedure (LEEP) or cold knife cone biopsy (CKC). Patients (n = 131) were analyzed for histological results on LEEP/CKC specimen. Demographic and risk factors, referral cytology, high risk human papilloma virus (HR HPV) test and follow-up colposcopic clinic visits were studied. Excisional specimens from LEEP/CKC demonstrated no CIN in 20 (15%), CIN 1 in 17 (13%), CIN 2 in 57 (44%) and CIN 3 in 37 (28%). No invasive cancers were identified. The referral Pap smear was high grade or possible high grade in 52 (40%), low grade in 59 (45%) and inconclusive in 20 (15%). Fourteen patients (11%) had positive excisional margins, eight of the 14 were tested for HR HPV infection before LEEP, and all were positive. Post-treatment HPV testing was performed at the 12-month visit in 6 of the 14 patients who had positive excision margins, and all 6 tested were negative. Two women (1.5%) with clear margins had recurrence of CIN 2, both tested positive for HR HPV after treatment. Our data showed that a significant number of women (28%) with biopsy-diagnosed CIN 2 had CIN 1 or no dysplasia on subsequent excisional biopsy. The recurrence risk of high grade dysplasia in CIN 2 is low (1.5%). However, due to the high number of patients (72%) with high grade dysplasia at treatment biopsy, caution needs to be exercised when a conservative approach is adopted in the management of CIN 2.

Childhood intramuscular lipoma with a novel three way translocation. a case report

Lipomas are common benign adipocyte tumours of adults, and frequently exhibit clonality, with karyotypic anomalies occurring in approximately two-thirds of adult cases. In contrast, lipomas are exceptionally rare in childhood. We describe an intramuscular lipoma in the back of a healthy 5-year-old boy, with the initial MRI examination showing features suspicious of rhabdomyosarcoma. An incisional biopsy and a subsequent excisional biopsy were performed and both confirmed the lesion to be a lipoma. Cytoge-netic analysis demonstrated a three way translocation involving chromosomes 8q12, 17q25 and 13q14. The 8q11–13 breakpoints are common in lipoblastomas, but are rare in lipomas. It has been postulated that rearrangements involving this chromosomal breakpoint is associated with up-regulation of the PLAG1 gene. The 13q14 breakpoint is associated with a subset of lipomas, usually involving deletion of material from 13q with a minimal region of deletion identified in band 13q14. Our patient’s karyotype does not show a visible deletion, therefore a molecular technique would be required to investigate the possibility of submicroscopic deletion or rearrangement at this site. Lipomas in childhood are known to occur as part of the Bannayan-Riley-Ruvalcaba syndrome and Aicardi syndrome. Our patient is a normal, healthy 5-year-old child.

Abstract P6-01-02: Flat Epithelial Atypia of the Breast on Core Needle Biopsies — To Re-Excise or Not

Abstract Flat epithelial atypia (FEA) of the breast have a tendency to calcify, and as such, are becoming increasingly detected by mammography. There is no consensus yet on whether to excise these lesions or not after diagnosis on core needle biopsies (CNB). We reviewed 3948 consecutive mammotome breast CNB from our surgical pathology files between June 2004 and June 2009 correlating histomorphologic, radiological, and clinical features. Diagnosis of FEA was made based on the 2003 WHO definition (replacement of native epithelial cells by a single layer of mildly atypical cells often with apical snouts, or proliferation of a monotonous atypical cell population in the form of stratification of uniform, cuboidal to columnar cells generally up to 3-5 cell layers with occasional mounding). There were145 (3.7%) cases of pure FEA and 58 (1.5%) cases of concomitant FEA and atypical ductal hyperplasia (ADH). In the pure FEA population, the age range was 33-82 years (median 49 years) and 67 patients (67.4%) had calcifications on mammography. There were 95 patients of the pure FEA group who underwent subsequent excisional biopsies with the following findings: Benign-19(20%), ADH-36(38%), Ductal carcinoma in situ (DCIS)-1(1.05%), DCIS and invasive ductal carcinoma (IDC)-2 (2.10%), atypical lobular hyperplasia (ALH)-3 (3.15%). In the concomitant FEA and ADH group, the age range was 34-83 years (median 51.50), and 50 patients (86.2%) had calcifications on radiograph. Of these, 44 patients underwent subsequent excisions with the following findings: Benign-10(22.7%), DCIS-4 (9.09%), DCIS and IDC-2(4.54%), DCIS+lobular carcinoma in situ (LCIS) + Invasive lobular carcinoma (ILC)-1(2.27%), papillary carcinoma-1(2.27%), and tubular carcinoma-1(2.27%). The incidence of carcinoma in the FEA+ADH group is about 20% (9 out 44) and 3% (3 out of 95) for the pure FEA group. This difference is statistically significant (p=0.0016). The relative risk of carcinoma findings in the ADH+FEA group versus the pure FEA group is 6.4773, 95% CI: [1.8432, 22.76 24]. These findings suggest that pure FEA in spite of having an association with carcinoma, albeit a low association, has a greater association with ADH, a well known risk factor for development of breast cancer. The contentious issue, however, still remains what to do with FEA when diagnosed by CNB since there is no consensus on the clinical management. Additional studies are needed to further understand the natural history of these lesions and provide a guide for their management. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-02.

The Use of Multispectral Imaging Combined with Quantum Dots In Fine Needle Aspiration Biopsies of Reactive Lymphoid Hyperplasia and Follicular Lymphoma

AbstractAbstract 3109 Background:Despite controversies regarding the ability of fine needle aspiration in diagnostic workup of lymphomas, authorities report widespread use of this diagnostic procedure. In this regard, cytologic distinction between reactive lymphoid hyperplasia (RLH) and small cell lymphomas, such as follicular lymphoma (FL), are especially difficult in fine needle aspirations (FNA). The use of ancillary tests in these cases is crucial, and often includes flow cytometry (FC), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH). The interpretation of IHC can be challenging due to the subjective and qualitative nature, in addition to the need for multiple sections for analysis of multiple antibodies. The FC and FISH require ample appropriate material which is sometimes not available due to the scanty yield of FNA procedure. Multispectral imaging (MSI) with quantum dots (QDs) uses highly fluorescent molecules that allow multiple spectra to be distinguished when used in combination, which allows for more precise signal quantitation. Briefly, QDs are semiconductor nanocrystals that possess unique properties of an extremely high fluorescence efficiency and lack of photobleaching due to their inorganic composition, making them ideal fluorophores. They can absorb light over a wide range of wavelengths, and due to their precise crystalline structure, their emission spectrum is tightly defined. Furthermore, their emission wavelength is tunable during synthesis producing a range of narrow emission spectra with little overlapping. The remarkable spectral properties of QDs allow easy multiplexing, and therefore more information can be acquired from fewer samples, an ideal property while working with FNA samples. An additional advantage of fluorescence detection is a more precise signal quantitation compared to chromogenic methods. Consequently, QDs have potential for multiplex biomarker quantitation. Thus, we examined the ability of MSI to provide quantitative and useful data to help in distinguishing RLH and FL in FNA biopsies, which might improve the diagnostic accuracy rates of FNA. Design:A total of 8 FNA cell block sections from 4 RLH and 4 FL cases were stained using immunohistochemical stains (CD3, CD20, CD10, and bcl-2) conjugated to quantum dot fluorophores. A series of slides were also used for controls and for creating a spectral library on the Nuance CRI Flex microscopy system (CRi, Cambridge Research & Instrumentation, Woburn, MA; spectral range 420 to 720 nm). A total of 3 fields of view (FOV) at 10x magnification were captured for each case and analyzed using the Nuance software version 2.10. Results:All 8 cases were from FNAs of lymph nodes and had confirmed diagnosis in subsequent excisional biopsy or complete immunophenotyping/molecular data. The analysis of the 24 FOV revealed that the FL cases tended to show significantly more CD20-positive cells than CD3-positive cells (lower CD3:CD20 ratio; 0.3 vs. 3.9), and tended to have more pixels colocalizing CD20/CD10/bcl-2. For quality control purposes, the average percent of pixels colocalizing CD3 and CD20 was less than 0.4%. Conclusions:This study shows that MSI is feasible on FNA cell block material and can be helpful in obtaining quantitative data from multiple antibodies used on a single slide. This allows a potentially objective reproducible quantitative expression of different antigens to be determined on a single slide which may be advantageous in FNA samples with limited material and may potentially be helpful in the cytologic distinction of RLH and FL. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Displaced Epithelium After Liposuction for Gynecomastia

The authors describe the case of a 36-year-old man with gynecomastia who was previously treated with liposuction of the breast for cosmetic purposes. Histologic examination of a subsequent excisional biopsy revealed nests of displaced epithelial cells in adipose tissue. Epithelial cell displacement is a well-known risk of core needle biopsies and fine-needle aspirations of breast lesions. However, to the authors' knowledge, epithelial displacement in gynecomastia after liposuction, mimicking invasive ductal carcinoma, has not previously been reported.

Accurately Assessing HER-2/neu Status in Needle Core Biopsies of Breast Cancer Patients in the Era of Neoadjuvant Therapy: Emerging Questions and Considerations Addressed

Emerging data show that patients with operable, HER-2/neu overexpressed/amplified breast carcinomas have significantly better responses (more frequently obtaining pathologic complete response and greater percent disease-free survival) when treated with trastuzumab (Herceptin) simultaneously with neoadjuvant chemotherapy than with chemotherapy alone. With the increasing use of neoadjuvant therapies, clinicians require information on biomarkers including HER-2/neu status at the time of needle core biopsy. Concordance rates between fluorescence in situ hybridization (FISH)-determined HER-2/neu status on needle core biopsies and on subsequent excisional biopsies of the same tumor have not been well studied. Moreover, the practice of automatically performing ("reflexing") 2+ immunohistochemical (IHC) staining needle core biopsies for FISH analysis on the same sample needs to be validated. In this study, we set out to (1) determine the accuracy of HER-2/neu status as determined by FISH on needle core biopsy material compared with FISH on the subsequent excisional biopsy of the same tumor with special consideration of IHC 2+staining cases and (2) determine the constancy of HER-2/neu status in pre-neoadjuvant and post-neoadjuvant chemotherapy-treated tumor in the form of needle core biopsy and excisional biopsy samples, respectively. 100 patients whose needle core biopsies and subsequent excisional biopsy samples were pathologically evaluated at our institution were studied. For each patient, unstained sections from both specimens were prepared and used for IHC or FISH. IHC was carried out using the HercepTest kit (DAKO, Carpinteria, CA). Parallel unstained slides were used to carry out FISH (dual probe, Vysis). Statistical analyses were carried out on the resulting data generated after interpretation. The concordance rate between FISH results determined on the needle core biopsy and subsequent excisional biopsy of the same tumor was 86% (kappa=0.56, P=2x10). If equivocal FISH cases (> or =1.8 to < or =2.2 amplification ratio) in a needle core biopsy or excisional biopsy specimen or both, were excluded, the concordance rate increased to 95% (kappa coefficient=0.86, P=2x10). Fourteen of 100 (14%) cases showed 2+ IHC staining in the needle core biopsy specimen with good concordance of FISH-determined HER-2/neu status between the needle core biopsy and excisional biopsy specimens (79% agreement and kappa=0.512, P=0.05). Nine, 3, and 2 cases of the 14 cases were amplified, equivocal, and negative on the excisional biopsy specimens, respectively. Of the 15 patients who received neoadjuvant chemotherapy, 93% and 87% had no change in HER-2/neu status as determined by IHC or FISH, respectively, in the excisional biopsy specimen when compared with that determined on the prior core biopsy sample. Excellent overall concordance was achieved between FISH-determined HER-2/neu status on the needle core biopsy and that determined on the subsequent excisional biopsy of the same tumor. These results suggest that intratumoral heterogeneity of HER-2/neu assessed by FISH is not a significant confounding factor when analyzing smaller sized samples. Furthermore, 79% of 2+IHC staining needle core biopsy cases showed concordant FISH results in the needle core biopsy and subsequent excisional biopsy specimens. Our results show good concordance, however, larger cohorts need to be studied to verify this finding. HER-2/neu status remains unchanged in the majority of cases when comparing pre-neoadjuvant and post-neoadjuvant chemotherapy-treated specimens.

Lobular neoplasia displaying central necrosis: A potential diagnostic pitfall

The distinction between intraepithelial proliferations of ductal and lobular type is often straightforward. However, a small number of cases create diagnostic problems even for experienced pathologists. Among those is the recognized, but not always kept in mind, lobular neoplasia with “comedo-type” necrosis. Herein, we present six cases of lobular neoplasia with comedo necrosis. Three cases were classified correctly, whereas the three remaining cases were initially misdiagnosed as ductal carcinoma in situ with necrosis. Of these three misdiagnosed cases, one patient underwent radiation therapy before this study was carried out. The two other patients were correctly reclassified as lobular type in subsequent excisional biopsies. One case showed a focus of microinvasion. All six lesions were negative by E-cadherin immunohistochemistry. Our experience highlights that the correct differentiation between intraepithelial neoplasias of ductal and lobular type may be challenging, and that the correct differentiation is extremely important for prognostic information and therapeutic decisions.