Node Core Biopsy Research Articles

A-237 Positron emission tomography/computed tomography guided choice of lymph node core biopsy. A useful tool

A-237 Positron emission tomography/computed tomography guided choice of lymph node core biopsy. A useful tool

Improving resource utilization: Axillary lymph node core biopsy triaging for lymphoma.

To evaluate the utilization of hematopathology resources within our enterprise on axillary lymph node core biopsy (AxLNCB) specimens, particularly those obtained in the context of breast cancer screening. The utilization of hematopathology resources was determined for all AxLNCB specimens over a 30-month period from across our enterprise, and chart review was performed for select patient demographics and radiographic features. The AxLNCB cases with benign histology were reviewed for subtyping of histologic patterns. Of the total 594 AxLNCB specimens, 61.6% were benign and 38.6% malignant. Of malignant cases, only 9.3% contained any hematologic malignancy, yet 94% of all cases received tissue triage for lymphoma, and 81% were reviewed at least in part by a hematopathologist. Six clinical parameters were found to independently predict risk of hematologic malignancy: male sex (P = .041), bilateral lymphadenopathy (P = .004), diffuse cortical thickening (P = .005), lack of breast cancer (P = .001), older age (P < .001), and history of hematologic malignancy (P < .001). Our enterprise overused hematopathology resources in the evaluation of AxLNCB performed in the study period. Our process could improve from the application of a simple tool generated from this cohort to predict percent risk of the specimen containing hematologic malignancy using patient characteristics easily found via routine chart review.

Lymphoma Diagnosis and Classification Using Next Generation Sequencing of 30 CD Markers and Machine Learning As an Alternative to Immunohistochemistry

Introduction: Lymphoma diagnosis and classification requires pathologist interpretation of morphology and large numbers of immunohistochemistry (IHC) stains of various CD markers. This process is subjective and requires a significant amount of tissue. In contrast, RNA quantification of the same CD markers used in IHC using next generation sequencing (NGS) requires little tissue and is less influenced by the antigen retrieval process used in IHC. However, IHC staining and microscopic examination allows evaluation of the expression in various subpopulations and makes diagnosis possible. In contrast, when total RNA is evaluated by NGS, distinguishing between subpopulations is lost. Machine learning algorithms are capable of multi-marker normalizing and compensate for the loss of subpopulation analysis. To confirm this, we explored the capability of using RNA quantification of 30 CD markers by NGS from FFPE tissue along with machine learning in the clinical diagnosis and classification of various types of lymphoma. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue from 130 diffuse large B-cell lymphoma (DLBCL), 70 mantle cell lymphoma, 92 T-cell lymphoma, 48 follicular lymphoma, 36 Hodgkin lymphoma, and 52 marginal zone lymphoma samples were used for extracting mRNA. The studied samples were consecutive without selection and included mainly lymph node excisional biopsies or core biopsies. RNA sequencing was performed using a targeted hybrid capture panel that included CD1A, CD2, CD3D, CD3E, CD3G, CD4, CD5, CD7, CD8A, CD8B, CD10, CD14, CD19, CD20, CD22, CD33, CD34, CD38, CD40, CD44, CD47, CD68, CD70, CD74, CD79A, CD79B, CD81, CD138, CD200, and CD274 genes. Salmon v1.4.0 software was used for expression quantification (TPM). Random forest machine learning algorithm was used for predicting diagnosis. Randomly selected two thirds of samples were used for training and one third was used for testing. Results: In some cases, diagnosis can be made by simply inspecting the RNA levels of various CD markers. However, machine learning shows remarkably high sensitivity and specificity in the diagnosis of most lymphoma subclasses. Area under the curve (AUC) was at 1.00 (95% CI: 1.000-1.00) for DLBCL vs. T-cell lymphoma, Hodgkin vs. T-cell, Hodgkin vs. DLBCL, mantle vs. DLBCL, and Follicular lymphoma vs. marginal lymphoma with 100% sensitivity and specificity in the testing set. AUC was at 0.974 (95% CI: 0.920-1.000) for marginal lymphoma vs. mantle cell lymphoma with sensitivity of 88% and specificity of 100%. The AUC was at 0.887 (95% CI: 0.776-0.999) for follicular lymphoma vs. DLBCL with sensitivity of 81.3% and specificity of 83.7%. Conclusions: This data demonstrates that NGS quantification of RNA from 30 CD markers when combined with machine learning is adequate for reliable classification of various types of lymphoma. This approach can provide valuable information to distinguish between difficult diagnoses, and if trained adequately has the potential to expand to more borderline cases. More importantly, this technology can be automated and less susceptible to human errors. RNA quantification using NGS has the potential to replace the need for IHC and can be applied when samples are limited such as in needle aspiration or core biopsies.

An Unusual Presentation of Glandular Fever

Epstein-Barr virus (EBV) is an ubiquitous DNA herpesvirus with >90% of adults >40 years of age showing a serological response. While in their youth, primary EBV infection may pass unnoticed, young adults have a high incidence of infectious mononucleosis (IM). This is characterized by a triad of pharyngitis, cervical lymphadenopathy, and fever because of a self-limiting lymphoproliferative disease. Common complications include but are not limited to hepatitis, splenomegaly, encephalitis, and haemophagocytic lymphohistiocytosis (HLH) with evidence that Caucasian males and smokers are more likely to suffer severe disease. Here we present a 21-year-old male who presented with a 2-week history of fever, dry cough, and a 4-week history of pharyngitis. He had no exposure to unwell contacts and denied any new sexual partners. Examination revealed general pallor with tender bilateral cervical lymphadenopathy and pharyngeal erythema. Admission bloods revealed pancytopenia (WCC 1.5 × 109/L, Plt 84 × 109/L, and Hb 82 g/L) with normal reticulocyte count and raised mean corpuscular volume (114 fL). Serum vitamin B12 and folate were low with serum ferritin raised (1027 µg/L) suggesting a proinflammatory state. Admission liver function tests, coeliac serology, autoimmune panel (ANA, ANCA, and anti-dsDNA), hepatitic (hepatitis A, B, and E), human immunodeficiency virus (HIV), toxoplasmosis, parvovirus, and CMV serology were normal. The monospot test on day 1 of the presentation was negative. Ultrasound (US) of the abdomen on day 3 of the presentation revealed isolated splenomegaly (16.8 cm). Day 4 EBV serology (VCA IgM, VCA IgG, and EBNA IgG) was negative as such haematological investigations including JAK2, serum free light chains, and BCR-ABL were undertaken alongside cervical lymph node core biopsy. Repeat Monospot testing on day 7 came back positive. Repeat EBV serology now showed equivocal EBV VCA IgG (0.77 OD) and positive VCA IgM (9.04 OD) with concurrent new hepatitis. Histopathology of the core biopsy revealed Sternberg-reed cells and a mixed immunoblastic reaction in keeping with resolving IM. This case highlights the need for physicians to have a strong clinical suspicion of IM and understand the multiple ways in which IM may be present as well as the time lag to positivity in serological testing.

Abstract P4-06-06: Role of lymphatic SEC62 expression in prediction of treatment response in patients undergoing neoadjuvant chemotherapy for primary breast cancer

Abstract Background Chromosome 3q26 amplifications have been shown to represent a frequent alteration in various cancer entities including breast cancer. SEC62 - a 3q26 encoded gene - was identified as a potential onco- and tumor-driver gene for the pathogenesis of breast cancer. Sec62 seems to induce an increased stress tolerance, enhanced cell migration and proliferation in SEC62 overexpressing cells. Patients with SEC62 overexpressing breast cancer have been shown to have a higher rate of lymph node metastasis and poorer overall prognosis. Hence, we aspired to further evaluate the function of lymphatic SEC62 expression and its predictive role on the response to neoadjuvant chemotherapy. Objectives We aimed to assess the role of lymph node SEC62 expression as a predictive biomarker for response to neoadjuvant chemotherapy, besides we sought to evaluate potential differences in SEC62 expression levels in metastatic lymph node core biopsies and final pathology specimen according to breast cancer subtype. Material &amp; Methods All nodal positive patients treated for primary breast cancer with neoadjuvant chemotherapy at the Department of Gynaecology and Obstetricts, Saarland University Hospital, Homburg, Germany between 01/2009 and 12/2019 were enrolled in this retrospective study. We analyzed SEC62 expression in tissue samples by immunohistochemistry (IHC). Sec62 immunoreactivity was evaluated using the immunoreactive score (IRS) according to Remmele and Stegner (0-12). For the assessment of the Sec62 protein content of the tumor cells, we rated Sec62 “low” for a score of 0-8, and “high” for 9-12 as described in previous publications. IHC was performed on initial lymph node core biopsy (CB) tissue (pre-treatment) or sentinel node biopsy specimen and on definite pathology specimen (PS) obtained during axillary dissection after completion of neoadjuvant chemotherapy.SEC62 expressions in both samples were compared and correlated with response to neoadjuvant chemotherapy, evaluated pathologically using the semi-quantitative response to neoadjuvant chemotherapy scoring system by Sinn et al. ranging from 0 (no effect) to 4 (no tumor detectable). Results 103 patients were assessed for eligibility. 15 cases were excluded, due to incomplete clinical information or insufficient slide quality, leaving 88 patients for final analysis. Median patient age was 55 (32-78) years and median response to neoadjuvant chemotherapy score of 2 (0-4). 11 (12.5%) patients had luminal A, 31 (35.2%) luminal B, 21 (23.9%) Her2/neu positive and 25 (28.4%) triple negative breast cancer. Median SEC62 expression in lymph node core biopsies was significantly higher compared to expression in final specimen (p&amp;lt;0.01). While no differences in basic expression of SEC62 in CB and the response to neoadjuvant chemotherapy were detected, patients with an IRS score ≤ 8 in PS and patients with a difference of IRS score ≥6 between CB and PS showed a significantly higher median response to neoadjuvant chemotherapy score compared to other patients (p&amp;lt; 0.01). Analyzing median Sec62 IHC expression in final pathology specimen, we observed significantly lower Sec62 scores for Her2/neu positive and triple negative patients compared to other subtypes (p&amp;lt;0.01). Median SEC62 expression showed the highest decrease between CB and PS in Her2/neu positive and triple negative patients. Regarding response to neoadjuvant chemotherapy, the effects described above could be observed in all breast cancer subtypes, but were strongest in triple negative patients. Conclusion We identified lymph node SEC62 expression as a promising biomarker for prediction of response to neoadjuvant chemotherapy in breast cancer patients. This effect seems to be strongest in patients with triple negative breast cancer. Citation Format: Julia Zimmermann, Anna Jung, Merle Doerk, Mariz Kasoha, Barbara Linxweiler, Maximilian Linxweiler, Mathias Wagner, Rainer Bohle, Marc Radosa, Erich Solomayer, Julia C Radosa. Role of lymphatic SEC62 expression in prediction of treatment response in patients undergoing neoadjuvant chemotherapy for primary breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-06-06.

Mixed Hepatocellular-Cholangiocarcinoma Tumors: A Disease on a Spectrum

Introduction: Mixed hepatocellular-cholangiocarcinoma (mHCC-ICC) is a rare type of primary liver cancer combining features of Hepatocellular Carcinoma (HCC) and Intrahepatic Cholangiocarcinoma (ICC). While surgical resection is the mainstay of treatment in resectable patients, the role of regional lymphadenectomy for mHCC-ICC is not well understood. Method: The NCDB database was queried for patients with HCC, ICC, mHCC-ICC. For our analysis, transplant and locoregional therapies were excluded from the surgical cohort. Lymph node aspiration or core biopsy was excluded from our lymphadenectomy cohort. Intergroup comparisons and Kaplan-Meier survival analysis was performed. Results: We identified a cohort of patients with HCC (n=14647), ICC (n=1682), and mHCC-ICC (n=401) that had undergone surgical resection for their disease. A regional lymphadenectomy was performed in 15.1% of HCC, 32.4% of mHCC-ICC, and 47.6% of ICC (p<0.001). Interestingly, there was a significant difference in the rate of lymph node metastasis depending on the histological subtype, with node positive pathology seen in 6.4% of HCC, 20.8% of mHCC-ICC, and 33.5% of ICC (p<0.001). Survival was significantly improved in patients who underwent surgical resection with a median overall survival (mOS) of 47.7 months for HCC, 32.0 months for mHCC-ICC, and 31.2 months for ICC (p<0.001). Conclusions: HCC, mHCC-ICC, and ICC appear to exist as subtypes on a disease spectrum with varying clinical outcomes. Although mHCC-ICC tumors share features of HCC, they have a higher rate of nodal metastasis and a decreased mOS more consistent with ICC. These data suggest that regional lymphadenectomy should be considered for mHCC-ICC.

P039 Muscle wasting &amp; weakness: a rare presentation of sarcoidosis

Background/Aims Sarcoidosis is a rare multisystem disease characterised by the presence of noncaseating granulomas. It most commonly affects the lungs though can affect any other organ system. Rarely, it can manifest as an acute myopathy. We describe a case of a patient presenting with muscle weakness and constitutional symptoms who was eventually diagnosed with sarcoidosis. Methods A 48-year-old male with a background of lumbar spondylosis and BPH, presented with a 6-week history of progressive upper and lower limb weakness, myalgia and reduced mobility. He also described an 18-month history of progressive fatigue, drenching night sweats and 10-kilogram weight loss. His symptoms meant he was unable to work as a firefighter. Examination demonstrated profound muscle wasting and reduced power in the proximal muscles of his upper and lower limbs. There was no evidence of rash, synovitis or lymphadenopathy. Blood tests showed a normocytic anaemia (Hb 100 g/L) and raised C-reactive peptide (180 mg/L) and erythrocyte sedimentation rate (100 mm/hour). The creatine kinase ranged between 20-42 units/litre. He had a weakly positive anti-nuclear antibody (1:80). The remaining autoantibody screen was negative including ENA, DSDNA, ANCA, rheumatoid factor and anti-CCP. Complement proteins were unremarkable. Furthermore, an extended myositis panel revealed no myositis-specific or myositis-associated antibodies. Serum calcium and angiotensin-converting enzyme (ACE) levels were normal. Blood cultures and virology screen including for HIV, hepatitis B, hepatitis C, CMV, EBV, COVID-19 and respiratory viruses were all negative. A chest radiograph was also unremarkable. Results He subsequently underwent electromyography which revealed generalised myopathy. An MRI of the lower limb proximal musculature showed evidence of muscle oedema worse on the right-side but no definitive evidence of myositis. A PET-CT followed revealing FDG-avid generalised lymphadenopathy and polyarticular uptake, but little uptake in the skeletal muscles. He underwent an external iliac lymph node core biopsy which demonstrated multiple noncaseating granulomas and lymphadenitis. Cultures for Tuberculosis were negative and there was no evidence of a lymphoproliferative disorder. A muscle biopsy was desired but not possible due to lack of availability because of the COVID-19 pandemic. The patient was diagnosed with sarcoidosis and commenced on three pulses of intravenous methylprednisolone followed by a weaning regimen of high-dose oral prednisolone and subcutaneous methotrexate. This resulted in a sustained improvement in his symptoms and normalisation of inflammatory markers. Conclusion Symptomatic myopathy is present in only 0.5-2.5% of sarcoidosis patients. This unique case highlights the heterogeneity of this disease and the vital role different diagnostic modalities play in achieving the correct diagnosis. It is also pertinent that the lymphadenopathy, found incidentally via imaging, led to the diagnosis. Although notoriously a diagnosis of exclusion, this case emphasises the importance of considering sarcoidosis even in the absence of respiratory symptoms, a raised ACE or hypercalcaemia. Disclosure C. Tomlinson: None. A. Khan: None. D. Mukerjee: None. N. Bhadauria: None.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a recently recognized type of T-cell lymphoma that can develop following breast implants, with morphologic and immunophenotypic features indistinguishable from those of ALK-negative ALCL. Here we report a case of a 58-year-old woman with a history of subglandular silicone implants placed for bilateral breast augmentation 25 years ago, who presented with bilateral breast pain and was found to have bilateral Baker Grade III capsular contracture, and heterogenous fluid collection centered near the left third costochondral articulation, a suspicious left chest wall lesion, and left axillary lymphadenopathy on imaging. A left axillary lymph node core biopsy and an aspiration of the fluid were performed, and no malignant cells were identified. The patient underwent bilateral removal of breast implants and total capsulectomies. Microscopic examination of the capsule surrounding the left breast implant revealed large pleomorphic tumor cells in a fibrinous exudate. By immunohistochemistry, the tumor cells were found to be positive for CD3 (subset), CD4, CD7, CD30 (strong and uniform), and CD43, and negative for CD2, CD5, CD8, and ALK1, supporting the diagnosis of breast implant-associated ALCL. No lymphoma cells were identified in the right breast capsule, confirmed by CD30 stain. Breast implant-associated ALCL is a very rare disease that can develop many years after breast implant placement. Proper evaluation with breast imaging and pathologic workup is essential to confirm the diagnosis in suspected cases. Our case highlights that adequate sampling is important in the investigation of patients with suspected breast implant-associated ALCL.

Diagnostic accuracy of core biopsy in patients presenting with axillary lymphadenopathy and suspected non-breast malignancy

IntroductionExcision biopsy has been the investigation of choice for patients presenting with pathological axillary lymphadenopathy without a breast abnormality. Core biopsy of nodes can provide sufficient tissue for diagnosis and has advantages in terms of morbidity and speed of diagnosis. This study evaluates the diagnostic accuracy of core biopsy in patients presenting with axillary lymphadenopathy. MethodsBetween 2009 and 2019, 165 patients referred to the Edinburgh Breast Unit had a total of 179 axillary lymph node core biopsies. Results152 (92%) of the 165 initial core biopsies were deemed to contain adequate nodal tissue. Core biopsy correctly established malignancy in 75 of the 78 patients with haematological malignancy (96%) and in all 28 patients with metastatic carcinoma (100%) and correctly diagnosed benign changes in 49 of 57 (86%) patients with benign conditions. There were no false positives and no false negatives. In 67 (85.9%) of the 78 patients with haematological malignancy there was sufficient material in the first core biopsy to allow the pathologist to make an actionable diagnosis and not ask for more tissue sampling prior to treatment. There were no complications of core biopsy. On follow up, none of the patients with benign cores has been shown to have malignancy in the axilla and none with lymphoma had their initial disease incorrectly classified. ConclusionsThis study shows that core biopsy is now the investigation of choice for patients presenting with axillary lymphadenopathy even in those suspected as having lymphoma.

Histiocytic necrotizing lymphadenitis with systemic lupus erythematosus mimicking like lymphoma

Histiocytic necrotizing lymphadenitis (HNL) is a rare idiopathic disorder. It is frequently underdiagnosed due to its nonspecific clinical features, mimicking like lymphomas, autoimmune diseases, and infectious reactive lymphadenopathy. Histological examination of the lymph node is the basis of diagnosis in HNL. We report a 40-year-old male patient who presented with fever for 4 weeks. After an extensive workup, laboratory investigations revealed progressive pancytopenia, gradual increase in serum lactate dehydrogenase, and ferritin with negative pyrexia profile. His radiological imaging including positron emission tomography/computed tomography showed multiple intra-abdominal, cervical, and axillary lymphadenopathies. Finally, the histological section from axillary lymph node core biopsy revealed a diagnosis of HNL. Subsequent autoimmune workup met diagnostic criteria for systemic lupus erythematosus. This case report alerts the clinicians regarding this rare disease and emphasizes the important role of morpho-histopathology in early recognition of this rare entity.

Lymph node core biopsies reliably permit diagnosis of lymphoproliferative diseases. Real-World Experience from 554 sequential core biopsies from a single centre.

Whilst excision biopsy is traditionally preferred, advances in radiological and histological techniques warrant a re-look at core biopsy as a viable primary diagnostic method. Over a 3-year period, all patients who underwent core biopsy to investigate lymphoma at our centre were included. 554 consecutive patients were included (40.1% prior lymphoma and 59.4% new presentations). Three or more cores were taken in 420 (75.8%) cases. Median time from request to biopsy and biopsy to histology report was 2 (0-40) days and 7 (1-24) days, respectively. 510/544 (93.8%) biopsies were diagnostic. There was no difference in whether the biopsy was diagnostic based on indication (new vs. relapsed lymphoma) (P=.445), whether biopsy was PET-directed (P=.507), for T-cell lymphoma (P=.468) or nodal vs. extra-nodal (P=.693). Thirty-eight patients (6.9%) required a second biopsy due to inadequate tissue. In a patient experience survey, only 13.9% reported any complications (1 self-limiting minor bleeding, 4 bruising) whilst 16.7% reported any discomfort beyond 12hours. Core biopsy performed by experienced radiologists and analysed by expert haemato-pathologists is a reliable, well-tolerated method for diagnosing lymphoma and confirming relapse. Multiple cores can be obtained under local anaesthetic yielding sufficient material in the majority of cases.

Does Contrast Enhanced Ultrasound (CEUS) of Normal/Benign Axillary Lymph Nodes in Patients with Breast Cancer Identify Significant Axillary Nodal Burden?

PurposeContrast enhanced ultrasound (CEUS) of the axilla allows preoperative identification and biopsy of the sentinel lymph node. Our aims were to evaluate the accuracy of the CEUS procedure for identifying axillary lymph node metastases preoperatively and compare the volume of axillary metastases in patients with malignant versus benign CEUS guided core biopsy at end of primary surgical treatment. MethodsRetrospective analysis of prospectively collected data on patients with breast cancer with normal axillary ultrasound or benign axillary FNAC undergoing preoperatively CEUS guided sentinel lymph node biopsy between 2013 and 2018. ResultsSLN was successfully identified by CEUS in 186 (90.7%) of patients with definitive diagnosis obtained in 163 (87.6%). Overall sensitivity was 55.77%, but significantly higher for high volume disease (77.78%) than for low volume disease (32.00%, odds ratio = 7.44, 95% CI = 2.16 to 25.62, p = .001) Specificity was 100%. NPV was 82.84% overall, 86.72% for low volume disease and 94.87 % for high volume disease. 72.4% of patients with initial malignant CEUS guided SLN core biopsy had two or more macrometastases at end of surgical treatment compared to 4.47% of patients with initial benign CEUS guided core biopsy. ConclusionWhen disease was present, CEUS guided sentinel lymph node core biopsy identify nodal metastases in 55.77% of patients with normal axillary grey scale ultrasound. This study suggests that the likelihood of extensive axillary disease at end of surgical treatment is low with an initial benign CEUS guided SLN core biopsy.

Abstract P1-02-03: Our preliminary experience: Ultrasound guided localization of axillary lymph nodes using activated charcoal before neoadjuvant chemotherapy for guidance in axillary surgery in breast cancer patients

Abstract The study objective is to review the rate of identification of the biopsied lymph node during surgery by placing activated charcoal in patients with node-positive breast cancer prior to neoadjuvant chemotherapy (NAC). The secondary objective is to validate the concordance of tattooed lymph node with the sentinel nodes resected during surgery at the final pathological examination. Background: The SENTINA study concluded that for cN1 breast cancer patients that had neoadjuvant chemotherapy and afterwards had two or more sentinel node localization examined, the false negative rate (FNR) was above 10%. The ACOSOG Z1071 study showed that clipping the positive lymph node and its preoperative localization reduces the false negative rate (FNR) significantly. The use of charcoal suspension for tattooing positive nodes during the biopsy is an effective and minimal invasive technique. It avoids placing a clip and posteriorly marking it with wire or radioactive seed previous to surgery, reducing the number of procedures, costs and time. When correctly placed charcoal suspension does not affect the pathological examination. Methods: This is a retrospective pilot study form January 2016 to March 2019 that enrolled 13 cancer patients aged (26 -50 years) with clinical T1-4, N 1-2, M0 in which NAC was performed. Ultrasound axillary lymph node core biopsy and tattooing with 0,3 ml of activated charcoal suspension (Mamograf ™) in positive lymph nodes was performed prior to NAC. Patients after NAC had axillary surgery. The sentinel nodes (SN) were identified as the nodes that contained blue dye and technetium-99m. During surgery both the SN, and also the tattooed lymph nodes were removed. Evaluation of the final pathological analysis concordance between the sentinel nodes and the tattooed lymph node was performed. Results: The analysis showed that surgeons were able to successfully identify the biopsied lymph node marked with activated charcoal in 11 (84,6%) cases. The final pathology results showed concordance between the sentinel nodes and the tattooed lymph in 11 cases. There were no cases in which the tattooed lymph node did not correspond to the sentinel node. In 2 (15,4%) cases charcoal wasn´t identified neither during the surgery nor during the pathological examination. No charcoal migration to other lymph nodes was identified during surgery and in all of the cases pathological examination was not affected when the final pathology was analyzed. The final pathology results in tattooed lymph nodes was of metastases in 4 cases (36,4%), post NAC nodal fibrosis in 2 cases (18,2%) and reactive adenitis in 5 cases (45,4%). Conclusion: When visualized on ultrasound, placing activated charcoal in patients with node-positive breast cancer prior to NAC, had shown to be successful and have a high identification rate during axillary surgery. This subset analysis provides preliminary information that using charcoal suspension for tattooing positive lymph nodes before NAC has a high identification rate during axillary surgery. Larger prospective studies may probe that this new technique may change clinical approach when it comes to identifying positive lymph nodes in breast cancer patients after NAC by successfully targeting and removing them with the need of fewer radiological exams and reducing surgical times as well as overall costs. Citation Format: Africa Pineiro, Maria L Cosaka, Mora Amat, Federico Colo, Maria L Negri, Juliana Marulanda Salinas, Varela Alejandra, Loza Martin, Ponce Carolina, Victoria Constanzo, Adrian Nervo, Daniel C Mysler. Our preliminary experience: Ultrasound guided localization of axillary lymph nodes using activated charcoal before neoadjuvant chemotherapy for guidance in axillary surgery in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-02-03.

Preoperative Ultrasound-guided Core Biopsy of Axillary Nodes for Staging of Clinically Negative Axilla in Breast Cancer Patients - A Pilot Study.

ObjectiveThe aim of the current study is to determine the feasibility and accuracy of ultrasound-guided core biopsy for staging the axilla in clinically node-negative patients with invasive breast cancer.IntroductionHistorically, in breast cancer patients, axillary lymph node dissection was performed to stage axilla. Because of the high morbidity of axillary lymph node dissection, sentinel lymph node biopsy (SLNB) became the standard of care in patients with clinically node-negative breast cancer. However, SLNB is expensive, time consuming, can cause morbidity and can be complicated by seroma formation, sensory nerve injury, lymphedema, etc. Many centers rely on the availability of frozen section on sentinel lymph nodes to avoid a second procedure with the accuracy of procedure ranging from 73 to 96%, however, the availability of frozen section is limited in our part of the world. Pre-operative identification of axillary node positivity in patients with clinically negative nodes by ultrasound imaging of the axilla would allow one-stage axillary clearance and can decrease the need for SLNB from 21% to 70%. The aim of the present study is to determine the accuracy and feasibility of ultrasound-guided core biopsy to stage the axilla in clinically node-negative breast cancer patients, comparing with final histopathology as gold standard.Material & methodsThis was a non-randomized, prospective interventional study, done at Radiology Department of Aga Khan University Hospital. All patients diagnosed with breast cancer (histologically proven) with clinically negative axilla and ipsilateral positive axillary ultrasound were included. These patients underwent axillary lymph node core biopsy. If the result was negative they were subjected to SLNB. Histopathology result was taken as gold standard.ResultsThe sensitivity of ultrasound-guided core biopsy was 88%, specificity 100%, positive predictive values (PPV) 100%, negative predictive values (NPV) 89.28%, diagnostic accuracy 94%.ConclusionIn conclusion, the present study demonstrated high accuracy of ultrasound-guided axillary lymph node core biopsy in breast cancer patients with clinically node-negative axilla. Positive core biopsy results can thus obviate the need for sentinel lymph node biopsy and allow breast surgeons to directly proceed to axillary lymph node dissection.

Atypical axillary lymphadenopathy mimicking an occult breast carcinoma in a patient diagnosed with sarcoidosis: case report

Introduction: Occult breast carcinoma is a rare presentation of breast cancer, with histological evidence of axillary lymph node involvement and clinical and radiological absence of malignant breast lesions. Its survival is similar to that of the usual presentation. The treatment consists of modified radical mastectomy or axillary drainage with breast irradiation, resulting in similar survival, associated with systemic therapy according to the staging. Neoadjuvant therapy should be considered in N2-3 axillary cases. Differential diagnoses of axillary lymphadenopathies include: non-granulomatous causes (reactive, lymphoma, metastatic carcinoma) and granulomatous causes (infectious – toxoplasmosis, tuberculosis, sarcoidosis, atypical mycobacteria). Objectives: To report the case of a patient who needed a differential diagnosis among the various causes of axillary lymphadenopathy. Methods: This is a literature review conducted in the PubMed database, using the keywords "granulomatous lymphadenitis", "breast sarcoidosis", "occult breast cancer". Inclusion and exclusion criteria were applied. Case report: V.F.S., female, 51 years old, was referred to an evaluation of axillary lymphadenopathy in May 2019. She was followed by the department of pulmonology due to mediastinal sarcoidosis since 2017. Physical examination indicated breasts without changes. Axillary lymph nodes had increased volume and were mobile and fibroelastic. Mammography revealed only axillary lymph nodes with bilaterally increased density, and the ultrasound showed the presence of atypical bilateral lymph nodes. Neither presented breast lesions. Axillary lymph node core biopsy was compatible with granulomatous lymphadenitis. This result corroborates the diagnosis of sarcoidosis affecting peripheral lymph nodes. The patient was referred back to the department of pulmonology, with no specific treatment since she is oligosymptomatic. Discussion: Despite the context of benign granulomatous disease, malignancy overlying the condition of sarcoidosis must be ruled out. The biopsy provided a safe and definitive diagnosis, excluding the possibility of occult breast carcinoma. The patient will continue to undergo breast cancer screening as indicated for her age and usual risk. Conclusion: In the presentation of axillary lymphadenopathy, the mastologist must know the various diagnoses to be considered. The most feared include lymphoma and carcinoma metastasis with occult primary site. A proper workup can determine the diagnosis and guide the appropriate treatment.

Neck as mediastinal extension: Diagnosis of sarcoidosis by core biopsy of cervical lymph nodes.

Sarcoidosis is a multi-system granulomatous disease. The diagnostic procedures for histological confirmation are invasive and a less invasive approach to diagnostic pathway is warranted. The utility of diagnostic value of neck ultrasound was retrospectively evaluated. A histological diagnosis was made by ultrasound-guided head and neck core biopsy to confirm clinically and radiologically suspected sarcoidosis. Twenty-five patients were referred for sonographic evaluation of the head and neck after CT scan in an attempt to avoid the use of more invasive tests. These patients had mediastinal adenopathy, but not clinically apparent neck nodes. Where no cervical lymph node suitable for biopsy was seen, parotid glands were biopsied if deemed abnormal. A diagnosis of sarcoidosis was made in all cases where a core biopsy of cervical lymph nodes was attempted. The cervical lymph nodesin this cohort were not particularly enlarged, short-axis dimensions being less than 10mm in majority, and they did not have any sonographic appearances to mark them as pathological. Nevertheless histological examination revealed non-caseating granulomas in all cases. In further two cases, where no neck nodes were seen, a histological diagnosis of sarcoidosis was made from biopsy of diffusely abnormal parotid glands. Given the clear advantages of cervical diagnosis in terms of invasiveness and economy compared to mediastinal alternatives, it is suggested that where the expertise for core biopsy of normal-sized cervical lymph nodes is readily available, the technique may be considered as a first-line investigation for the diagnosis of sarcoidosis.

A 62-Year-Old African American Woman With Stable Lymphadenopathy Over 5 Years

Abstract The patient is a 62-year-old African American female with medical history of Plummer Vinson syndrome and CT scan in 2014 showing lymphadenopathy of the porta hepatis. Needle core biopsy of enlarged lymph nodes revealed sheets of polytypic plasma cells with no aberrant B or T cells or granulomas or hyaline-like depositions identified. The findings were suspicious for unicentric Castleman disease. In 2019, the patient presented with chronic fatigue without other systemic symptoms. Contrast CT revealed persistent retroperitoneal lymphadenopathy and calcified granulomas in the liver, spleen, and lung. Excision of portal and celiac nodes showed preserved nodal architecture with mild mantle zone expansion and marked hyaline-like deposition in the follicles. Sheets of mature plasma cells and focally increased vasculatures were seen in the interfollicular areas. Focally frequent nonnecrotizing granulomas were noted. Occasional giant cells and rare asteroid bodies were identified in the granulomas. Immunohistochemistry stain workup revealed normal distribution of the B and T lymphocytes. CD138 stain highlighted marked increased plasma cells and HHV8 was negative. Immunofluorescence microscopy for kappa and lambda did not show monoclonality; IgA was positive in &lt;10% of plasma cells; special stain for Congo red and serum amyloid associated protein (SSA) IHC stain were strongly positive in the follicles. The overall findings are consistent with reactive lymphadenopathy with interfollicular polytypic plasmacytosis, noncaseating granuloma formation, and reactive amyloidosis. The features of mantle zone hyperplasia and polytypic plasmacytosis are suggestive of HHV8-negative/idiopathic unicentric Castleman disease. This case possibly represents an example of concurrent amyloidosis, sarcoidosis, and idiopathic unicentric Castleman disease. Given that SSA was recently reported to have a pathogenic role in granulomatous inflammation of sarcoidosis through sustained inflammatory reaction, the possibility of increased SSA triggering sarcoidoisis in this patient can be considered. However, the exact pathogenesis of these concurrent findings needs further investigation and clarification.

A Clinical and Pathological Comparison of Different Immunomorphological Subvariants of Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma at Initial Diagnosis

Background. Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) is a rare Hodgkin's lymphoma subtype with a variable growth pattern and immune tissue architecture of tumor. Clustering of patients into subgroups based on immunohistochemical (IHC) tumor subvariants is essential for prognosis assessment and development of new differentiated treatment approaches. Aim. To study clinical course of NLPHL in patients with different IHC-subvariants of the disease and identify a poor prognosis subgroup. Materials &amp; Methods. From 2010 to 2017 the Department of Anatomic Pathology at the National Medical Hematology Research Center undertook morphological and IHC-analysis of lymph node and bone marrow core biopsies of 60 NLPHL patients: 47 men and 13 women (male/female ratio of 3.6:1) aged 17-68 years (median 37 years). IHC-analysis with expanded panel of antibodies was performed in all cases of determining IHC-subvariants in accordance with WHO-2017 classification. Results. The clinical and immunomorphological comparative study of NLPHL with variant immune tissue architecture allowed to divide the patient population into three subgroups with differently manifested areas similar to T-cell/ histiocyte-rich large B-cell lymphoma (THRLBCL) in lymph node sections or other site biopsies. These subgroups are characterized by different clinical course of the disease. The subgroup with ≥ 50 % THRLBCL-like areas was marked by the prevalence of clinical stage IV and significantly larger amount of extranodal lesions. Conclusion. In NLPHL the most unfavorable clinical course is typical of the patients whose biopsies contain ≥ 50 % THRLBCL-like areas. Semi-quantification of THRLBCL-like areas allowed to define a spectrum of NLPHL IHC-subvariants correlating with the clinical course of the disease. The true transformation into diffuse large B-cell lymphoma is a rare event, it occurred in 2 (3 %) out of 60 patients.

EBUS Fine Needle Aspiration and Core Biopsy of Mediastinal Lymph Nodes: FNA Shows a Better Diagnostic Rate than Core Needle Biopsy

EBUS Fine Needle Aspiration and Core Biopsy of Mediastinal Lymph Nodes: FNA Shows a Better Diagnostic Rate than Core Needle Biopsy

Mixed phenotype (T/B/myeloid) extramedullary blast crisis as an initial presentation of chronic myelogenous leukemia

BackgroundChronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Philadelphia (Ph) chromosome generated by the reciprocal translocation t(9,22)(q34;q11). The natural progression of the disease follows a biphasic or triphasic course. Most cases of CML are diagnosed in the chronic phase. Extramedullary blast crisis rarely occurs during the course of CML, and is extremely rare as the initial presentation of CML. Case presentationHere, we report the case of a 32-year-old female with enlarged neck lymph nodes and fatigue. She was diagnosed with B-lymphoblastic leukemia/lymphoma with possible mixed phenotype (B/myeloid) by right neck lymph node biopsy at an outside hospital. However, review of her peripheral blood smear and her bone marrow aspirate and biopsy showed features consistent with CML, which was confirmed by PCR and karyotyping. An ultrasound-guided right cervical lymph node core biopsy showed a diffuse infiltrate of blasts, near totally replacing the normal lymph node tissue, admixed with some hematopoietic cells including megakaryocytes, erythroid precursors and maturing myeloid cells. By flow cytometry and immunohistochemistry, the blasts expressed CD2, cytoplasmic CD3, CD5, CD7, CD56, TdT, CD10 (weak, subset), CD19 (subset), CD79a, PAX-5 (subset), CD34, CD38, CD117 (subset), HLA-DR (subset), CD11b, CD13 (subset), CD33 (subset), and weak cytoplasmic myeloperoxidase, without co-expression of surface CD3, CD4, CD8, CD20, CD22, CD14, CD15, CD16 and CD64, consistent with blasts with mixed phenotype (T/B/myeloid). A diagnosis of extramedullary blast crisis of CML was made. Chromosomal analysis performed on the lymph node biopsy tissue revealed multiple numerical and structural abnormalities including the Ph chromosome (46–49,XX,add(1)(p34),add(3)(p25),add(5)(q13),-6,t(9;22)(q34;q11.2),+10,-15,add(17)(p11.2),+19, +der(22)t(9;22),+mar[cp8]). After completion of one cycle of combined chemotherapy plus dasatinib treatment, she was transferred to City of Hope National Cancer Institute for bone marrow transplantation. Discussion and conclusionDiagnosis of extramedullary blast crisis should be suspected in patients with leukocytosis and extramedullary blast proliferation. In this case study, we diagnosed extramedullary blast crisis accompanied by chronic phase of CML in the bone marrow. To our knowledge, this is the first reported case of extramedullary blast crisis as the initial presentation of CML with T/B/myeloid mixed phenotype. Other unusual features associated with this case are also discussed.