Excisional Node Biopsy Research Articles

Non-invasive detection of lymphoma with circulating tumor DNA features and plasma protein marker.

e19574 Background: Lymphoma is common cancer worldwide, a large group of lymphoid hematopoietic malignancies including Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) two major type. Lymphoma includes more than 30 unique subtypes, originating from B, T and NK cells. Currently, diagnosis and classification of lymphoma is based on excisional lymph node biopsy through immunohistochemistry and in situ hybridization. However, invasive biopsies have significant limitations and carry procedural risks to patients, and it cannot account for spatial inter- and intra-tumor heterogeneity due to sampling from only one location in a single tumor lesion. In the past few years, an emerging class of methods named Liquid biopsy can potentially improve on these limitations. Methods: 135 untreated stage I-IV lymphoma patients and 399 healthy individuals were enrolled in this study. 8ml peripheral blood was collected from each participant after enrollment. Cell-free DNA (cfDNA) was extracted and subjected to shallow whole-genome sequencing (sWGS), and partly plasma was used to quantify the expression of 7 tumor serum protein markers. We developed a newly blood-based assay, which integrated the newly next-generation technology of sWGS of cfDNA and protein marker (CA125), with artificial intelligence (AI) technology. Though our multi-dimensional assay, the cancer risk score (CRS) of each sample were calculated, and was used for lymphoma early diagnosis. Results: After compared each protein marker between lymphoma and healthy groups, only CA125 could be used to screen the lymphoma with a sensitivity of 25.9% at extremely high specificity 98.0% and an area under the curve (AUC) of 69.5%. As for the genomic feature of cfDNA, the characteristics of copy number aberrations (CNA) and fragment size (FS) were significantly different between lymphoma and healthy groups (p value < 0.0001 by student’s t-test). Both FS and CNA demonstrated improved sensitivity (36.3% and 67.4% respectively) compared to CA125. When the three signatures were incorporated into the CRS model, it achieved the best performance allowing 95 lymphoma cases to be identified with a sensitivity of 70.4% at 98.0% specificity, and an AUC of 88.0%. In stage I/II and III/IV lymphoma cases, the sensitivity was 40.0% and 85.7% respectively. For each lymphoma subtype, the lymphoma which from B-cell had higher sensitivity than that from NK/T cell (71.0% vs 64.3%), especially in HL (91.7%), all originated from B cell. Conclusions: We newly find the traditional protein marker CA125 can be used for lymphoma screening, which was integrated with genomic feature CNA and FS of cfDNA as a multidimensional assay for early detection of lymphoma with sufficient accuracy. The performance of our efficient and non-invasive assay for detecting lymphoma is 70.4% sensitivity at extremely high specificity 98.0%, especially for 40.0% sensitivity for early patients (stage I/II) screening.

Kikuchi-Fujimoto disease in a tertiary care teaching hospital in Coastal South India: A 8-year retrospective study.

A retrospective hospital-based descriptive cross-sectional study was conducted in tertiary care hospitals from 2011 to 2019. All patients with confirmed KFD diagnosis were included and after ethics committee approval the clinical details and histopathological data was retrieved from the medical records department and analyzed. A total of 67 cases were included. The mean age was 26.9±11.3 years with a female: male ratio of 1.9:1. There were 50 patients with tender cervical lymphadenopathy which was the most common clinical presentation. The mean length and width of palpable lymph nodes were 2.3±1.0 cm and 2.2±0.7 cm respectively. Histology revealed proliferative stage in majority of patients ( n=40, 59.7%). Lymphadenopathy resolved in 83.6% within 2 months. There were 42 patients who had complete recovery with symptomatic treatment within a period of 9 months. KFD is prevalent in young, female patients of Asian descent and often presents as tender cervical lymphadenopathy. Early diagnosis with excisional lymph node biopsy is crucial to avoid unnecessary investigations and treatment. Treatment is symptomatic unless complicated, where steroid therapy is considered. KFD has an excellent prognosis with almost no risk of fatality.

Urticarial rash with leukocytosis and monoclonal gammopathy

A 58-year-old man is being evaluated for a 4-year history of a diffuse, intermittent, nonpruritic rash associated with intermittent arthralgia, myalgia, generalized lymphadenopathy, night sweats, and unintentional weight loss of 10 pounds over 8 months. The symptoms did not appear in a predictable pattern each day or week. The rash was not responsive to oral antihistamines. Laboratory tests over the 4 years showed persistent leukocytosis (range 13,000-20,200/μL[13.5-20.2×109/L]) with neutrophilia (range 11.2-17.3×103/μL [11.2-17.3 109/L]), worsening anemia (hemoglobin concentrations of 13.2-11.0 g/dL [132-110 g/L]), elevated erythrocyte sedimentation rate (92 mm/h), C-reactive protein (154 mg/L), and ferritin (494 ng/mL [494 μg/L]), and monoclonal IgM-κ gammopathy. Workup for Lyme disease, hepatitis B and C, HIV, tuberculosis, and syphilis was negative. Antinuclear antibody, anti–double- and single-stranded DNA, rheumatoid factor, anti-SSA, and anti-SSB were negative, and complement levels were within normal limits. Bone marrow and excisional lymph node biopsies were unrevealing. Physical examination revealed erythematous wheals coalescing into plaques scattered symmetrically on the trunk and extremities (Fig 1). A punch biopsy of the left arm was performed (Fig 2).Fig 2By Devea R. De, BS; Alicia Goldenberg, MD; Paul N. Bogner, MD; Susan Pei, MD, FAAD.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Question #1: What is the most likely diagnosis?A.Adult-onset Still disease (AOSD)B.Schnitzler syndrome (SS)C.Systemic lupus erythematosus (SLE)D.Cryopyrin-associated periodic syndromeE.Urticarial vasculitis Click here to view disclosures, take the quiz, and claim CME credit. The authors have no conflicts of interest to declare. Consent for the publication of recognizable photographs was provided by the authors at the time of article submission to the journal stating that all patients gave consent for their photographs to be published in print and online and with the understanding that these photographs may be publicly available.

Sarcomatoid carcinoma of the prostate presenting as bilateral cervical lymphadenopathy: a rare case report

BackgroundSarcomatoid carcinoma (also called carcinosarcoma in the latest WHO classification 2016) of the prostate gland is a biphasic malignant neoplasm which exhibits epithelial and mesenchymal differentiation [1]. Sarcomatoid carcinoma is a rare tumour, considered as a variant of acinar adenocarcinoma in the WHO classification, with less than 200 reported cases in the literature to date [2]. Sarcomatoid carcinoma of prostate presenting with bilateral cervical lymph node deposits as the first clinical manifestation, is even rarer, and reported cases were not found in the literature; hence, this is the first case report of such, to the best of our knowledge.Case presentationWe report a case of sarcomatoid carcinoma of the prostate in a 72-year-old Sri Lankan man who presented with bilateral cervical lymphadenopathy. He had hard nodular prostate on digital rectal examination (DRE). Ultrasound scan of abdomen (USS) revealed the presence of paraaortic lymphadenopathy, in addition. The excision biopsy of the right cervical lymph node revealed deposit of a carcinoma of epithelioid histomorphology, which showed patchy strong positivity for immunohistochemical marker (IHCm), PSA. His serum PSA value was 48 ng/ml (reference < 5.40 ng/ml). Contrast-enhanced computed tomography (CECT) showed mildly enlarged prostate gland with irregular outline, sclerotic lesions in cervico-thoracic and lumbosacral vertebrae and generalized lymphadenopathy. Transrectal ultrasound guided biopsy of the prostate revealed sarcomatoid carcinoma. Disseminated sarcomatoid carcinoma of prostate was diagnosed. The patient has undergone bilateral orchidectomy, marking a serum PSA value of 5.4 ng/ml two months thereafter. He is surviving for six months after diagnosis and is currently under chemotherapy with docetaxel for the disseminated disease.ConclusionSarcomatoid carcinoma can present with cervical lymphadenopathy with absent lower urinary tract symptoms. In elderly patients with cervical lymphadenopathy, serum PSA, DRE and trans-rectal ultrasound scan are advocated to rule out prostate cancer. Immunohistochemical markers are required for the diagnosis of primary tumour and secondary deposit of sarcomatoid carcinoma of prostate.

Ultrasound Guided Biopsy in Patients With HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

To identify the differences in sensitivity and accuracy between ultrasound-guided and palpation-guided fine needle aspirations (FNA) of suspicious lymph nodes in patients with human papillomavirus (HPV) (+) oropharyngeal squamous cell carcinoma (OPSCC). Additional objectives included identifying patient specific factors affecting biopsy accuracy and evaluating potential differences in accuracy between fine and core needle biopsies. Retrospective chart review. A retrospective study of diagnostic sensitivity was completed at a single tertiary care center between 1/1/2006-12/31/2016. Participants included patients who underwent pretreatment FNA biopsy with HPV(+)OPSCC confirmed pathologically following neck dissection or excisional lymph node biopsy. A true positive (TP) on FNA biopsy was defined as an FNA biopsy concerning for squamous cell carcinoma (SCC) that was confirmed on excisional biopsy or neck dissection. A false negative (FN) was defined as a negative FNA but metastatic disease identified on excisional biopsy or neck dissection. Sensitivity was calculated as TPs/(TPs + FNs). Sensitivity was compared among techniques using chi-square and Fisher exact tests. A total of 209 FNA biopsies among 198 patients were included in the study, including 31 (15%) palpation-guided FNAs, 160 (77%) ultrasound-guided FNAs, and 18 (9%) ultrasound-guided FNA + core biopsies. Sensitivity was significantly different among palpation-guided FNA, ultrasound-guided FNA, and ultrasound-guided FNA + core biopsies (48% vs. 83% vs. 94%, respectively; P< .001) but there was no significant difference in sensitivity between ultrasound-guided FNA versus ultrasound-guided FNA + core biopsies (P= .31). The use of ultrasound guidance in FNA biopsies of nodal metastases in HPV(+)OPSCC improves sensitivity compared to palpation guidance alone. Ultrasound guided biopsies are preferred in patients with suspected nodal metastasis from HPV(+)OPSCC. 3 Laryngoscope, 132:2396-2402, 2022.

Myeloproliferative Syndrome With Eosinophilia Associated With Translocation t(8; 13) and T-cell Lymphoblastic Lymphoma: A Case Report and Review of the Literature

The 8p11 myeloproliferative syndrome (EMS) is an aggressive neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 tyrosine kinase gene on chromosome 8p11. We report the case of a 31-year-old man with no prior medical history who presents with two weeks of sore throat and cervical lymphadenopathy up to 5 cm. Initial peripheral blood examination showed leukocytosis with predominantly neutrophils and eosinophilia. A CT scan demonstrated mediastinal lymphadenopathies, liver enlargement and splenomegaly. An excisional biopsy of a cervical lymph node demonstrated findings consistent with a diagnosis of T-cell lymphoblastic lymphoma. Bone marrow aspirate and biopsy revealed hypercellular marrow with granulocytic predominance, left-shifted granulopoiesis, eosinophilia and the cytogenetic analysis showed the following karyotype: 46, XY, t(8;13). The final diagnosis was a myeloproliferative syndrome with eosinophilia related to t(8;13) and T-cell acute lymphoblastic lymphoma (8p11 myeloproliferative syndrome). We review the relevant literature about this unusual entity.

A Case of Angioimmunoblastic T-cell Lymphoma Hidden in Plain Sight: A Delay in Diagnosis and Management

Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon type of cluster of differentiation (CD)4 T-cell peripheral lymphoma. The varied clinical presentations of AITL present a challenge for accurate diagnosis. We present a case of a 57-year-old female with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, who presented to the hospital in the summer of 2021 with shortness of breath for 3 months. She underwent an extensive workup for lymphadenopathy while in Canada involving multiple core lymph node biopsies, which were inconclusive. Here in our institution, several tests for infectious diseases were unremarkable. Imaging tests revealed bilateral pleural effusion, lymphadenopathies, and rectal thickening. Results from rectal biopsy and excisional cervical lymph node biopsy revealed findings typical of AITL. Due to worsening hypoxia with pleural fluid accumulation, bilateral chest tubes (PleurX catheter) were placed. Steroids and chemotherapy were started. She was discharged in stable condition to follow-up care. An integrated and persistent approach comprising clinical, morphologic, excisional biopsy, immunophenotyping, and molecular tests is essential in reaching a correct diagnosis of AITL. Through our consistent effort to obtain further imaging and tissue biopsies, we came to the diagnosis which allowed her to begin appropriate life-saving treatments.

A258 ROSAI-DORFMAN0-DESTOMBES DISEASE: A RARE CAUSE OF OBSTRUCTIVE JAUNDICE

BackgroundRosai-Dorfman-Destombes Disease (RDD) is rare histiocytic disorder that is most frequently seen in children and young adults. Gastrointestinal involvement is reported in <1% of cases and typically involves the small bowel and colon. Pancreatic and hepatic involvement has been previously reported but is extremely rare.AimsTo describe a case of obstructive jaundice in the setting of a very rare histiocytic disorder known as RDD.MethodsCase ReportResultsA 59-year old previously healthy male of Asian descent presented with obstructive jaundice. Initial imaging demonstrated intra and extrahepatic biliary duct dilation with concurrent diffuse enlargement of the pancreas compatible with autoimmune pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) was performed with stenting and biopsy. ERCP demonstrated a distal common bile duct stricture with biopsies suggestive of low grade reactive changes and inflammation. Subsequent endoscopic ultrasound (EUS) guided biopsy of the pancreas showed active and chronic inflammation, necrosis, and atrophic pancreatic tissue, with no definitive evidence of autoimmune pancreatitis (Figure 1). Ca-19-9 and IgG4 were normal. He was treated with a course of prednisone and responded well, with repeat CT imaging showing almost complete resolution of the previously demonstrated pancreatic changes. A diagnosis of autoimmune pancreatitis was made. He re-presented 6-months later, however, with fatigue and repeat imaging now displayed lymphadenopathy in the neck, chest, and abdomen, and a bulky pancreatic head with associated hepatomegaly. Lymph node excisional biopsy confirmed the diagnosis of RDD with the presence of scattered histiocytic cells showing emperipolesis with a low number of IgG4 positive cells (Figure 1). The patient was promptly initiated on prednisone and rituximab and has since then had excellent clinical response.ConclusionsRDD is a rare non-Langerhans cell histiocytosis of unknown etiology that has a prevalence of 1:200 000. RDD clinically presents with painless bilateral cervical lymphadenopathy and can manifest with both nodal and extra nodal involvement. The most common sites of extra nodal disease are the skin and central nervous system, but rarely, can also present with pancreatic involvement. The use of fine needle guided biopsy in diagnosing RDD with extra nodal disease can be limited by low yield, sclerotic tissue, or non-diagnostic findings. For this reason, RDD with pancreatic involvement can masquerade as autoimmune pancreatitis, pancreatic malignancy and IgG4-related disease.This case report raises awareness about RDD with pancreatic and biliary involvement, a rare entity, that can present with obstructive jaundice. Figure 1: Histological sections of lymph node(left) with hystiocytic cells showing emperipolesis(arrow) and pancreas(right) showing active and chronic inflamation, necrosis and atrophyFunding AgenciesNone

Resolving the heterogeneous tumor-centric cellular neighborhood through multiplexed, spatial paracrine interactions in the setting of immune checkpoint blockade.

Direct interactions between tumor and immune cells mediate the antitumor effect of all modern cancer immunotherapeutic agents. Simultaneously, tumor cells have evolved mechanisms of evasion including the downregulation of HLA-I potentially disrupting the mechanism of action employed by many immune checkpoint inhibitors. And yet the in situ interplay between these cells within the tumor immune microenvironment (TIME) remains elusive. Recent advances in histologic multiplex bioimaging platforms have enabled in-depth molecular characterization of single cells within spatially-preserved and clinically archived tumor tissues. Herein, we applied multiplex immunofluorescence (MxIF) to excisional lymph node biopsies from 14 patients with metastatic melanoma who experienced clear objective responses to immunotherapy (7 complete response; 7 progressive disease) to determine distinguishing features of the TIME in the pretreatment setting. Distinct regions of the TIME were evaluated using 35 proteins probing tumor, immune and vasculature components across 323 fields of view. Single cell compositional analysis confirmed established prognostic immune cell types including increased prevalence of cytotoxic T cells within the tumor core FOVs of responders. Integrating single cell quantification with the spatial arrangement of cellular neighborhoods surrounding tumor cells revealed novel, spatial immune signatures capable of stratifying TIME based on clinical response. Our analysis revealed dynamic cellular composition of the TCCN based on anatomical subregion, functional expression of HLA-I by the index tumor cell and ultimately clinical response to immunotherapy. Overall, this study provides an analytical framework to resolve the cellular complexity of the TIME, increasingly relevant to the outcomes of modern cancer immunotherapy.

Kikuchi Fujimoto Disease: A Case Report with Literature Review

Kikuchi-Fujimoto disease (KFD), also referred to as histiocytic necrotizing lymphadenitis, is an uncommon entity, usually benign, self-limiting disease characterised by fever and regional lymphadenopathy of unexplained aetiology. There is an increase in reported cases of KFD, particularly in Asia. It is important to recognize this condition because it may be confused for systemic lupus erythematosus (SLE), tuberculosis or lymphoma. The knowledge of this condition among clinicians and pathologists can help to avoid misdiagnosis and inappropriate treatment. It must be considered among the differential diagnoses of cervical lymphadenopathy. Here, we present a case of 20-year-old male who came to the hospital with complaints of mild fever, chills, fatigue and cervical lymphadenopathy. After radiological investigations an excisional biopsy of the cervical lymph node was done and the diagnosis of KFD was confirmed. Due to the paucity of cases in literature, reporting this case may help shed light on this rare disease.

Multiparameter immunohistochemistry analysis of HIV DNA, RNA and immune checkpoints in lymph node tissue

The main barrier to a cure for HIV is the persistence of long-lived and proliferating latently infected CD4+ T-cells despite antiretroviral therapy (ART). Latency is well characterized in multiple CD4+ T-cell subsets, however, the contribution of regulatory T-cells (Tregs) expressing FoxP3 as well as immune checkpoints (ICs) PD-1 and CTLA-4 as targets for productive and latent HIV infection in people living with HIV on suppressive ART is less well defined. We used multiplex detection of HIV DNA and RNA with immunohistochemistry (mIHC) on formalin-fixed paraffin embedded (FFPE) cells to simultaneously detect HIV RNA and DNA and cellular markers. HIV DNA and RNA were detected by in situ hybridization (ISH) (RNA/DNAscope) and IHC was used to detect cellular markers (CD4, PD-1, FoxP3, and CTLA-4) by incorporating the tyramide system amplification (TSA) system. We evaluated latently infected cell lines, a primary cell model of HIV latency and excisional lymph node (LN) biopsies collected from people living with HIV (PLWH) on and off ART. We clearly detected infected cells that coexpressed HIV RNA and DNA (active replication) and DNA only (latently infected cells) in combination with IHC markers in the in vitro infection model as well as LN tissue from PLWH both on and off ART. Combining ISH targeting HIV RNA and DNA with IHC provides a platform to detect and quantify HIV persistence within cells identified by multiple markers in tissue samples from PLWH on ART or to study HIV latency.

Postoperative recurrence with right cervical lymph node metastasis in hepatocellular carcinoma: a case report

BackgroundHepatocellular carcinoma (HCC) patients with metastases to the cervical lymph nodes are extremely rare, and its clinical course is characterized by rapidly progressive disease. Hence, there have been no reports of metastatic cervical lymph node recurrence indicated after a long postoperative surveillance period.Case presentationThe patient was a 63-year-old male who underwent right hepatectomy for HCC of the right upper lobe. Three years after resection, metastatic lymph node recurrence was detected in the subdiaphragm, superior mediastinum, and right cervical lymph nodes. The patient underwent excisional biopsy of the cervical lymph node, followed by molecular-targeted therapy and radiation therapy. Lenvatinib reduced the size of all metastatic lymph nodes and the patient survived for a relatively long period of 43 months after the recurrence was detected.ConclusionsAfter resection of HCC in the right upper lobe, there is the possibility of metastatic lymph node recurrence in unusual sites, including the cervical region, and lenvatinib may be effective in those recurrences.

Curative Intent Surgery of Oral Malignant Melanoma and Regional Lymph Node Biopsy Assessment in 25 Dogs: 2006-2017.

Medical records were searched for dogs that had received curative intent surgery for oral malignant melanoma and ipsilateral excisional regional lymph node biopsy. Twenty-seven dogs were operated on and 25 dogs of these dogs met the inclusion criteria of signalment, post-excision margin status, presence of metastasis for each biopsied lymphocentrum, survival time post-excision, presence of recurrence or metastasis at follow-up or at death/euthanasia, location of the primary tumor, and any postoperative adjuvant treatment. These 25 dogs had complete tumor excision with tumor-free margins and 19 (76%) had postoperative adjuvant therapy. Median survival time after excision for the dogs in this study was 335.5 days. Results of this study support previous work that documents prolonged survival time following complete excision of oral malignant melanoma with tumor-free surgical margins in dogs. Additionally, 4 dogs (16%) had histologically confirmed regional lymph node metastasis at the time of definitive surgery.

Disseminated lymph node tuberculosis after splenectomy: an unusual case report in an adolescent

BackgroundSplenectomized patients are at an increased risk for overwhelming post-splenectomy infections typically with encapsulated bacteria. The clinical association between splenectomy and lymph-node tuberculosis is unclear.Case presentationWe describe a rare case of disseminated tuberculous lymphadenitis in an 18-year-old woman with history of splenectomy because of hereditary sherocytosis. She was admitted with enlargement of bilateral-cervical and left-axillary lymph nodes and fever. A diagnosis of probable tuberculosis was made based on the findings of fine-needle aspiration. Histology showed granulomas and extensive caseous necrosis, with the site of puncture located at an enlarged lymph node on the right side. The diagnosis was confirmed via nucleic-acid amplification tests following excisional biopsy of the left axillary lymph node. Disseminated tuberculous lymphadenitis was localized in the bilateral neck, right lung hilum, left sub-axillary region, and mediastinum, as detected from contrast-enhanced computed tomography of the neck.ConclusionsMycobacterium tuberculosis infection should be considered in children and adolescents with extensive enlargement of lymph nodes after splenectomy.

Four PAX5 Negative Nodular Sclerosing Hodgkins Lymphoma Case Series

Abstract Introduction/Objective Hodgkins lymphoma is a B cell lymphoproliferative disease, with most cases showing PAX5 positivity. Very few PAX5 negative hodgkins lymphoma cases have been described. We describe four PAX5 negative nodular sclerosing hodgkins lymphoma cases. All received standard chemotherapy, three received additional chemotherapeutic agents. Exploring these rare cases can be invaluable in characterizing and later treating his atypical presentation. Methods/Case Report Four cases of Hodgkins Lymphoma were diagnosed between 2017 and 2020. Two males and two females between 31 and 80 year old. Case 1 was a 31 year old male with a left neck lymphadenopathy that revealed nodular sclerosing Hodgkins lymphoma without bone marrow involvement. IHC staining revealed CD15, CD30, fascin and MUM-1 positivity, and PAX5 negativity. He received Doxorubicin, Vinblastine, Dacarbazine (AVD) and Brentuximab with radiation, and later brentuximab with bendamutine. Follow up PET-CT and left axillary node excisional biopsy found nodular sclerosing classic hodgkins. He received Ifosfamide, Carboplatin, and Etoposide. Case 2 was a 37 year old male with bilateral mediastinal lymphadenopathy that demonstrated nodular sclerosing Hodgkins lymphoma on biopsy. The cells were CD15, CD30 positive, and PAX5 negative. He received AVD with bleomycin (ABVD), and field radiation with excellent response and is currently under surveillance. Case 3 was a 31 year old female with a left chest mass that demonstrated nodular sclerosing Hodgkins lymphoma. The cells were positive for MUM1, CD30 and fascin and negatively for CD15 and PAX5. She received ABVD. Case 4 was an 80 year old female with prior stage IV gastric diffuse large B cell lymphoma treated with Rituximab, Cyclophophamide, Vincristine, and Prednisone and achieved remission. She later developed neck masses that were biopsied revealing classic Hodgkins lymphoma. The cells stained for CD30, for CD15, and were negative for PAX5. She was started on AVD and is on palliative care. Results (if a Case Study enter NA) NA Conclusion Most hodgkins lymphomas are PAX5 positive. We found four cases of PAX5 negative Hodgkins lymphoma. Incidentally, all were of the nodular sclerosing subtype. All cases were treated with recommended chemotherapy and/or radiation. All four cases had good response with reduction in disease burden. This finding suggests that PAX5 negativity still allows the nodular sclerosing hodgkins lymphoma to be responsive to standard treatment modalties.

Cluster of Differentiation 274 Antigen Immunohistochemical Expression in Tumor and Peri-tumor Cells of Hodgkin and Non-Hodgkin Lymphoma and Clinicopathological Relation (Single-center Study)

BACKGROUND: Cluster of differentiation 274 (CD274) antigen has been investigated in tumors to evaluate its regulation and effect as a predictive of targeted therapy. Its expression and effect in lymphoma have raised interest recently. However, results were mixed and showed wide variations. AIM: This study aims to explore and compare CD274 antigen immunohistochemical expression in tumor and peri-tumor cells of classic Hodgkin lymphoma (HL) and diffuse large B cells non-HL (NHL) and its relation with clinicopathological criteria. METHODS: This work was carried out on 78 cases of lymph node excision biopsy (48 HL and 30 NHL). Prepared sections were applied for immunohistochemistry using CD274 monoclonal rabbit anti-human (programmed cell death protein 1 [PD-L1] ZR3-ASR, a Sigma Aldrich company). Assessment of CD274 antigen in tumor cells was considered positive if detected in &gt;10% (membranous staining with cytoplasmic accentuation). Peri-tumor cells were scored as: 0, no positive cells/high-power field (HPF); 1, &lt;10 positive cells/HPF; 2, 10–30 positive cells/HPF; 3, &gt;30 positive cells/HPF. RESULTS: CD274 antigen was expressed in 53.8% of total lymphoma cases with significantly more expression of CD274 antigen in HL than NHL (66.7% vs. 33.3%). Classic HL showed significantly higher expression of CD274 antigen in tumor and peri-tumor cells and significant association with elevated erythrocyte sedimentation rate and lactate dehydrogenase and male gender. INTERPRETATION AND CONCLUSION: There is a more frequent and significant expression of CD274 antigen in classic HL than NHL cases in tumor and peri-tumor cells and a significant association with bad prognostic criteria in classic HL. High expression of CD274 antigen in classic HL proposes its potential use as a marker, especially for prognostic indication.

Preoperative ultrasound accurately characterizes surgically confirmed extracranial spinal accessory nerve injuries.

To determine the accuracy of preoperative ultrasound and MRI in surgically confirmed spinal accessory nerve injuries and present the benefits of a multimodality image review. A retrospective review of 38 consecutive patients referred to a peripheral nerve surgical practice at an academic teaching hospital with surgically confirmed spinal accessory nerve injuries. All cases were reviewed for patient demographics, date and cause of injury, preoperative EMG, and surgical diagnosis and management. Additionally, prospective interpretation of preoperative ultrasound and MRI reports were reviewed for concordance or discordance with the surgical diagnosis. Iatrogenic injury was present in 37 (97%) cases and most commonly a result of an excisional lymph node biopsy (68%). Surgically confirmed spinal accessory nerve injury diagnoses consisted of 25 (66%) stump neuromas and 13 (34%) incomplete nerve injuries. Nine months was the average time from injury to surgery. Twenty-nine patients underwent preoperative ultrasound and/or MRI evaluation: 12 ultrasound only, 10 MRI only, and seven with both ultrasound and MRI. Eighteen (95%) preoperative ultrasound reports compared to four (24%) preoperative MRI reports were concordant with the surgical diagnosis. In the seven cases with both preoperative ultrasound and MRI, six had discordant ultrasound and MRI imaging diagnoses for which the ultrasound was concordant with the surgical diagnoses in all cases. Preoperative ultrasound more accurately characterizes spinal accessory nerve injuries compared to MRI and should serve as the modality of choice when a spinal accessory nerve injury is suspected.

A RARE CASE OF CRYPTOCOCCUS NEOFORMANS BY PLEURAL BIOPSY

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Cryptococcus are an opportunist fungal pathogen that can lead to life threatening infections usually in immunocompromised individuals, however it is rare in those who are immunocompotent. This case report presents a patient who came in with non-specific symptoms and generalized lymphadenopathy with a diagnosis of cryptococcus with pleuroscopy. CASE PRESENTATION: A 47 year old female with a past medical history of hypothyroidism and previous COVID 19 infection presents with weight loss, generalized lymphadenopathy and shortness of breath to a tertiary care center. Initial work up including chest imaging showed a right sided pleural effusion. Further imaging via computed tomography of the chest showed a free flowing moderate to large pleural effusion and right sided pleural thickening. This effusion was drained without complication, which showed an exudative etiology. Cultures and cytology from the pleural fluid showed were non diagnostic. Although the patient had a comprehensive infectious work up, and biopsy of a lymph node, both were non diagnostic for an infectious or malignant etiology. A pleuroscopy was performed, which showed multiple white deposits along the inferior portion of the right lung and the diaphragm, which were biopsied. These biopsies grew cryptococcus neoformans, with further history correlating with cave exploration and exposure to endemic fungi. DISCUSSION: Cryptococcus grows readily in soil contaminated with bird excretions, and is transmitted via inhalation of the contaminated aerosol. Here, we presented a rare case of Cryptococcal infection diagnosed via pleuroscopy and pleural biopsy. The patient had blood cultures, respiratory cultures, gram stain, along with culture data from pleural fluid which showed no growth. Furthermore, the patient also had testing via Cryptococcal antigen, which was negative. The patient had no known immunodeficiency condition such as HIV, diabetes, renal failure, liver failure, use of steroids, or other immunosuppressive drugs. Furthermore, the patient had excisional lymph node biopsies which ruled out malignancy. The aim of this report is to utilize pleuroscopy and pleural biopsy in those patients with a high likelihood of an infectious etiology with pleural disease. CONCLUSIONS: Cryptococcal meningitis should be a diagnostic consideration even when dealing with meningitis in immunocompetent patients. Cryptococcal antigen test can help us clinch the diagnosis in time though culture would be a better diagnostic tool if available. However, in the setting of this test being negative, and other non diagnostic infectious work up, biopsy of the pleura involved can aid in the diagnosis of a fungal infection if the likelihood is high. REFERENCE #1: Curi AL, Lazera M, Vasconcelos-Santos DV: Cryptococcosis. In Intraocular Inflammation.Springer, Berlin, Heidelberg.2016;1277–1283. 10.1007/978-3-540-75387-2_123 DISCLOSURES: No relevant relationships by Selvin Jacob, source=Web Response No relevant relationships by Pushan Jani, source=Web Response

NO RHEUM FOR AIR: MIXED CONNECTIVE TISSUE DISEASE PRESENTING AS INTERSTITIAL LUNG FIBROSIS IN A YOUNG WOMAN

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Interstitial Lung Disease(ILD) is a serious complication of Mixed Connective Tissue Disorder(MTCD) associated with high morbidity and mortality. We describe an unusual case of a young patient presenting with advanced fibrosis at the time of initial diagnosis of MTCD. CASE PRESENTATION: A 39 year old female presented with dyspnea and dry cough of four months duration that progressively worsened requiring assistance for daily activities. She had associated weight loss, night sweats, diffuse arthralgia without any swelling and right hand stiffening. She denied any fevers, oral/nasal ulcers, vision changes, recent travel, tick bites, skin rash, smoking, household mold or pets. Physical examination revealed bibasilar crackles and mild dusky appearance of fingers. Laboratory investigations showed a normal blood count, elevated d-dimer and inflammatory markers. High Resolution Computerized Tomography(HRCT) Scan of the chest showed diffuse ground glass opacities, subpleural reticulation/scarring, traction bronchiectasis with multiple areas of honeycombing as well as extensive mediastinal lymphadenopathy. The serological panel was significant for high titers of Anti-Nuclear Antibodies(ANA) 1:1280 speckled pattern with low complement C3/C4 level, Rheumatoid Factor(RF) 138, Immunoglobulin G(IgG) 5000, anti-SSA and anti-ribonucleoprotein antibodies 133 and 148 respectively, elevated aldolase and creatinine kinase. Infectious workup was negative. The diffusely positive serology and lymphadenopathy was concerning for lymphoma. However, the excisional lymph node biopsy was negative for malignancy and showed changes consistent with autoimmune etiology. She was diagnosed with MTCD with features of lupus, sjogrens, rheumatoid arthritis, myositis presenting as ILD. Treatment with steroids and hydroxychloroquine was initiated with improvement in her respiratory symptoms. DISCUSSION: ILD in patients with MTCD ranges from being asymptomatic to advanced fibrosis with a high mortality rate.Typically, intial pulmonary function testing shows reduced diffusion capacity which progresses to restrictive pattern in the later stages along with HRCT changes. Our patient, although young, had rapid progression of pulmonary symptoms and was found to have advanced scarring on initial presentation. The diffusely positive serology can overlap with lymphoma and biopsy of lymph node/lung can give definite diagnosis. Since screening guidelines for MTCD-ILD are not clearly established any clinical symptoms should prompt further investigations. Treatment especially steroids during the acute inflammatory phase with ground glass opacities has good prognosis whereas the response is poor once signs of fibrosis develop. CONCLUSIONS: Advanced fibrosis ILD is an uncommon presentation of MTCD in a young patient. Early diagnosis and prompt initiation of therapy especially during the acute phase can prevent further progression of disease. REFERENCE #1: Narula N, Narula T, Mira-Avendano I, Wang B, Abril A. Interstitial lung disease in patients with mixed connective tissue disease: pilot study on predictors of lung involvement. Clin Exp Rheumatol. 2018 Jul-Aug;36(4):648-651. Epub 2018 May 8. PMID: 29745875 REFERENCE #2: Taha R, Feteih M. Pulmonary Manifestations of Connective Tissue Diseases. Skills in Rheumatology. 2020 Aug 29:139–75. doi: 10.1007/978-981-15-8323-0_7. PMCID: PMC7784640.? DISCLOSURES: No relevant relationships by Sana Hyder, source=Web Response No relevant relationships by Evan Nadler, source=Web Response No relevant relationships by Nikola Perosevic, source=Web Response No relevant relationships by Evan Wasserman, source=Web Response

BILATERAL INGUINAL LYMPHADENOPATHY AS THE EXTRAPULMONARY PRESENTATION OF PULMONARY SARCOIDOSIS: A RARE CLINICAL PRESENTATION

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Sarcoidosis is a multi-systemic granulomatous disorder of unknown etiology and is characterized pathologically by the presence of non-caseating granulomas in involved organs; particularly in the lungs, hilar lymph nodes, skin, and eyes. Sarcoidosis affects individuals of any age, sex and race but it commonly affects young to middle-aged, Black American adults. The diagnosis of sarcoidosis is made on the basis of clinical features with compatible radiological findings and is further supported by the histological evidence non-caseating granulomas in affected organs, and the exclusion of other disorders that may present similarly. Biopsy is usually recommended for all patients that are suspected of having sarcoidosis with the exception of Lofgren's syndrome, Heerfordt syndrome and Lupus Pernio. Extra-pulmonary lymph nodes are present in 15% of patient's at the time of diagnosis. We present a young female who presents with bilateral inguinal lymphadenopathy as the first sign of sarcoidosis CASE PRESENTATION: A 32 year old female presented with complaints of bilateral, non-tender, inguinal swellings that progressively enlarged over a two week period. This was accompanied by a five pounds weight loss which she attributed to decreased appetite due to personal stressors. She had no associated fever, chills, vaginal discharge, dyspnea, cough, arthralgia or rashes. Physical examination revealed multiple, palpable, non-tender, mobile inguinal lymph nodes of varying sizes bilaterally with no associated overlying skin changes. She had no hepatomegaly, splenomegaly or uveitis. The erythrocyte sedimentation rate was 34 mm/hr (<25 mm/hr), 25 hydroxy-vitamin D was 13.5 ng/mL (30.0-80.0 ng/mL) and serum angiotensin converting enzyme level was 259 U/L (9.0-47.0 U/L). Abdomen and pelvic computed tomography showed bilateral inguinal lymphadenopathy measuring up to 1.6 cm on short axis. Chest computed tomography showed bulky mediastinal and bilateral hilar adenopathy with bilateral axillary lymphadenopathy. There were multifocal clusters of peri-lymphatic lung nodules in bilateral lungs. Excisional biopsy of the right inguinal lymph node revealed non-caseating granulomatous lymphadenitis. Acid fast bacilli (AFB) stain was negative for acid fast organisms. DISCUSSION: While extra-pulmonary manifestations of sarcoidosis are common, inguinal lymphadenopathy remains a rare presenting complaint with few documented cases. This finding suggests that biopsy of peripheral lymph nodes in an effort to establish the presence of granulomas, with the appropriate radiographic findings and clinical presentation, remains a viable and minimally invasive method of diagnosing sarcoidosis. CONCLUSIONS: The differential diagnosis for inguinal lymphadenopathy should include systemic conditions such as sarcoidosis. REFERENCE #1: Baughman, RP, Teirstein, AS, Judson, MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164: 1885–1889. REFERENCE #2: Monnet P, Thevenon J. Sarcoidosis with clinically isolated mediastinal adenopathy; diagnosis confirmed by biopsy of inguinal & right pre-scalenic lymph nodes. Lyon Med 1959;91:191-5. REFERENCE #3: Iannuzzi MC, Rybicki BA, Teirstein AS (2007) Sarcoidosis. N Engl J Med 357(21):2153–2165. DISCLOSURES: No relevant relationships by Sai Achi, source=Web Response No relevant relationships by Raji Ayinla, source=Web Response No relevant relationships by Janet Joseph, source=Web Response No relevant relationships by Richard Sheppard, source=Web Response