Node Biopsy Specimens Research Articles

Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 μg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

Kikuchi‐Fujimoto disease presenting with papular lesions on the elbows and knees

Kikuchi-Fujimoto disease is a self-limited febrile lymphadenitis of unknown etiology, possibly associated with cutaneous lesions. We report a case of Kikuchi-Fujimoto disease presenting with papular lesions limited to the elbows and knees. The skin biopsy specimen showed spongiosis and pseudo-Pautrier abscesses in addition to the typical histopathological findings of Kikuchi-Fujimoto disease. Although necrosis was not observed in the lymph node biopsy specimen, histopathological and immunohistochemical findings were consistent with Kikuchi-Fujimoto disease in the proliferating phase. Kikuchi-Fujimoto disease (KFD) is a self-limited febrile lymphadenitis of unknown etiology, predominantly affecting the cervical lymph nodes of young adults.1 Nodal lesions show paracortical necrosis with non-neutrophilic karyorrhexis, infiltration of CD8+ T cells and myeloperoxidase (MPO)+ histiocytes, and CD123+ plasmacytoid dendritic-cell clusters, although necrosis may be absent depending on the disease phases.1, 2 Cutaneous lesions have been reported in up to 40% of cases.3 The skin manifestations are variable, but often present on the upper body.4-6 We report a case of KFD with papular lesions limited to the elbows and knees. A 20-year-old man presented with a 2-week history of fever. Physical examination revealed non-tender lymphadenopathy of bilateral posterior cervical, axillary, and inguinal lymph nodes and non-pruritic erythematous papules on the elbows and knees (Figure 1A,B). Laboratory tests showed elevated levels of C-reactive protein (3.62 mg/dL) and serum lactate dehydrogenase (318 U/L; reference range, 124–222 U/L) and decreased white blood cell count (1700/μL). Anti-nuclear antibodies were negative. Computed tomography did not detect central lymph node swelling. The skin biopsy specimen showed interface dermatitis, papillary dermal edema, and dermal infiltrate (Figure 1C). In the epidermis, spongiosis and pseudo-Pautrier abscesses were present (Figure 1D). The dermal lymphohistiocytic infiltrate was associated with karyorrhexis in the absence of neutrophils (Figure 1E). Most lymphocytes were positive for CD3 and contained both CD4+ and CD8+ cells, although most of the intraepidermal T cells were CD8+ cells expressing TIA1, perforin, and granzyme B. The dermal infiltrate contained numerous CD68+ (clones KP-1 and PG-M1) histiocytes (Figure 1F) that were comprised of CD163+, MPO+, and CD123+ cells. The lymph node biopsy specimen showed paracortical lymphohistiocytic infiltrate with karyorrhexis in the absence of neutrophils (Figure 1G). CD8+ T cells predominated over CD4+ cells (Figure 1H,I). CD68+, CD163+ histiocytes were abundant, and most of them expressed MPO (Figure 1J,K). Clusters of CD123+ plasmacytoid dendritic cells were present (Figure 1L). Although necrosis was not observed in the lymph node biopsy specimen, the diagnosis of KFD in the proliferative phase was made based on the histopathological and immunohistochemical findings.1, 2, 4-6 Only supportive therapies with an oral non-steroidal anti-inflammatory drug and topical corticosteroid were given. Fever, lymphadenopathy, and cutaneous lesions resolved spontaneously in 5 weeks after the disease onset. Cutaneous lesions of KFD are characterized by superficial and deep dermal lymphohistiocytic infiltrate, non-neutrophilic karyorrhexis, interface dermatitis, and papillary dermal edema.4-6 Although spongiosis was observed in some cases,5, 6 presence of pseudo-Pautrier abscesses has not been reported. The reason why the cutaneous lesions in our case were limited to the elbows and knees is unknown, but their localization and the spongiotic epidermal changes suggest involvement of exogenous stimuli. Differential diagnosis of KFD mainly includes SLE and lymphomas.1 In our case, serum anti-nuclear antibodies were negative, and clinical signs suggestive of SLE other than fever and lymphadenopathy were absent. Histopathological and immunohistochemical findings of skin and lymph node biopsy specimens excluded both SLE and lymphomas. In patients with cutaneous eruptions, fever, and lymphadenopathy, KFD should be considered. Immunohistochemical studies are useful for accurate diagnosis, especially in atypical cases. We thank K. Gunshin for her technical assistance. The authors declare no conflict of interest. Approval of the research protocol: N/A. Informed consent: Written informed consent was obtained from the patient. Registration No. of the study/trial: N/A. Animal studies: N/A. The data that support the findings of this study are available from the corresponding author, K.K., upon reasonable request.

CD5- and CD10-positive MYC and BCL2 double-expressor diffuse large B-cell lymphoma with MYD88L265P mutation: a case report and literature review

A 75-year-old man who had lymphadenopathy was admitted to our hospital. Histopathological examination of cervical lymph node biopsy specimens showed diffuse proliferation of lymphoma cells with large nuclei. In immunohistochemistry, the lymphoma cells were positive for CD5, CD10, CD20, BCL2, BCL6, and MYC. The patient was diagnosed with CD5- and CD10-positive diffuse large B-cell lymphoma (DLBCL). MYD88L265P mutations have been detected in DLBCL. Partial response was achieved after six courses of R-THP-COP therapy. However, the patient died because of disease progression 18 months after the diagnosis. On autopsy, lymphoma cells were found in the lymph nodes throughout the body, central nervous system, adrenals, and skin. CD5- and CD10-positive DLBCL account for 0.5-1% of DLBCL cases and have a very poor disease prognosis. This is a rare case of CD5- and CD10-positive DLBCL with MYC and BCL2 expressions harboring MYD88L265P mutation.

Lymph Nodes With Increased IgG4-positive Plasma Cells and Patterns Suspicious for IgG4-related Disease: Can Lymph Nodes Be the Only Site of Disease?

Lymphadenopathy with increased immunoglobulin (Ig) G4 + plasma cells can be a nonspecific finding or a manifestation of immunoglobulin G4-related disease (IgG4-RD). It remains unclear whether there are characteristic pathologic features of IgG4-RD involving lymph nodes, or if IgG4-RD lymphadenopathy can occur without other manifestations of IgG4-RD. In this study, we assessed 55 lymph node biopsy specimens (44 men and 11 women with a mean age of 55y) with increased IgG4 + plasma cells that had 1 of the 6 well-described pathologic patterns. We also correlated these findings with IgG4 serum levels and followed these patients for 7 to 108 months (mean, 34.9mo) for the occurrence of extranodal IgG4-RD. We further compared lymphadenopathy in patients who developed other manifestations of IgG4-RD (RD + , n=20, 36%) versus those who did not (RD - , n=35, 64%). We found that there were only minor significant differences between 2 groups, including frequency of receiving treatment (RD + , 90% vs. RD - , 60%, P =0.021) and higher serum levels of C-reactive protein (>8mg/L, RD + , 53% vs. RD - , 13%, P =0.007). Other differences were either borderline or not significant, including mean age (RD + , 59.8y vs. RD - , 51.9y, P =0.097), male-to-female ratio (RD + , 16:4 vs. RD - , 28:7, P =1), constitutional symptoms (RD + , 25% vs. RD - , 9%, P =0.096), multiple enlarged lymph nodes (RD + , 45% vs. RD - , 26%, P =0.143), good response to therapy (RD + , 94% vs. RD - , 94%, P =1); higher serum IgG4 levels (>280mg/dL, RD + , 75% vs. RD - , 51%, P =0.086), anemia (RD + , 45% vs. RD - , 43%, P =0.877), leukopenia (RD + , 0% vs. RD - , 3%, P =0.446), thrombocytopenia (RD + , 10% vs. RD - , 6%, P =0.556), positivity for antinuclear antibody (RD + , 24% vs. RD - , 29%, P =0.688), elevated serum levels of lactate dehydrogenase (>225U/L, RD + , 0% vs. RD - , 20%, P =0.064), elevated serum IgE level (>100IU/mL, RD + , 75% vs. RD - , 92%, P =0.238), and hypergammaglobulinemia (RD + , 90% vs. RD - , 86%, P =0.754). There were also no differences in morphologic patterns ( P =0.466), IgG4 + cell location ( P =0.104), eosinophil counts (RD + , 10.3±11.3 vs. RD - , 13.4±17.5, P =0.496), Epstein-Barr virus positivity (RD + , 35% vs. RD - , 60%, P =0.074), and Epstein-Barr virus-positive cell location ( P =0.351). Our findings suggest that there are minimal differences between stringently defined IgG4-RD lymphadenopathy with versus without other manifestations of IgG4-RD. These findings also suggest the existence of IgG4-RD lymphadenopathy as the sole presentation of IgG4-RD.

Bilateral mydriasis as first manifestation of Hodgkin’s lymphoma: a case report

BackgroundBilateral mydriasis is usually associated with severe brain stem damage or drug-induced sympathomimetic stimulation.Herein we report it as a unique neurologic complication of Hodgkin’s lymphoma.Case presentationA 23-year-old woman presented at our emergency department with dilated pupils unresponsive to light stimuli. MRI and CT scans showed bilaterally enlarged lymph nodes in the mediastinum and supraclavicular compressing the carotid artery on both sides. The histologic examination of lymph node biopsy specimens confirmed the diagnosis of Hodgkin’s lymphoma.ConclusionPathologies around the carotid artery causing oculosympathetic spasm should be considered among the possible causes of a mydriasis, especially when other common causes like brain stem impairment are excluded.

Belatacept-Based Maintenance Immunosuppression Controls the Post-Transplant Humoral Immune Response in Highly Sensitized Nonhuman Primates.

Preexisting donor-specific antibodies (DSA) to MHC antigens increase the risk of antibody-mediated rejection (AMR) in sensitized transplant recipients and reduces graft survival. Pretransplant desensitization with costimulation blockade and proteasome inhibition has facilitated transplantation in our preclinical nonhuman primate (NHP) model. However, long-term graft survival is limited by rebound of DSA after transplantation. In this study, we performed kidney transplants between highly sensitized, maximally MHC-mismatched NHPs (n=14). At kidney transplantation, primates received T cell depletion with rhesus-specific anti-thymocyte globulin (rhATG; n=10) or monoclonal anti-CD4 and anti-CD8 antibodies (n=4). Maintenance immunosuppression consisted of belatacept and tacrolimus (n=5) or belatacept and rapamycin (n=9) with steroids. Rebound of DSA post-kidney transplantation was significantly reduced compared with maintenance immunosuppression with tacrolimus, mycophenolate, and steroids. Protocol lymph node biopsy specimens showed a decrease in germinal center activity, with low frequencies of T follicular helper cells and class-switched B cells after kidney transplantation. Combined belatacept and rapamycin was superior in controlling viral reactivation, enabling weaning of ganciclovir prophylaxis. Tacrolimus was associated with increased morbidity that included cytomegalovirus and parvovirus viremia and post-transplant lymphoproliferative disorder. All primates in the tacrolimus/belatacept group failed discontinuation of antiviral therapy. Overall, belatacept-based immunosuppression increased AMR-free graft survival by controlling post-transplant humoral responses in highly sensitized NHP recipients and should be further investigated in a human clinical trial.

EZH1-PRC2 Identifies a Potential Reservoir for Disease Relapse in Quiescent Cancer Cells Refractory to EZH2 Enzymatic Inhibition

Recurrent disease relapse and remission is a hallmark of indolent non-Hodgkin lymphoma (NHL). Remissions are often characterised by long periods of clinical inactivity without detectable disease. Furthermore, it is now standard practice to clinically monitor carefully selected asymptomatic patients with indolent lymphoma, often for years, reserving therapy for symptomatic disease progression, without adversely affecting the patient's prognosis. Identification and targeting of the putative cellular reservoir recurrently seeding disease relapse and progression in NHL has long tantalised researchers and would represent a significant advance in the field given the hypothetical prospect of deferring or preventing impending relapse. The oncogene EZH2 is upregulated in the lymphoid germinal center and forms the enzymatic core of Polycomb Repressive Complex 2 (PRC2) alongside essential core components EED and SUZ12, writing all methylation of H3K27, with H3K27me3-mediated silencing of the B-cell terminal differentiation programme. The EZH2 small molecule enzymatic inhibitor Tazemetostat has been approved as monotherapy beyond second line for relapsed/refractory EZH2-mutant and wild-type follicular lymphoma, with responders benefiting for a modest median duration of 10.9 months (Morschauser et al., Lancet Oncology, 2020). The mechanism(s) for disease progression in patients have not yet been published. Using TIG3-T human diploid fibroblasts as a model of cellular quiescence, we discover that a novel form of PRC2 predominates in non-dividing cells, which contains EZH1, EED, SUZ12 and the polycomb-like protein, PHF1, but crucially lacks EZH2. RNA-Seq and Western blot analysis revealed reciprocal expression patterns of EZH1 and EZH2 in serum-starved, quiescent (non-dividing) cells compared to asynchronous cycling cells. Using EED immunoprecipitation with subsequent mass spectrometry, we demonstrated that EZH1 replaces EZH2 as the predominant H3K27 methyltransferase in quiescent cells. Quantitative ChIP-sequencing with exogenous reference genome spike-in (ChIP-Rx) confirms that EHZ1-PRC2 largely replaces EZH2-PRC2 at polycomb target genes. While the EZH2 enzymatic inhibitor GSK343 and the EED allosteric inhibitor A395 significantly reduced H3K27me2 and H3K27me3 in cycling cells, those markes are unchanged in quiescent cells. This alludes to a function of EZH1-PRC2 in quiescent cells that is independent of its function as a H3K27 methyltransferase, and therefore not targetable by PRC2 enzymatic inhibitors. The EED PROTAC UNC6852 degrades EED (Figure 1), thereby destabilising both EZH1-PRC2 and EZH2-PRC2, as confirmed by Western blot and ChIP-Rx. Strikingly, this molecule resulted in a marked reduction of H3K27me2 and H3K27me3 in proliferating cells, but had no such effect in treated quiescent cells. Degradation of PRC2, however, did result in a modest reduction in protein levels and chromatin occupancy of the canonical PRC1 component CBX7, suggesting an interplay between EZH1-PRC2 occupancy and local cPRC1-mediated chromatin of compaction of Polycomb target genes. EZH2 and Ki-67 immunohistochemistry and EZH1 RNA in situ hybridization (RNA-ISH) were performed on lymph node biopsy specimens from two well-matched patients with histological grade 2 follicular lymphoma (Figure 2). Patient 1 has multiply relapsed follicular lymphoma, rapidly requiring therapy following this biopsy. Patient 2 presented with a right inguinal mass and stage 3A disease, though did not require therapy for 14 years from the time of this biopsy. Interestingly, while both patients harbour abundant EZH1-positive cells (approximately 60% of cells within neoplastic follicle), only patient 1 whose tumour expressed abundant EZH2 and Ki-67 had clinically active disease requiring therapy. Although this requires validation in a larger series, these cases illustrate the presence of lymphoma cells in both patients likely to be refractory to PRC2 enzymatic inhibitors in vivo. In summary, we propose that EZH1-PRC2 delineates a non-proliferating, PRC2 enzymatic inhibitor-resistant population of cells that could serve as a disease reservoir in indolent NHL. These cells are targetable by PROTAC-mediated EZH1-PRC2 degradation, with the resultant disruption reflecting the non-enzymatic roles of EZH1-PRC2. EZH1-PRC2 should be addressed as a therapeutic target to treat NHL in the future. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

63 (PB-063) Poster - Is sentinel lymph node biopsy without frozen section in early stage breast cancer sufficient in accordance with ACOSOG-Z0011? A retrospective review from King Chulalongkorn Memorial Hospital

Background: In 2021, there is an increased global trend for sending sentinel lymph node biopsy (SLNB) specimens for permanent section (PS) without intraoperative frozen sections (FS). ACOSOG Z0011 revealed that reoperation of axillary lymph node dissection (ALND) was not necessary in patients with 1 or 2 nodal metastases. Permanent section alone was thought to be sufficient for sentinel lymph node (SLN) diagnosis. This pilot study conducted in Thailand determines the re-operation rate for SLNB without FS.

Is sentinel lymph node biopsy without frozen section in early stage breast cancer sufficient in accordance with ACOSOG-Z0011? A retrospective review from King Chulalongkorn Memorial Hospital

BackgroundIn 2021, there is an increased global trend for sending sentinel lymph node biopsy (SLNB) specimens for permanent section (PS) without intraoperative frozen sections (FS). This pilot study conducted in Thailand determines the re-operation rate for SLNB without FS.MethodWe retrospectively reviewed 239 SLNB cases without FS at King Chulalongkorn Memorial Hospital from April 2016 to April 2021. The patients were diagnosed with primary invasive breast cancer with clinically negative nodes. The clinical nodal status was assessed from physical examination. The re-operation rate was determined by the number of positive SLNs; where 3 more nodal metastases were subjected to a second surgical procedure.ResultBetween April 2016 and April 2021, 239 patients who had undergone SLNB in accordance with ACOSOG Z0011 criteria with PS alone was enrolled. A total of 975 SLNs were removed from these 239 patients, with an average of 4.15 nodes per patient. Out of 239 patients, 21 (8.8%) and 6 (2.5%) had metastatic disease in 1 and 2 nodes, respectively. The remaining 212 (88.7%) patients had no nodal metastasis. None of the patients were subjected to a second surgical procedure.ConclusionWe conclude that the implementation of SLNB with PS analysis alone in patients who satisfy the ACOSOG Z0011 criteria, with a re-operation rate of 0%, does not have outcomes that would be altered by the standard of care additional FS analysis. With ommision of FS analysis, operation cost, operative time and anesthetic side effects are projected to decrease.

Correlation between physical characteristics of biopsy specimen and disease of cervical lymph node after contrast-enhanced ultrasound

BackgroundTo investigate the correlation between physical characteristics and disease of cervical lymph node biopsy specimens after contrast-enhanced ultrasound.MethodsAll patients were biopsied after CEUS, 235 patients were divided into three groups A, B and C according to the physical characteristics of specimens: 92 patients in group A were complete tissue specimens; 113 patients in group B were discontinuous tissue specimens. There were 30 patients in group C, including a small number of tissue and floc, purulent and bloody specimens. Pathological examination, pathogen culture examination and Gene X-Pert MIB examination were completed for all patients in the three groups, and statistical analysis was conducted on the integrity and traits of the specimens.ResultsGroup A included 92 intact tissue specimens, 21 with reactive hyperplasia, 17 with lymphoma, 12 with metastatic carcinoma, 13 with lymphadenopathy, 15 with necrotizing lymphadenitis, and rare lymphadenopathy. In group B, 113 patients were treated with intermittent tissue specimens, including infected lymph nodes, lymphoma in 1 case, metastatic carcinoma in 3 cases and sarcoidosis in 1 case. There were 30 patients in group C, including a small amount of tissue and floc, purulent and bloody specimens, all of which were infected lymph nodes. The χ2 value of malignant and benign lymph nodes was 42.401, p = 0.000.ConclusionThe physical characteristics of cervical lymph node biopsy specimens after CEUS are correlated with the disease, which has guiding significance for postoperative specimen selection.

Association of pSTAT3, pSyk with c-Myc, p53, BCL2 proteins expression and survival of patients with diffuse large B-cell lymphoma

Background . Diffuse large B cell lymphoma (DLBCL) is one of the most common non-Hodgkin’s lymphomas. The effectiveness of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone) therapy was observed in about 60 % of patients, in 20–30 % of cases DLBCL is characterized by a refractory course. Standard clinical prognostic criteria do not accurately determine the prognosis of the disease. In this regard, the problem of developing additional predictors of DLBCL course remains relevant today and is directly related to the molecular pathogenesis of the disease. The objective : to determine the relationship of pSTAT3, pSyk with c-Myc, p53, BCL2 oncoproteins expression and survival of DLBCL patients. Materials and methods . Biopsy specimens of lymph nodes and other organs and tissues obtained from 100 patients with newly diagnosed DLBCL were used for the study. All patients received standard first-line immunochemotherapy according to the R-CHOP regimen. Determination of the relative amount of tumor cells expressing pSTAT3, pSyk was carried out using immunohistochemical and morphometric methods. The threshold value of proteins expression was calculated using the ROC analysis: for pSTAT3 it was 68 % of positive tumor cells, for pSyk – 28 %. The relationship of pSTAT3, pSyk with c-Myc, p53, BCL2 expression was determined using the Pearson χ2 test. Overall (OS) and progression-free (PFS) survival were calculated using the Kaplan–Meier method (log-rank test). Results . The suprathreshold pSTAT3 expression was found to be associated with a high content of c-Myc and p53 transcription factors in tumor cells (p = 0.015 and p = 0.010, respectively). In the group of patients with isolated overexpression of pSTAT3, the 5-year OS and PFS were lower, and the risk of death and disease progression was almost 1.5 times higher than in patients with low protein expression (p = 0.015 and p = 0.011, respectively). When studying the co-expression of pSTAT3 and pSyk, the lowest OS and PFS were recorded in the subjects with a simultaneous high expression of these proteins. With this combination of markers, the probability of an adverse event in patients when calculating OS increased by 2.9 times (p = 0.003; hazard ratio 2.9; 95 % confidence interval 1.43–5.85), and when analyzing PFS – by 2.3 times (p = 0.021; hazard ratio 2.3; 95 % confidence interval 1.14–4.87) compared with other variants of their simultaneous expression. Conclusion . Overexpression of pSTAT3 is associated with unfavorable biological tumor characteristics and poor patient survival. The combined suprathreshold expression of the pSTAT3 and pSyk proteins is associated with lower OS and PFS values compared to their isolated expression.

Molecular Diagnosis of Cat Scratch Disease: a 25-Year Retrospective Comparative Analysis of Various Clinical Specimens and Different PCR Assays.

ABSTRACTCat-scratch disease (CSD), caused primarily by Bartonella henselae, is a common etiology of infectious regional lymphadenopathy. Lymphadenopathy is preceded by a primary inoculation lesion and may progress to suppuration. Laboratory diagnosis of CSD is hampered by the limitations of available confirmatory tests. PCR, in general, is highly sensitive and specific; however, clinical sensitivity in CSD varies greatly between studies. We aimed to identify clinical specimens and PCR assays best suited for CSD diagnosis using a national CSD registry and a uniform case definition. Different clinical specimens and PCR assays, including conventional and real-time PCR, were evaluated. PCR was positive in 335/390 (86%) CSD patients and 425/482 (88%) PCR tests. The highest PCR sensitivity was achieved in lymph node pus aspirates (96%; n = 278 tests) followed by primary lesions (88%; n = 50), lymph node fine needle aspirations (85%; n = 46), lymph node biopsy specimens (73%; n = 91) and paraffin-embedded lymph nodes (59%; n = 17), (P < 0.001). Sensitivity was similar in all types of PCR assays studied. PCR negative predictive value of pus aspirate and lymph node biopsy specimen patient groups was 82% and 72%, respectively. Specificity was 100% based on 125 non-CSD patients with negative PCR. In conclusion, the specimen type rather than the PCR assay type has a major impact on CSD molecular diagnosis. We assume that the inadequate sensitivity of the biopsy specimens was due to sampling errors or the presence of inhibitory factors. Primary lesions should be sampled more frequently for CSD diagnosis. Physicians should be aware of the low PCR negative predictive value of lymph node biopsy specimens.IMPORTANCE Polymerase chain reaction (PCR) for the detection of Bartonella henselae is an important tool for the diagnosis of cat scratch disease (CSD); however, clinical sensitivity varies greatly between studies. The current study shows that the specimen type, with pus aspiration, fine needle aspiration, and primary inoculation lesion having significantly higher sensitivity than fresh or formalin-fixed paraffin-embedded lymph node biopsy specimen, rather than the type of the PCR assay, whether a conventional or a real-time assay, has a major impact on the performance of diagnostic PCR for CSD. The new data provide new tools for the clinical microbiologist when interpreting the results of the PCR assays. Primary inoculation lesions, although easily accessible, are often neglected and should be sampled more frequently for molecular diagnosis of CSD. Physicians should be aware that negative PCR, particularly if performed on fresh or paraffin-embedded lymph node biopsy specimens, does not exclude CSD.

CHOLESTATIC JAUNDICE AS A CLINICAL PRESENTATION OF HODGKIN’S LYMPHOMA IN A 20-YEAR-OLD SAUDI MALE PATIENT, A CASE REPORT

Background: Hodgkin lymphoma (HL) represents approximately 10% of lymphomas and is curable in most, but not all, patients. It has a bimodal incidence, although it most commonly presents in young adults. Presentation with mediastinal, cervical, and supraclavicular involvement is particularly common for the nodular sclerosing subtype. Patients may also present with B symptoms, although that is more commonly seen in elderly patients with more advanced disease. Pruritus may also be a presenting symptom. The diagnosis is established with a lymph node biopsy specimen showing Reed-Sternberg cells, malignant cells that originate from germinal center B cells and are seen in an inammatory inltrate. Case Report: We report a case of a 20 years old Saudi male presented to our emergency department with jaundice without clinical lymphadenopathy, accompanied with laboratory investigations that is showing intrahepatic cholestasis. The patient was admitted initially to evaluate the causes of jaundice that he has mainly by investigating hepatic and post-hepatic diseases. Months later, he has developed palpable lymphadenopathy. Surgical excisional biopsy result concluded that the patient is having Hodgkin's lymphoma. Conclusion:Although it is thought to be an uncommon cause of intrahepatic cholestatic, lymphomas should be considered in evaluating a patient who came with similar presentation.

Morphologic Spectrum of Lymphadenopathy in Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced, adverse T-cell-mediated hypersensitivity reaction that most often involves skin. The pathologic findings of DRESS-related lymphadenopathy have been described infrequently in the literature. To present a case series of DRESS-related lymphadenopathy with an emphasis on the morphologic spectrum. We describe detailed clinical and pathologic findings along with the literature review. We focus on the differential diagnosis between DRESS lymphadenopathy and angioimmunoblastic T-cell lymphoma (AITL). There were 4 men and 1 woman with a mean age of 41 years (range, 23-59 years). One patient (20%) died. Three lymph node biopsy specimens showed a pattern reminiscent of AITL (AITL-like pattern) and 2 cases showed necrotizing lymphadenitis (Kikuchi-like pattern), associated with vasculitis in 1 case. The AITL-like morphology of DRESS-related lymphadenopathy may be difficult to distinguish from genuine AITL. The clinical information is important for differential diagnosis, including history of drug exposure, age, and the rarity or absence of AITL-associated manifestations such as hemolytic anemia and hypergammaglobulinemia. Molecular analysis of the T-cell receptor genes is helpful, typically revealing a polyclonal pattern in DRESS-related lymphadenopathy. In the literature, 4 histologic patterns of DRESS lymphadenopathy have been described: reactive lymphoid hyperplasia, necrotizing lymphadenitis, Hodgkin lymphoma-like, and AITL-like. These patterns, particularly those that resemble lymphoma, highlight the importance of correct diagnosis to avoid unnecessary therapies.

S2397 First Reported Case of Kikuchi-Fujimoto Disease in a Crohn’s Disease Patient

Introduction: Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare entity, mostly associated with autoimmune conditions such as SLE. It is benign, focal, self-limited, and despite abundant literature, its pathogenesis remains unknown. We report a unique case of KFD in a patient with coexisting Crohn’s disease. Case description/methods: A 23-year-old female with no medical history was evaluated for Iron deficiency anemia and anorexia. She underwent a colonoscopy which revealed normal colonic mucosa, however, an ulcerated and congested terminal ileum was seen. Biopsies were significant for acute cryptitis and granuloma. Serology was positive for anti–Saccharomyces cerevisiae antibody and fecal calprotectin was elevated. She was initially started on oral corticosteroids and later transitioned to azathioprine and Adalimumab, with a good response. 7 months later, she was planned for a repeat colonoscopy to check for endoscopic healing, however, at her pre-procedure COVID testing, she was noted to have rubbery painless LAD of the right neck. The procedure was postponed and she was immediately asked to discontinue her medications. She was referred to an oncologist. A CT chest was unremarkable and an excisional biopsy of the largest of the lymph node revealed necrotizing lymphadenitis, favoring KFD. Infectious workup was negative. Over the next 2 months, her LAD spontaneously resolved without the need for medications. A repeat colonoscopy was aborted due to poor prep. A follow-up MRE revealed long segment mid and distal Crohn's ileitis, and fecal calprotectin remained elevated. She was started on oral budesonide with plans to restart biological therapy after repeating a colonoscopy. Discussion: KFD may rarely involve the terminal ileum, potentially masquerading as Crohn’s disease. Our patient, however, had histological findings pathognomic for Crohn’s and her ileitis did not resolve with the resolution of LAD. Lymphoma remains a feared adverse outcome of both immunomodulators and Anti-TNF medications, thus necessitating their cessation upon signs of LAD. However negative EBV testing, an unrevealing chest CT, and a benign histological diagnosis of KFD may allow our patient to safely resume these medications to treat her Crohn's.Figure 1.: Excisional Lymph node biopsy specimen demonstrating necrotizing histiocytic lymphadenitis. No infectious organisms were identified (Negative PAS, Warthin-Starry stain, Tuberculosis, HSV 1/2 and EBV immunohistochemistry).

Hist-O-06 - Image-guided lymph node core-needle biopsy predicts survival in mycosis fungoides and Sézary syndrome

<h3>Background:</h3> The prognosis of Sézary syndrome (SS) and mycosis fungoides (MF) depends on lymph node (LN) involvement. The usefulness of LN image-guided core-needle biopsies (CNBs), instead of surgical sampling, has been poorly evaluated. <h3>Objectives:</h3> To determine the prognostic value of LN CNB in MF/SS. <h3>Methods:</h3> A retrospective search was conducted to identify all LN biopsy specimens of MF/SS between 2008 and 2019. Biopsies were staged according to the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer (ISCL/EORTC) criteria. We performed immunolabelling and determined the tumour clone frequency (TCF) by high-throughput sequencing of the T-cell receptor beta locus. <h3>Results:</h3> We included 119 consecutive biopsies from 100 patients, 45 with MF and 55 with SS. N1, N2 and N3 stages were diagnosed in 34 (29%), 26 (22%) and 59 (49%) cases, respectively. The TCF, Ki67 index, and percentage of cells positive for thymocyte selection-associated high mobility group box protein (TOX), programmed cell death protein 1 (PD1), killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) and cluster of differentiation (CD)30 were all positively correlated with the N stage. Median overall survival (OS) for N1/N2 vs. N3 patients was 42 months (range 26–not reached) vs. 14 months (range 5–30), respectively (p<0.001). In univariate analyses, an age >75 years, LN short-axis diameter >15 mm, N3 stage, presence of large-cell transformation, TOX >60%, PD1 >25%, Ki67 >30%, KIR3DL2 >15%, CD30 >10% and TCF >25% were identified as adverse prognostic factors. In multivariate analyses, only an age >75 years and Ki67 index >30% were associated with reduced OS. We developed a new prognostic index associating the N stage and the Ki67 index, which better discriminates N3 patients with poor prognosis. <h3>Conclusions:</h3> CNB allows an objective assessment of the LN involvement in MF/SS, relevant for staging and prognosis.

Indolent B-Lineage Precursor Populations Identified by Flow Cytometry and Immunohistochemistry in Benign Lymph Nodes.

In this retrospective study, we report a series of benign lymph nodes showing small populations of normal B-cell precursors characterized by flow cytometry and immunohistochemistry. Ten cases identified during clinical flow cytometry practice were retrospectively reanalyzed with particular attention to hematogone categorization and enumeration. Immunohistochemical staining was performed on five excisional lymph node biopsy specimens to characterize the morphologic correlate. Populations of hematogones ranging from 0.13% to 1.86% (median, 0.51%) of all viable leukocytes were demonstrated in 10 benign lymph node samples from eight different patients ranging in age from 17 to 45 years (median, 37.5). These hematogones showed a characteristic immunophenotype (CD19+/CD10+) and maturational pattern by flow cytometry, with progression from stage 1 (median, 0.03%) to stage 2 (median, 0.19%) to stage 3 (median, 0.26%) seen in all cases. Immunohistochemical staining on five excisional biopsy specimens demonstrated a distinct perisinusoidal distribution of CD10+/CD20+ cells with a subset of TdT+ cells, providing a morphologic correlate. To our knowledge, this is the first study to characterize distinct hematogone populations within benign lymph nodes by both flow cytometry and immunohistochemistry. Recognizing these normal B-cell precursor populations is important to avoid their miscategorization as a CD10+ B-cell neoplasm.

27573 A clinical decision tool to calculate probability of sentinel lymph node metastasis in cutaneous melanoma

Objective: Sentinel lymph node status is a strong prognostic indicator for patients with cutaneous melanoma and is used to select patients for adjuvant therapy. However, unnecessary sentinel lymph node biopsy (SLNB) specimens have substantial cost and morbidity burden. Previous attempts to predict SLNB outcomes have relied on single-institution data and/or gene expression testing. Here we present Expected Lymphatic Metastasis Outcome (ELMO; https://melanoma-sentinel.herokuapp.com/), the first personalized clinical decision-making tool developed using nationally representative data with clinically actionable probability thresholds.

Tumor-to-tumor metastasis of diffuse large B cell lymphoma to gastric adenocarcinoma via CXCL12 (SDF-1)/CXCR4 axis: a case report

BackgroundTumor-to-tumor metastasis is the rare phenomenon in which one tumor exhibits metastatic deposits from another. To the best of our knowledge, there has been no prior reported case of tumor-to-tumor metastasis of a diffuse large B cell lymphoma (DLBCL) to a primary gastric adenocarcinoma.Case presentationA 70-year-old man presented with chest discomfort. An echocardiogram showed the presence of a right ventricular tumor. A positron emission tomogram showed multiple foci of abnormal activity in right cervical lymph nodes, cardiac wall, and stomach. A right cervical lymph node biopsy specimen revealed histological features of DLBCL. An esophagogastroduodenoscopy showed a large circumferential ulceration on the gastric body. Subsequent biopsy revealed adenocarcinoma cells surrounded by infiltrating lymphoma cells. On immunohistochemical staining, lymphoma cells were positive for CXCR4 and adenocarcinoma cells were positive for CXCL12/SDF-1. The patient was treated with six cycles of R-CHOP chemotherapy regimen, resulting in a complete remission.ConclusionsThis patient’s case implies that the interaction between a chemokine and its receptor may be the underlying mechanism for the observed tumor-to-tumor metastasis. Specifically, our case would suggest an involvement of the CXCL12 (SDF-1)/CXCR4 axis in the observed metastasis of DLBCL to primary gastric adenocarcinoma.

Lymphadenopathy Associated With Neutralizing Anti-interferon-gamma Autoantibodies Could Have Monoclonal T-cell Proliferation Indistinguishable From Malignant Lymphoma and Treatable by Antibiotics: A Clinicopathologic Study.

Early recognition of adult-onset immunodeficiency associated with neutralizing anti-interferon gamma autoantibodies (anti-IFNγ Abs) remains difficult, and misdiagnoses have been reported. Although febrile lymphadenopathy is among the most common initial manifestations of this disorder, no comprehensive clinicopathologic analysis of lymphadenopathy in patients with anti-IFNγ Abs has been reported. Here, we describe 26 lymph node biopsy specimens from 16 patients. All patients exhibited concurrent disseminated nontuberculous mycobacterial infections, and 31% received a tentative diagnosis of lymphoma at initial presentation. We found 3 distinct histomorphologic patterns: well-formed granuloma (46%), suppurative inflammation or loose histiocytic aggregates (31%), and lymphoproliferative disorder (LPD, 23%). The latter shared some of the features of malignant T-cell lymphoma, IgG4-related disease, and multicentric Castleman disease. Half of the specimens with LPD had monoclonal T cells, and 33.3% were indistinguishable from angioimmunoblastic T-cell lymphoma as per current diagnostic criteria. All lymphadenopathy with LPD features regressed with antibiotics without administration of cytotoxic chemotherapy or immunotherapy. The median follow-up time was 4.3 years. Our study highlights the substantial challenge of distinguishing between lymphoma and other benign lymphadenopathy in the setting of neutralizing anti-IFNγ Abs. Increased vigilance and multidisciplinary discussion among clinicians and pathologists are required to achieve the most appropriate diagnosis and management.