Admixed Lymphocytes Research Articles

Immunoreactivity of Histiocytes to OCT4; a diagnostic pitfall

Abstract Introduction/Objective Immunohistochemical stains are supposed to make a Pathologists’ life easier; however, interpretation of some stains in isolation can be a diagnostic pitfall. Immunoreactivity of paraganglia to OCT4 stain is a known pitfall for this stain when evaluating retroperitoneal lymph node dissection specimens for germ cell tumour metastasis. The purpose of this report is to highlight another pitfall of the OCT4 stain, albeit in a similar clinical scenario. Methods/Case Report A 49-year-old male with a history of left testicular seminoma metastatic to periaortic, retroperitoneal and left supraclavicular lymph nodes, status post orchiectomy and chemotherapy, presented with a rising B-HCG and PET scan evidence of recurrent/refractory disease. His imaging showed interval increase in FDG uptake of left periaortic lymph nodes despite a decrease in size. A biopsy was performed. Pathologic evaluation showed predominantly necrotic tissue with rare clusters of atypical cells with clear to pink cytoplasm, monotonous nuclei, and rare admixed lymphocytes. Immunohistochemical stains showed the atypical cells to be positive for OCT4 stain, raising the possibility of viable seminoma. However, additional satins showed the cells to be positive for CD68 and CD163, and negative for CD117, SALL-4, pancytokeratin, SF-1, GATA3 and synaptophysin. Therefore, the atypical cells were interpreted to represent histiocytes; no viable germ cell tumor was identified. Results (if a Case Study enter NA) NA Conclusion This case highlights the importance of using a panel of immunohistochemical stains, instead of relying on one stain, even if the stain is thought to be fairly specific. Pathologists need to be aware of immunoreactivity of histiocytes to OCT4 as a potential diagnostic pitfall in addition to the paraganglion cells staining for OCT4 being a pitfall.

Intrathyroid thymic carcinoma/carcinoma showing thymus-like elements (CASTLE): An extremely rare presentation of thyroid malignancy

Intrathyroid thymic carcinoma, also known as carcinoma showing thymus-like elements/CASTLE, is an uncommon malignancy that arises in the thyroid gland. This tumour shares both morphological and immunohistochemical characteristics with thymic carcinomas. Preoperative diagnosis can be challenging as the clinical and histological features may mimic other high-grade thyroid malignancies. Differentiating CASTLE from other thyroid lesions is important as it has a better prognosis.A 46-year-old man presented with progressive dysphagia, difficulty in breathing and cough for eight months. The ultrasound scan (USS) revealed a hypoechoic lesion in the right lobe of the thyroid. The cytology specimen obtained through non-US-guided fine needle aspiration (FNA) was reported as Thy5/Bethesda VI, consistent with papillary thyroid carcinoma and a total thyroidectomy was performed. Macroscopic examination revealed a white, non-encapsulated tumour in the right lobe of the thyroid, measuring 45x40x25 mm, with gross extrathyroidal extension. Microscopically, this lesion predominantly showed a squamous morphology with admixed lymphocytes. The tumour cells tested positive for CD5, CD117, CK5/6, CK19 and synaptophysin, and were negative for TTF1 and calcitonin, confirming its classification as CASTLE.This case brings attention to the difficulties encountered in diagnosing uncommon lesions in both cytology and histology and emphasizes the crucial contribution of immunohistochemistry in navigating through such complex scenarios.

Tre-P-27 - Cutaneous T-cell lymphoma of mycosis fungoides type with CD30 positive transformation and sweet like neutrophilic dermatosis

<h3>Introduction:</h3> Cutaneous lymphomas are malignancies of T- or B-cell origin, with the majority of cases of approximately 75% being cutaneous T-cell lymphomas (CTCL). The main subtype of CTCL include the most frequent mycosis fungoides (MF), accounting for approximately 60% of CTCL. Mycosis fungoides is most often indolent but patients with advanced disease and especially transformed disease with large atypical, often CD30+ lymphocytes have a poor prognosis. The association of neutrophilic dermatosis (ND) with various hematologic disorders is well documented but uncommon with CTCL. <h3>Case report:</h3> An 80 years old woman was admitted for fulminant MF associated to Sweet-like ND not responding to systemic corticosteroids and methotrexate. Clinical symptoms (fever, painful skin nodules) and laboratory parameters (lymphocytosis and neutrophilia) were compatible with Sweet syndrome. Skin histology demonstrated dense, atypical lymphocytic infiltrate and numerous admixed lymphocytes. However, edema in the upper dermis, which is a histological hallmark of Sweet syndrome, was never present in the skin biopsies. After establishing diagnosis of transformed CD30+ MF with concomitant Sweet-like ND, treatment with Brentuximab was initiated and resulted in initial remission with reduction of mSWAT down to 30% from June 2020 to November 2020. However, after 6 cycles of Brentuximab, the MF progressed with new nodular ulcerated lesions, fierce itching and severe skin tenderness. Further, the disease was complicated by a superinfection and sepsis driven by methicillin resistant staphylococcus aureus, and later on pseudomonas aeruginosa. The MF related Sweet-like ND aggravated, paralleled by an overall decrease in the patient's condition. Chemotherapy was contraindicated in the context of infectious complications and deteriorated general condition. As a therapeutic alternative, we initiated a palliative radiotherapy, however, there was a fulminant disease progression and the patient deceased shortly after. <h3>Conclusion:</h3> The association of MF with ND is rare, underreported and seems to be related to poorer prognosis, resistance to treatment and impaired quality of life.

S1535 Unusual Cause of Biliary Obstruction in a Post Liver Transplant Patient

INTRODUCTION: Biliary obstruction is not an uncommon phenomenon after liver transplantation. Common bile duct structuring (CBD) at the surgical anastomosis or ischemic stricturing are more common causes. We describe a delayed cause of biliary obstruction from a post transplant lymphoproliferative disorder of the transplanted liver. CASE DESCRIPTION/METHODS: 65 years old female with history of alcoholic/NASH cirrhosis/HCC status post kidney/liver transplantation 2 years ago presented with one week of pruritus, nausea, vomiting and abnormal liver and kidney tests. She was on mycophenolate 250 mg po BID, prednisone 5 mg daily and tacrolimus of 2 mg twice daily for immunosuppression. Physical examination was unremarkable on presentation. Labs showed creatinine of 2.6 from base line of 1.8. Alkaline phosphatase of 895 from base line of 131. AST/ALT 82/201. Total bilirubin was 1.7 on presentation. On subsequent days, creatinine peaked to 8 and bilirubin increased to 9.7. Liver ultrasound showed a heterogeneous echogenicity in the region of the porta hepatis along with mild intrahepatic biliary ductal dilatation and normal caliber CBD. MRI/MRCP showed infiltrative hepatic hilar mass with mild biliary obstruction. PET scan revealed an FDG avid central hepatic soft tissue mass. ERCP showed long region of hilar stenosis with dilation of left hepatic ducts. It was not possible to pass a guide wire through the stenosis and place a stent. EUS guided biopsy of the liver mass was done, but sample was not enough for diagnosis. A percutaneous transhepatic drainage tube was placed by interventional radiology to relieve the obstruction and percutaneous biopsy of the liver mass was done. The biopsy demonstrates a population of plasma cells and admixed lymphocytes and histiocytes involving the soft tissue around biliary type ducts. In situ hybridization for Epstein Barr virus showed scattered positive cells. CD3 and CD20 highlight scattered T and B cells respectively. Proliferation index of 30 - 40%.. Finding were consistent with Polymorphic Post-transplant lymphoproliferative disorder (PTLD). Patient was started on R-CHOP regimen chemotherapy. Renal function test improved with hydration. DISCUSSION: The principal risk factors for the development of a PTLD are the degree of immunosuppression and the EBV serostatus. An accurate diagnosis of PTLD requires a high index of suspicion. A tissue biopsy, preferably an excisional biopsy, with review by an expert hematopathologist, is required to ensure an accurate diagnosis.Figure 1.: MRI of abdomen- showing infiltrative hilar mass with biliary obstruction.Figure 2.: PET scan- Infiltrative heterogeneous FDG avid central hepatic mass.Figure 3.: ERCP-long region of hilar stenosis with dilation of left hepatic ducts.

Successful Identification of Nasopharyngeal Carcinoma in Nasopharyngeal Biopsies Using Deep Learning.

Pathologic diagnosis of nasopharyngeal carcinoma (NPC) can be challenging since most cases are nonkeratinizing carcinoma with little differentiation and many admixed lymphocytes. Our aim was to evaluate the possibility to identify NPC in nasopharyngeal biopsies using deep learning. A total of 726 nasopharyngeal biopsies were included. Among them, 100 cases were randomly selected as the testing set, 20 cases as the validation set, and all other 606 cases as the training set. All three datasets had equal numbers of NPC cases and benign cases. Manual annotation was performed. Cropped square image patches of 256 × 256 pixels were used for patch-level training, validation, and testing. The final patch-level algorithm effectively identified NPC patches, with an area under the receiver operator characteristic curve (AUC) of 0.9900. Using gradient-weighted class activation mapping, we demonstrated that the identification of NPC patches was based on morphologic features of tumor cells. At the second stage, whole-slide images were sequentially cropped into patches, inferred with the patch-level algorithm, and reconstructed into images with a smaller size for training, validation, and testing. Finally, the AUC was 0.9848 for slide-level identification of NPC. Our result shows for the first time that deep learning algorithms can identify NPC.

A Rare Case of Intravascular Large B-Cell Lymphoma

First reported in the literature in 1959, intravascular large B-cell lymphoma (IVLBCL) is a very rare subtype of large cell lymphoma characterized by the proliferation of clonal atypical lymphocytes within the lumina of small blood vessels, without any obvious extravascular tumor mass or readily observable circulating lymphoma cells in the peripheral blood. The surprising degree of sparing of the surrounding tissue and the absence of lymphoma cells in the lymph nodes and reticuloendothelial system are a hallmark of the disease. Here were present a case of a 63-year-old female, without any significant medical history, presenting with a macule on the left breast skin. A punch biopsy was performed, which on histology revealed atypical lymphoid cells (large cells with vesicular nuclear chromatin and prominent nucleoli) within the smaller blood vessels in the reticular dermis. There was no infiltration of these atypical cells in the surrounding dermis. With a strong suspicion of lymphoma, the first round of immunohistochemistry was performed, which showed negative results for CK7, CK20, mammaglobin, CD31, and CD68 and strong positivity for CK20, suggestive of IVLBCL. Second round of immunostains was positive for CD79a, MUM1, and BCL-2; CD10 was negative while CD3 showed admixed lymphocytes, supportive of the diagnosis. IVLBCL is a rare disease with an estimated incidence of less than one per million. Median age of incidence is 70 years (34–90 years). Patients present with a variety of constitutional and systemic symptoms (especially CNS involvement) caused by the occlusion of small vessels, but our patient did not present with any. Skin involvement can manifest as nodules/plaques (49%), macules (22.5%), telangiectatic patches (20%), and cellulitis. We present this rare and interesting case to highlight the existence of this entity since it carries a poor prognosis and requires a timely rituximab-containing chemotherapy plus CNS-oriented therapy.

Diagnostic Approach to Fine Needle Aspirations of Cystic Lesions of the Salivary Gland.

Fine needle aspiration (FNA) has diagnostic and therapeutic value in the management of salivary gland cysts. Rendering an accurate diagnosis from an aspirated salivary gland cyst is challenging because of the broad differential diagnosis, possibility of sampling error, frequent hypocellularity of specimens, morphologic heterogeneity, and overlapping cytomorphology of many cystic entities. To date, there have been no comprehensive review articles providing a practical diagnostic approach to FNA of cystic lesions of salivary glands. This article reviews the cytopathology of salivary gland cysts employing 2017 World Health Organization terminology, addresses the accuracy of FNA, and presents The Milan System approach for reporting in cystic salivary gland cases. The utility of separating FNA specimens from salivary gland cysts, based upon the presence of mucin and admixed lymphocytes in cyst fluid is demonstrated. A reliable approach to interpreting FNA specimens from patients with cystic salivary gland lesions is essential to accurately determine which of these patients may require subsequent surgery.

Microscopic background changes in brains of cynomolgus monkeys.

Brain sections from control cynomolgus monkeys (Macaca fascicularis) used in toxicology studies were evaluated retrospectively in order to better understand spontaneous background changes in this species. Hematoxylin and eosin-stained slides from 76 animals (38 males and 38 females) of 9 studies were examined. Eleven animals (9 males and 2 females) were each observed to have 1 to 3 findings within the brain sections examined, for a total of 19 findings. No findings were noted in the spinal cord. The most common finding was focal to multifocal perivascular infiltration of mononuclear cells, affecting the parenchyma, the meninges, or the choroid plexus. Additionally, focal gliosis was observed in 6 animals and a single focus of hemosiderin deposition (coincident with focal gliosis and mononuclear cell infiltrate) was noted in 1 animal. Most of the glial foci were composed of cells consistent with microglial cells, with or without admixed lymphocytes. All findings were of slight or minimal severity, lacked an apparent cause, and were considered incidental and of negligible biologic significance. An awareness of the spontaneous incidence of these background findings may facilitate the discernment of toxicologically relevant effects when these findings are observed.

Xanthogranulomatous Salpingitis Associated with a Large Uterine Leiomyoma

A case of xanthogranulomatous salpingitis (XGS) associated with a large uterine leiomyoma in a 50-year-old woman is presented. Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to affected organs. It is characterized by the presence of lipid-filled macrophages with admixed lymphocytes, plasma cells, and neutrophils. A review of the literature revealed that most patients with XGS have a clinical history of long-standing pelvic inflammatory disease (PID) or, less often, endometriosis. We report a case lacking a history of either PID or endometriosis but with a concurrent large uterine leiomyoma. Although the exact etiology in this case was not clear, the leiomyoma may have played a contributory role in pathogenesis.

Lymphocyte-Depleted Thymic Remnants

The head and neck region is a frequent site for potentially confusing incidental benign findings not related to the primary pathologic process and having no impact on patient prognosis. Several lesions are thymic in origin. We report 3 cases of lymphocyte-poor thymic remnants identified in central cervical (level VI) lymph node dissections for unrelated benign and malignant pathology. In each, the rests were nearly completely composed of bland epithelial cells with rare admixed lymphocytes. These cells were immunophenotypically similar to thymic epithelial cells, although they differed in the paucity of associated thymic lymphocytes and lack of Hassall corpuscles. Lymphocyte-depleted thymic remnants in the central cervical compartment are not well described in the literature. It is important to be aware of these and other benign inclusions to avoid making incorrect diagnoses of malignancy.

Extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum

We report a rare case of extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum. A 72-year-old Japanese man was admitted to our hospital presenting with a 3-mo history of epigastric pain, vomiting and weight loss. On computed tomography (CT) a wall thickening of the fourth part of the duodenum was observed. Multiple biopsies obtained from the lesion showed infiltration of plasma cells and lymphocytes, but they were not conclusive. The patient underwent resection of the lesion and, on histopathological examination, the lesion consisted of a dense and diffuse infiltrate of plasma cells and a few admixed lymphocytes with reactive follicles extending to the muscular propria. An extensive deposition of amyloid was also observed. Immunohistochemical stains revealed that a few plasmacytoid cells showed lambda light chain staining, though most were kappa light chain positive. These cells also were positive for CD138 and CD56 but negative for CD20 and CD79. The findings were consistent with extramedullary plasmocytoma associated with a massive deposit of amyloid in duodenum. A subsequent workup for multiple myeloma was completely negative. The patient showed no signs of local recurrence or dissemination of the disease after 12 mo follow-up. Because of the association of plasmocytoma and amyloidosis, the patient must be followed up because of the possible systemic involvement of the neoplasm and amyloidosis in future.

Deep “Benign” Fibrous Histiocytoma: Clinicopathologic Analysis of 69 Cases of a Rare Tumor Indicating Occasional Metastatic Potential

Benign fibrous histiocytoma (FH) is one of the most common mesenchymal neoplasms of the skin. Several histologic variants of cutaneous FH have been described, some of which also have distinct clinical features including a propensity for local recurrence. Deep benign FH is an uncommon and poorly recognized clinical subtype that arises in subcutaneous or deep soft tissue. Only a single small series of these neoplasms has been published, and their clinical behavior is not well characterized. In this study, we report the clinicopathologic features of 69 deep FH retrieved from our consultation files. The patients included 41 males and 28 females, ranging in age from 6 to 84 years (median, 37 y). The most common anatomic location was the extremities (58%); the remainder arose on the head and neck (22%), trunk (11%), and in the deep soft tissue of the retroperitoneum, mediastinum, or pelvis (9%). All lesions arising in nonvisceral soft tissue were subcutaneous. The tumors ranged from 0.5 to 25 cm in size (median, 3.0 cm) and were well circumscribed grossly and microscopically. All tumors were composed of bland ovoid to spindle cells arranged in a storiform pattern with admixed lymphocytes. Multinucleate giant cells, osteoclastic giant cells, and/or foam cells were present in 59% of cases, whereas the other 41% were cytologically monomorphic, often resembling cellular FH. Other common findings included a hemangiopericytomalike vascular pattern (42%) and stromal hyalinization (39%). Four cases were classified as atypical deep FH due to the presence of scattered markedly pleomorphic spindle cells within an otherwise histologically typical lesion. The median mitotic rate was 3/10 HPF; 10 cases (14%) had >10 mitoses/10 HPF. Necrosis (2 cases) and lymphovascular invasion (1 case) were rare. Immunohistochemistry revealed expression of CD34 in 20/50 cases (40%), smooth muscle actin in 15/40 (38%), and focal desmin in 1/12 (8%). Of the 37 patients for whom clinical follow-up was available (median, 40 mo), 8 (22%) had a local recurrence; in all 8 cases, the tumor had been marginally or incompletely excised. Metastases occurred in 2 patients (5%), both of whom ultimately died of disease; however, this number is likely exaggerated due to consultation bias. The metastasizing tumors were large (6 and 9 cm) and 1 had tumor necrosis but they were otherwise histologically identical to the nonmetastasizing lesions. In summary, deep FH has many histologic features in common with cutaneous cellular FH; however, it usually has a more diffusely storiform pattern than the latter, is well circumscribed, and may have striking hemangiopericytomalike vessels. Similar to the cellular, aneurysmal, and atypical variants of FH, deep FH recurs in approximately 20% of cases and may rarely metastasize.

Xanthogranulomatous salpingitis and oophoritis: a case report and review of the literature.

A case of xanthogranulomatous salpingitis and oophoritis in a 47-year-old woman is presented. Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to affected organs; it is characterized by the presence of lipid-filled macrophages with admixed lymphocytes, plasma cells, and neutrophils. Only a few cases of xanthogranulomatous salpingitis and oophoritis have been reported to date. The case presented here is associated with Escherichia coli infection, endometriosis, and an intrauterine device.

Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages.

A recent immunohistochemical analysis of the Aschoff lesions in rheumatic fever, combining immunohistochemical analysis with comparative morphology, permitted the division of the Aschoff nodules into three stages: (1) Aschoff nodule without admixed lymphocytes, (2) Aschoff nodules with a few T lymphocytes, and (3) Aschoff nodules containing many admixed lymphocytes of both B- and T-cell phenotype. It was postulated that the order of progression was from stage 1 with macrophages only, to accumulation of first T lymphocytes (stage 2) and then B lymphocytes (stage 3). This study was undertaken to determine the role and distribution of interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor alpha (TNF alpha) in the various stages of the rheumatic Aschoff nodule to investigate our hypothesis on the progression of these nodules. Sixteen fresh valve specimens from patients with acute rheumatic fever undergoing valve surgery were obtained. Tissue sections from 14 specimens identified as containing Aschoff nodules were subjected to immunohistochemistry for (1) T and B lymphocytes, to stage the lesions according to our previously proposed criteria; (2) IL-1, IL-2 and TNF alpha; and (3) CD4 and CD8 to phenotype the T lymphocytes. The stage 1 and 2 lesions expressed IL-1 and TNF alpha in the macrophages. The stage 3 lesions showed more variable expression of all three cytokines including IL-2 within T lymphocytes. TNF alpha and IL-1 secretion in macrophages is required for T and B lymphocytes activation and aggregation; suggesting that macrophages arrive at the scene of rheumatic injury prior to the lymphocytes. IL-2 is usually expressed later in the inflammatory process and was found only in the lymphoid aggregates. This study therefore produces corroborative evidence for our previously proposed developmental stages of the Aschoff nodule.

Evidence for specific annexin I-binding proteins on human monocytes.

Recombinant human annexin I and a monoclonal antibody specific for this protein (mAb 1B) were used to investigate surface binding of this member of the annexin family of proteins to peripheral blood monocytes. Flow cytometric analysis demonstrated trypsin-sensitive, saturable binding of annexin I to human peripheral blood monocytes but not to admixed lymphocytes. A monoclonal antibody that blocks the anti-phospholipase activity of annexin I also blocked its binding to monocytes. These findings suggest the presence of specific binding sites on monocytes. Furthermore, surface iodination, immunoprecipitation and SDS/PAGE analysis were used to identify two annexin I-binding proteins on the surface of monocytes with molecular masses of 15 kDa and 18 kDa respectively. The identification and characterization of these annexin I-binding molecules should help us to better understand the specific interactions of annexin I with monocytes that lead to down-regulation of pro-inflammatory cell functions.