Rosai-Dorfman Disease, Presenting as a Right Atrial Mass with Involvement of the Tricuspid Valve in a 54-Year-Old Woman.

BACKGROUND Sinus histiocytosis with massive lymphadenopathy (SHML), Rosai-Dorfman disease, or Rosai-Dorfman-Destombes disease (RDD), is a rare non-Langerhans cell of unknown etiology. This report is of a case of isolated SHML, or Rosai-Dorfman disease, presenting as a right atrial mass with involvement of the tricuspid valve in a 54-year-old woman. This case shows the challenges of diagnosing this condition in the heart and the challenges of treating this rare disease with the limited information on the efficacy of the treatment modalities. CASE REPORT A 54-year-old Asian woman presented to the Emergency Department with chest and right upper quadrant pain. Transthoracic echocardiogram and computed tomography angiography showed a right atrium mass at the level of the tricuspid valve, causing moderate-severe regurgitation. Partial tumor debulking with biopsies later showed pink-yellow soft tissue, with histopathology showing histiocytes demonstrating emperipolesis. The tumor was positive for CD68 and S100 and negative for CD1a, consistent with Rosai-Dorfman disease. Subsequently the patient received targeted therapy with cobimetinib, without worsening cardiac function or disease progression. CONCLUSIONS This case highlights the challenging histopathological diagnosis of SHML, or Rosai-Dorfman disease, particularly in non-lymphoid tissue, such as the heart. Obtaining tissue for diagnosis can be challenging in this organ. Treatment is challenging when the mass cannot be extracted completely, like in our case, because other forms of therapies are not well studied and warrant further investigation, such as cobimetinib, which is a MEK pathway inhibitor approved in 2022 by the US Food and Drug Administration for histiocytic neoplasms.

A Rare Case of Blastic Plasmacytoid Dendritic Cell Neoplasm Occurred in Postchemotherapy of Breast Cancer.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy that arises from plasmacytoid dendritic cells. BPDCN typically presents with skin lesions and may involve peripheral blood, bone marrow, lymph nodes, or extranodal sites. It usually arises de novo, and some BPDCN cases are associated with or develop into myeloid neoplasms. Here, we report a case of a 57-year-old female presenting with cervical lymphadenopathy and skin rashes during the COVID-19 pandemic in 2021 following multiple types of postmastectomy therapy for breast cancer. The patient was ultimately diagnosed with BPCDN by lymph node biopsy. To the best of our knowledge, this is the first case report of BPDCN occurring postchemotherapy of breast cancer.

Spinal Ganglioneuroma.

An otherwise healthy 57-year-old man presented with intermittent low back pain and was incidentally found to have a left-sided paraspinal mass invading the spinal canal and causing spinal cord compression. He underwent a T11-12 hemilaminectomy, facetectomy, and instrumented fusion for a gross total resection with a good clinical outcome. Pathology revealed the lesion to be a ganglioneuroma. Ganglioneuroma is a rare and interesting pathology. These tumors are benign peripheral neuroblastic tumors derived from the neural crest and found along the entire neuroaxis. Tumors come to clinical attention if they cause symptomatic compression of neural structures or are found incidentally on imaging. Additionally, as these tumors share a common lineage with pheochromocytomas, systemic symptoms can be observed resulting from secretion of vasoactive peptides. The pathologic diagnosis of ganglioneuroma is predominantly based on morphology.

Epstein-Barr virus-induced natural killer/T cell lymphoma arising in tonsil and cervical node tissue.

Infection with Epstein-Barr virus (EBV) has been linked to approximately 10%-15% of lymphomas diagnosed in the USA, including a small percentage of Natural Killer (NK)/T cell lymphomas, which are clinically aggressive, respond poorly to chemotherapy and have a shorter survival. Here, we present a case of a patient found to have EBV-induced NK/T cell lymphoma from a chronic EBV infection. While the EBV most commonly infects B cells, it can infect NK/T cells, and it is important for the clinician to be aware of the potential transformation to lymphoma as it is clinically aggressive, warranting early recognition and treatment. NK/T cell lymphoma is a unique type of non-Hodgkin's lymphoma that is almost always associated with EBV. The disease predominantly localises in the upper aerodigestive tract, most commonly in the nose.

A Rare Case of Histiocytic Sarcoma Secondary to Gastrointestinal Stromal Tumor in the Stomach: Transdifferentiation or Synchronicity?

Histiocytic sarcoma is a rare malignant histiocytic neoplasm composed of cells with morphologic and immunophenotypic features of mature tissue histiocytes. It occurs anywhere in the body and behaves aggressively. However, its etiology is unknown. Here, we report a 68-year-old female who developed histiocytic sarcoma following chemotherapy with imatinib (Gleevec) for gastrointestinal stromal tumor. Possible mechanisms of transdifferentiation from gastrointestinal stromal tumor to histiocytic sarcoma are discussed based on the features of our case and other two similar cases in the literature.

Glomangiopericytoma of the sphenoethmoid complex.

Sinonasal glomangiopericytoma is a rare sinonasal tumour accounting for less than. 5% of all sinonasal tumours. This tumour often presents as another, more common type of vascular lesion and is similarly prone to haemorrhage. The optimal treatment includes complete surgical resection. We, herein, present two such cases adding to the world literature of this rare tumour.

Extracranial Meningioma in the Scalp with Concurrent Steatocystoma.

This report documents a rare case of an extracranial meningioma on the posterior scalp without apparent dural connection. Additionally, a sebaceous steatocystoma of the anterior scalp presented alongside the meningioma. A steatocystoma localized to the scalp is also remarkably rare. To our knowledge, this is the first report documenting both an extracranial meningioma and a steatocystoma presenting concurrently on the scalp. A male patient in his thirties presented with a mass lesion on the scalp. A CT scan revealed one posterior scalp mass with no intracranial abnormalities. Post excision histologic examination confirmed an extracranial meningioma (meningothelial variant, WHO Grade I). A second anterior scalp mass, not revealed by CT scan, was discovered during surgery. It was excised and diagnosed as a steatocystoma. Meningiomas predominantly occur intracranially but, in some instances, may present as a standalone extracranial tumor without intracranial abnormalities. Because extracranial meningioma is uncommon, it may be overlooked during clinical diagnosis of scalp masses. We recommend that this neoplasm be routinely considered in the differential diagnosis of extracranial tumors. The discovery of another rare tumor-a steatocystoma located in immediate proximity on the scalp-is further remarkable. We briefly review relevant case reports and etiologies and consider a potential relationship between the two neoplasms. However, it remains more likely that the concurrence of these tumors in our patient was simply coincidental.

A Rare Case of Extracavitary Primary Effusion Lymphoma in the Bladder and Ureter.

Primary effusion lymphoma (PEL) is a rare and very aggressive large B-cell lymphoma usually presenting as serous effusions without a tumor mass. It is universally associated with human herpesvirus type-8 (HHV-8) infection. It most commonly occurs in the body cavities and rarely develops as solid tumor masses in the wall of cavity and other organs, and it has been termed as extracavitary PEL. Extracavitary PEL has been reported in the lymph nodes and extranodal sites. Here we report a rare case of extracavitary PEL occurring in the bladder and ureter of a human immunodeficiency virus (HIV)-negative 76-year-old Chinese male, presenting with right leg swelling, erythema, and pain. To the best of our knowledge, this is the first case of extracavitary PEL presenting in the bladder and ureter.

A case report of parotid mammary analogue secretory carcinoma and reviews.

INTRODUCTION: Mammary analog secretory carcinoma (MASC) is a new diagnosis of head and neck tumors first reported in 2010. It was often misdiagnosed as salivary acinic cell carcinoma (AciCC). We present a patient with an asymptomatic parotid tumor that underwent deep lobe parotidectomy and postoperative radiation therapy. The final pathology showed MASC. CASE PRESENTATION: A 57-year-old male presented with an asymptomatic enlarging right parotid mass. A CT neck with IV contrast showed a 1.2 cm heterogeneously enhancing mass in the center of the right parotid gland without extraparotid extension. An FNA showed an epithelial neoplasm with papillary features. The patient underwent a right deep lobe parotidectomy with facial nerve dissection. The final pathology confirmed the diagnosis of MASC. He subsequently completed a 6-week course of radiation therapy and remained asymptomatic at his 30-month follow up. DISCUSSION/CONCLUSION: Although MASC is considered a low-grade tumor in most cases, recurrence and disseminated disease are not uncommon. No standard treatment protocol has been established. This report aims to enhance the awareness of this diagnosis and provide a review of current treatments for head and neck oncology care providers.

Sebaceous lymphadenoma requiring superficial parotidectomy.

An 82-year-old woman presented with a painless, progressively enlarging right neck mass of 2 years' duration. CT with contrast showed a 5.0 cm confluence of nodes just inferior to the right parotid gland. Fine-needle aspiration showed a lymphoproliferative disorder. Incisional biopsy showed sebaceous lymphadenoma. She subsequently underwent superficial right parotidectomy with neck dissection of level II-V (performed for enlarged lymph nodes causing significant pain). Facial nerve was preserved. She remained free of disease nearly 1 year postoperatively.

Allergen Exposure in Lymphopenic Fas-Deficient Mice Results in Persistent Eosinophilia Due to Defects in Resolution of Inflammation.

Asthma is characterized by chronic airway type-2 inflammation and eosinophilia, yet the mechanisms involved in chronic, non-resolving inflammation remain poorly defined. Previously, our group has found that when Rag-deficient mice were reconstituted with Fas-deficient B6 LPR T cells and sensitized and challenged, the mice developed a prolonged type-2-mediated airway inflammation that continued for more than 6 weeks after the last antigen exposure. Surprisingly, no defect in resolution was found when intact B6 LPR mice or T cell specific Fas-conditional knockout mice were sensitized and challenged. We hypothesize that the homeostatic proliferation induced by adoptive transfer of T cells into Rag-deficient mice may be an important mechanism involved in the lack of resolution. To investigate the role of homeostatic proliferation, we induced lymphopenia in the T cell-specific Fas-conditional knockout mice by non-lethal irradiation and sensitized them when T cells began to repopulate. Interestingly, we found that defective Fas signaling on T cells plus antigen exposure during homeostatic proliferation was sufficient to induce prolonged eosinophilic airway inflammation. In conclusion, our data show that the combination of transient lymphopenia, abnormal Fas-signaling, and antigen exposure leads to the development of a prolonged airway eosinophilic inflammatory phase in our mouse model of experimental asthma.

Non-apoptotic Fas (CD95) Signaling on T Cells Regulates the Resolution of Th2-Mediated Inflammation.

Fas (CD95/APO-1) and its ligand (FasL/CD95L) promote the resolution of type 2 lung inflammation and eosinophilia. We previously found that Fas-deficiency on T cells, but not eosinophils, delayed resolution of inflammation. However, Fas can signal both cell death and have a positive signaling function that can actually activate cells. In this study, we investigated whether Fas-induced death or Fas-activated signaling pathways promote resolution of allergic lung inflammation. By increasing T cell survival through two Fas-independent pathways, using Bim-deficient T cells or Bcl-xL overexpressing T cells, no differences in resolution of Th2-mediated inflammation was observed. Furthermore, Th2 cells were inherently resistant to Fas-mediated apoptosis and preferentially signaled through non-apoptotic pathways following FasL treatment. Utilizing Fas-mutant mice deficient in apoptotic but sufficient for non-apoptotic Fas signaling pathways, we demonstrate that non-apoptotic Fas signaling in T cells drives resolution of Th2-mediated airway inflammation. Our findings reveal a previously unknown role for non-apoptotic Fas signaling on Th2 cells in the induction of resolution of type 2 inflammation.

Papillary fibroelastoma of the aortic valve presenting with chronic angina and acute stroke: a case report.

BACKGROUND: Papillary fibroelastomas are rare, benign cardiac tumors that are often found on cardiac valvular surfaces. Most are incidental discoveries during surgery or autopsy. The clinical presentation of fibroelastoma varies widely, ranging from clinically asymptomatic to severe thromboembolic events. CASE PRESENTATION: We report a case of 65-year-old white man diagnosed with scattered, bilateral acute cerebral hemisphere infarcts with a history of chronic angina. Transesophageal echocardiography identified a fibroelastoma on the right coronary cusp of the aortic leaflet. Cardiac catheterization revealed mild non-obstructive stenosis. We postulate that the etiology of his angina is related to the dynamic occlusion of his right coronary ostium by the fibroelastoma. CONCLUSIONS: To the best of our knowledge, this is the first case report describing a patient with a cardiac papillary fibroelastoma who presented with both chronic angina and acute stroke.

A rare case of fetal adenocarcinoma of the lung.

Fetal adenocarcinoma is a rare lung malignancy associated with improved outcomes compared to more common adenocarcinoma variants. We describe a case of a 31-year-old woman who presented with right-sided chest pain, and was subsequently diagnosed with an intermediate-grade stage IV fetal adenocarcinoma with chest wall invasion. She was treated with surgical resection and adjuvant radiation.

Fas ligand expression on T cells is sufficient to prevent prolonged airway inflammation in a murine model of asthma.

Our previous studies revealed that, in a murine model of asthma, mice that received Fas-deficient T cells developed a prolonged phase of airway inflammation, mucus production, and airway hyperreactivity that failed to resolve even 6 weeks after the last challenge. To investigate how Fas-Fas ligand (FasL) interaction occurs between T cells and other cells in vivo, Gld mice with abnormalities of the FasL signaling pathway were used. The reconstituted mice were made by transferring T cells from B6 or Gld mice to Rag(-/-) or FasL-deficient Rag(-/-) mice. We found that Rag(-/-) mice that received B6 T cells resolved the airway inflammation, whereas FasL-deficient Rag(-/-) mice that received Gld T cells developed a prolonged airway inflammation at Day 28, with decreased IFN-gamma production. Both FasL-deficient Rag(-/-) mice that received B6 T cells and Rag(-/-) mice that received Gld T cells also had completely resolved their airway inflammation by Day 28 after challenge. Interestingly, FasL-deficient Rag(-/-) mice that received Gld T cells eventually resolved airway inflammation at Day 42, with a similar level of IFN-gamma production to that of control group. These results demonstrate that FasL expression on either T cells only or non-T cells only was sufficient for the eventual resolution of airway inflammation, and the prolonged airway inflammation in FasL-deficient Rag(-/-) mice that received Gld T cells was correlated with decreased IFN-gamma production by Gld T cells.

Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma.

BACKGROUND: Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA1-3). We have demonstrated that LPA induced cytokine and lipid mediator release in human bronchial epithelial cells. Here we provide evidence for the role of LPA and LPA receptors in Th2-dominant airway inflammation. METHODS: Wild type, LPA1 heterozygous knockout mice (LPA1+/-), and LPA2 heterozygous knockout mice (LPA2+/-) were sensitized with inactivated Schistosoma mansoni eggs and local antigenic challenge with Schistosoma mansoni soluble egg Ag (SEA) in the lungs. Bronchoalveolar larvage (BAL) fluids and lung tissues were collected for analysis of inflammatory responses. Further, tracheal epithelial cells were isolated and challenged with LPA. RESULTS: BAL fluids from Schistosoma mansoni egg-sensitized and challenged wild type mice (4 days of challenge) showed increase of LPA level (approximately 2.8 fold), compared to control mice. LPA2+/- mice, but not LPA1+/- mice, exposed to Schistosoma mansoni egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA2+/- and LPA1+/- mice showed decreases in bronchial goblet cells. LPA2+/- mice, but not LPA1+/- mice showed the decreases in prostaglandin E2 (PGE2) and LPA levels in BAL fluids after SEA challenge. The PGE2 production by LPA was reduced in isolated tracheal epithelial cells from LPA2+/- mice. These results suggest that LPA and LPA receptors are involved in Schistosoma mansoni egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.

CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo.

Previous work has shown ICOS can function independently of CD28, but whether either molecule can compensate for the other in vivo is not known. Since ICOS is a potent inducer of Th2 cytokines and linked to allergy and elevated serum IgE in humans, we hypothesized that augmenting ICOS costimulation in murine allergic airway disease may overcome CD28 deficiency. While ICOS was expressed on T cells from CD28(-/-) mice, Th2-mediated airway inflammation was not induced in CD28(-/-) mice by increased ICOS costimulation. Further, we determined if augmenting CD28 costimulation could compensate for ICOS deficiency. ICOS(-/-) mice had a defect in airway eosinophilia that was not overcome by augmenting CD28 costimulation. CD28 costimulation also did not fully compensate for ICOS for antibody responses, germinal center formation or the development of follicular B helper T cells. CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo.

CD43 regulates Th2 differentiation and inflammation.

CD43 is a highly glycosylated transmembrane protein that regulates T cell activation. CD43(-/-) T cells are hyperproliferative and the cytoplasmic tail of CD43 has been found to be sufficient to reconstitute wild-type proliferation levels, suggesting an intracellular mechanism. In this study, we report that upon TCR ligation CD43(-/-) T cells demonstrated no increase in tyrosine phosphorylation but a decreased calcium flux. Interestingly, CD43(-/-) T cells preferentially differentiated into Th2 cells in vitro, and CD43(-/-) T cells show increased GATA-3 translocation into the nucleus. In vivo, CD43(-/-) mice exhibited increased inflammation in two separate models of Th2-mediated allergic airway disease. In contrast, in Th1-mediated diabetes, nonobese diabetic CD43(-/-) mice did not significantly differ from wild-type mice in disease onset or progression. Th1-induced experimental autoimmune encephalomyelitis to MOG(35-55) was also normal in the CD43(-/-) mice. Nonetheless, the CD43(-/-) mice produced more IL-5 when restimulated with MOG(35-55) in vitro and demonstrated decreased delayed-type hypersensitivity responses. Together, these data demonstrate that although CD43(-/-) T cells preferentially differentiate into Th2 cells, this response is not sufficient to protect against Th1-mediated autoimmune responses.

Signaling through Fc gamma RIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation.

Although inhibitory Fc gamma receptors have been demonstrated to promote mucosal tolerance, the role of activating Fc gamma receptors in modulating T helper type (Th)2-dependent inflammatory responses characteristic of asthma and allergies remains unclear. Here, we demonstrate that signaling via activating Fc gamma receptors in conjunction with Toll-like receptor 4 stimulation modulated cytokine production from bone marrow-derived dendritic cells (DCs) and augmented their ability to promote Th2 responses. Ligation of the low affinity receptor Fc gamma RIII was specifically required for the enhanced Th2 responses, as Fc gamma RIII(-/-) DCs failed to augment Th2-mediated airway inflammation in vivo or induce Th2 differentiation in vitro. Further, Fc gamma RIII(-/-) mice had impaired Th2 cytokine production and exhibited reduced airway inflammation, whereas no defect was found in Fc gamma RI(-/-) mice. The augmentation of Th2 immunity was regulated by interleukin 10 production from the DCs but was distinct and independent of the well-established role of Fc gamma RIII in augmenting antigen presentation. Thus, our studies reveal a novel and specific role for Fc gamma RIII signaling in the regulation of Th cell responses and suggest that in addition to immunoglobulin (Ig)E, antigen-specific IgG also contributes to the pathogenesis of Th2-mediated diseases such as asthma and allergies.