Localized Rosai-Dorfman disease: Case report of an uncommon tumor and a brief review of the literature

 Corresponding author: Mohamed Aziz. Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Localized Rosai-Dorfman disease: Case report of an uncommon tumor and a brief review of the literature Sharon Ayad 2, Mareena Ayad 4, Javier A. Alemán 6, Armando Piedra 6, Ramsharan Padhy 2, Amanda Canellas 3, Zainab Jasim 5, Jessica Jahoda 1, 2 and Mohamed Aziz 1, * 1 Research Writing and Publication (RWP), LLC, NY, USA. 2 American University of the Caribbean School of Medicine US. 3 St. George's University School of Medicine, Grenada. 4 Medical University of the Americas, Nevis, St. Kitts and Nevis. 5 UMHS University of Medicine and Health Sciences, St. Kitts. 6 Universidad Iberoamericana de Medicina (UNIBE), Santo Domingo. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 451-458 Publication history: Received on 16 July 2025; revised on 24 August 2025; accepted on 26 August 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.23.2.0776 Abstract Rosai-Dorfman Disease (RDD) is a rare histiocytic disorder that is usually marked by enormous lymphadenopathy, with or without extranodal disease. We report a diagnostically challenging case of localized RDD in a 51-year-old male who first presented to be evaluated for progressive, painless bilateral cervical lymphadenopathy and a slowly growing subcutaneous lump over the left supraclavicular region. The lack of constitutional symptoms and the slow progression of disease at the beginning contributed to the wide range of differential diagnoses, including lymphoma, soft tissue sarcoma, Erdheim-Chester disease (ECD), Rosai-Dorfman Disease (RDD), and Langerhans cell histiocytosis (LCH). Imaging studies showed bilateral cervical and supraclavicular lymphadenopathy and a well-defined mass in the left supraclavicular region with no visceral or skeletal lesions. Histologic examination of the excision tissue of a lymph node and fine-needle aspiration (FNA) of the supraclavicular mass showed classic RDD findings with large histiocytes displaying emperipolesis and a mixed inflammatory background. The immunohistochemistry (IHC) studies were positive for S100, CD68, CD163, OCT2, and cyclin D1 but negative with CD1a and BRAF V600E. A precision oncology approach was possible due to the identification of a MAP2K1 mutation by molecular profiling. After the surgical removal of the lesion in the supraclavicular region, the patient was put on the treatment course with the MEK inhibitor cobimetinib, which caused a significant reduction in lymphadenopathy. Side effects were not significant. The patient is still functional and without disease at the three-year follow-up. This case illustrates the significance of tissue diagnosis and molecular profiling of atypical lymphadenopathy and soft tissue lesions. Identification of mutations in the MAPK pathway presents an opportunity for effective treatment in RDD, reflecting the move toward precision treatment in histiocytic and many other conditions. Keywords: Rosi-Dorfman; Soft tissue; Lymph nodes; Molecular; Immunohistochemistry 1. Introduction Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis. It is caused by excessive production of distinctive histiocytes with emperipolesis by phagocytosis of viable inflammatory cells. [1] It classically occurs in World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 451-458 452 children and young adults with painless, massive cervical lymphadenopathy. However, the clinical spectrum is wide, and many patients exhibit extra nodal involvement, such as the skin, bone, and central nervous system. [2] This wide range of presenting features is what makes RDD a formidable diagnostic challenge, and it can simulate a variety of different diseases, from infectious and reactive processes to malignant neoplasms such as lymphoma and metastatic carcinoma. [3] Because RDD has ambiguous clinical and radiological features, the histopathological confirmation is mandatory for the diagnosis of RDD. However, morphology alone is not always sufficient, leading to potential diagnostic errors. IHC studies are essential, and the usual pattern of positive staining for S100, CD68, and CD163, negative for CD1a, helps distinguish RDD from other histiocytic disorders, such as Langerhans cell histiocytosis. [4] Moreover, the finding of somatic mutations of the MAPK signaling pathway (e.g., MAP2K1, NRAS, KRAS) in approximately 50 percent of RDD cases has transformed the field of RDD diagnosis and treatment. [5] The molecular studies have ceased to be just a potent diagnostic tool but have become essential in the identification of the possible targets of the therapy. It is thus important that clinicians and pathologists have a high index of suspicion and consider RDD as part of the differential diagnosis of unexplained lymphadenopathy or soft tissue masses. Modern ancillary testing is vital in the correct diagnosis of patients, which would lead to proper management. Although most cases of localized RDD are selflimiting and may be followed by symptomatic or systemic disease, which may necessitate treatment, which can involve surgery, corticosteroids, or, in mutation-positive cases, more frequently, targeted MEK inhibitors. [6] The prognosis is usually good, especially when there is no systemic or critical organ involvement. We present a case of Localized RDD and provide a brief review of the relevant literature on this uncommon condition. [7] 2. Case presentation A 51-year-old man presented to the clinic with a seven-month history of seeing two masses swell up on each side of his neck. The masses were painless, rubbery, and freely movable. Additionally, he noticed a gradually growing large soft tissue mass at the left supraclavicular region. The patient initially thought these masses were cysts or lipomas and did not worry about them. The gradual, progressive increase in size of these lesions, discomfort, and, for cosmetic reasons, he decided to visit the clinic and seek medical attention. He did not report fever, night sweats, or weight loss. He was a healthy man, active and vivacious, with no significant medical history, and his family was also healthy. Physical examination revealed large neck nodules, consistent with enlarged lymph nodes, the largest measuring 2-3 cm in greatest dimension. In addition, a large soft tissue 5-6 cm mass was noted at the supraclavicular region; the features did not match the patient’s expectation of cysts or lipomas. This complex of signs and symptoms, including lymph node swelling and a single soft tissue mass, raised significant concerns. The initial clinical differential diagnosis was very broad, encompassing serious potential causes of the condition, such as lymphoma and metastatic cancer, along with less common conditions, such as Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), and Langerhans cell histiocytosis (LCH). A battery of tests was the start of the diagnostic process. Blood tests showed evidence of chronic inflammation, with mild anemia, and increased inflammatory markers such as ESR and CRP. A serum protein electrophoresis was suggestive of a polyclonal hypergammaglobulinemia, a nonspecific finding of immune activation. However, importantly, no monoclonal spike was present, which would have suggested a plasma cell malignancy. Imaging studies added more details: a CT and MRI showed that the lymphadenopathy was localized to the neck and not the chest, abdomen, or pelvis, consistent with a localized nodal disease with subcutaneous tissue involvement. The clavicular mass did not indicate aggressive invasion or the involvement of the bones. It was contained, which was not in support of the possibility of such diseases as Erdheim-Chester disease. After a debate regarding the tissue sampling site, it was decided to perform a tissue biopsy of one of the lymph node neck masses, in addition to a fine needle aspiration (FNA) of the clavicular mass. Expert cytopathology was available, and the FNA was performed to ensure that the two sites represent the same process, and to provide more tissue sampling for various studies. The actual progress was achieved with the histopathology findings and the IHC profile. Histologic analysis from both sites demonstrated similar findings, consistent with a single disease entity. Examination revealed markedly distended lymph node sinuses and dermal infiltration by large histiocytes with abundant eosinophilic cytoplasm and prominent emperipolesis, engulfment of intact lymphocytes and other inflammatory cells. These lesional histiocytes were embedded within a background of fibrosis and mixed inflammatory infiltrates, including plasma cells, lymphocytes, and occasional neutrophils. Mild nuclear atypia was observed in the histiocytes. (Figure 1 A, B, C) The cytologic features were more subtle in the FNA specimen compared to the lymph node biopsy, but remained morphologically concordant. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 451-458 453 IHC studies showed that the histiocytes were strongly positive for CD68 and CD163, with co-expression of S100 protein, OCT2, and cyclin D1. The lesional cells were negative for CD1a. The IH profile was critical in narrowing the differential diagnosis: CD1a negativity helped exclude LCH, while the combination of CD68/CD163 and S100 positivity was highly characteristic of RDD. The polytypic nature of plasma cells was confirmed by kappa and lambda light chain studies, ruling out clonal plasma cell neoplasms. BRAF V600E immunohistochemistry was negative, further differentiating RDD from histiocytic disorders driven by BRAF mutations. Based on the histopathologic and IHC findings, a diagnosis of localized Rosai-Dorfman disease was established, involving bilateral cervical lymph nodes and a solitary extranodal skin/soft tissue lesion of the left supraclavicular region. For the diagnostic and therapeutic value of potential targetable mutations, molecular testing was performed. Nextgeneration sequencing revealed a MAP2K1 gain-of-function mutation, a finding that not only confirmed the diagnosis but also introduced the possibility of targeted therapy using MEK inhibitors. There was a tumor board discussion of the case, and some expressed their opinion on surgically removing the clavicular mass (Debulking) due to the large size, patient's discomfort, and cosmetic considerations. The patient was counseled on all data, and all details were explained to him; he decided to undergo surgical excision. The patient underwent surgical removal of the large clavicular mass largely due to cosmetic reasons. Postoperatively, he was placed on a MEK inhibitor, cobimetinib, since he had the MAP2K1 mutation. The response was impressive. Within a month after treatment, his cervical lymph nodes began to swell. Three years on, the patient was still in remission and had a complete recovery, with no lymph nodes and no clavicular mass. Figure 1 Histomorphology of Rosai-Dorfman Disease (RDD), Lymph node biopsy • 1A: Low-power view showing markedly distended lymph node sinus and infiltration by large histiocytes (HandE stain X20) • 1B: Intermediate power view showing mixed inflammatory cells and histiocytes (HandE stain X40) • 1C: High power view showing engulfment of intact lymphocytes and other inflammatory cells by large histiocytic cells (Blue arrow) (emperipolesis) (HandE stain X60) 3. Discussion 3.1. History and WHO classification Rosai-Dorfman disease (RDD) is named after the two pathologists, Juan Rosai and Ronald Dorfman, who initially identified it in 1969, and initially referred to it as sinus histiocytosis with massive lymphadenopathy. Although such cases had already been documented in the past, their work was the first to define RDD and separate it clearly concerning other disorders, such as lymphoma. [8] In 1972, Dr. Rosai and Dr. Dorfman expanded on their earlier work, publishing a paper describing thirty-four cases, which played a critical role in establishing a clinical picture for the disease. [9] It was a commitment for both Dr. Rosai and Dr. Dorfman to continue conducting studies on the disease, and their dedication to research led them to set up databases where physicians can input their cases and all associated findings. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 451-458 454 In 1976, Dr. Diebold released a study in which he referred to the disease for the first time as Rosai-Dorfman disease. [10] It was long believed that RDD is a non-cancerous disorder with an unknown response to an infection or an immune system problem. [11] But with the finding of gene mutation in the MAPK signaling pathway in many patients, our knowledge on the disease has increased significantly, and now it is recognized that RDD is classified as a rare histiocytic neoplasm. [5] RDD is an uncommon illness, and it is estimated that approximately 100 new cases are noted annually in the United States. It may occur in individuals of any age, although it is the most prevalent among two categories of individuals, children under 10 and adults aged between 40 and 60. [11] The disease is more prevalent in men and is found all over the world, but some studies indicate it might be more prevalent in individuals of African descent. [6] The cause of RDD is not yet fully understood, and there are no definite environmental or genetic risk factors identified. The association between RDD and autoimmune disorders or previous infections, such as human herpesvirus 6 (HHV-6), indicates that an immune system response may be a factor in some instances. [12] The identification of the genetic nature of the disease has altered its classification. The 2016 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues added RDD to the group of histiocytosis and dendritic cell neoplasms. More recently, RDD has also been grouped in the 2022 International Consensus Classification as well as the 5th edition of the WHO Classification in the "histiocytic/dendritic cell neoplasms" category. [13] The development of this change was influenced by the fact that mutations of the soma (such as MAP2K1, NRAS, and KRAS) were found in nearly half of all RDD cases. [2] This observation made RDD a clonal disease and has opened the way to new targeted therapies. 3.2. Clinical Presentation and Imaging Findings Rosai-Dorfman Disease (RDD) generally presents with vague symptoms, which makes it difficult to diagnose correctly in its early stages. Individuals are typically affected during childhood and early adulthood, most commonly within the second and third decades of life. There are various forms in which RDD can arise, including involvement of the lymph nodes (classical), extranodal, and cutaneous sites. [4] The classical form of RDD causes painless swelling of lymph nodes with concomitant fever, unintentional weight loss, and night sweats [6] Although the cervical lymph nodes are the most common site for the disease to arise, other regions, including the inguinal, retroperitoneal, and mediastinal lymph nodes, are other possible sites. Upon physical examination, the involved lymph nodes may be observed as enlarged and matted, resulting in firm multinodular masses. RDD can also extend into extranodal locations in approximately 40% of cases, most commonly within the skin and central nervous system, but can also involve the nasal cavity, bone, and orbital tissue. [15] Another form of RRD, the cutaneous presentation known as cutaneous Rosai-Dorfman disease (CRDD), is often seen in an older demographic and female-predominant, presenting as multiple red-brown papules or nodules. [15] [16] Although RDD has nonspecific imaging findings, radiology can help screen for the extent of disease involvement as well as monitor for disease recurrence. Upon initial presentation of enlarged lymph nodes, an ultrasound may be performed, which would demonstrate enlarged hypoechoic lymph nodes. Similarly, CT scans with contrast may display enlarged solid lymphadenopathy with surrounding fat stranding. [17] Staging is determined using CT scans of the neck, chest, abdomen, and pelvis to look for sites of distant disease. If RDD is suspicious for CNS involvement, then a brain MRI should be performed to rule out other causes of the lesion, such as being misdiagnosed as a meningioma or other neoplasms. Both CT and MRI usually display the common finding of homogenous enhancement of the diseased lymph nodes. [18] Although radiologic imaging may aid in the diagnosis of RDD, a combination of physical examination, imaging, and histopathology is crucial for a definitive diagnosis. 3.3. Pathology diagnosis and ancillary studies Rosai-Dorfman disease (RDD) is diagnosed definitively by histopathological examination of affected tissue, and as such, adequate biopsy is a necessary part of the diagnostic process. Although fine-needle aspiration (FNA) may be suggestive, an excisional biopsy of a lymph node or core biopsy of an extranodal mass may be preferred to obtain adequate tissue to evaluate architecture and perform a comprehensive ancillary study panel. [19] Microscopically, the most characteristic feature of RDD is the dramatic appearance of sinus histiocytosis, with the sinus of the lymph node being massively dilated and occupied by a large population of large histiocytes that have a characteristic appearance. [4] They have a plentiful amount of pale to eosinophilic cytoplasm with round-to-oval nuclei containing fine chromatin and small nucleoli. [4] Not always seen, but pathognomonic is emperipolesis: the engulfment of intact, viable inflammatory cells, usually lymphocytes, but also plasma cells and neutrophils, within the cytoplasm of World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 451-458 455 these large histiocytes. [15] A dense mixed inflammatory infiltrate, composed mostly of plasma cells and lymphocytes, and commonly accompanied by fibrosis, is typical of the background. The infiltrate is similar in extranodal sites, the normal tissue architecture being replaced by sheets of these typical histiocytes. [15] [4] Despite these typical characteristics, the differential diagnosis may be wide. It encompasses other histiocytic diseases, including Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD), and malignancies, including melanoma, lymphoma (especially lymphoplasmacytic or Hodgkin lymphoma), and metastatic carcinoma. [3] It is here that immunohistochemistry (IHC) can be invaluable. RDD histiocytes are invariably positive with the pan-histiocytic CD68 and CD163, and more importantly, they also express S100 protein. They are negative in characteristic ways to CD1a and Langerin (CD207), effectively eliminating LCH. BRAF V600E stain negativity may be used to distinguish RDD from a group of ECD and LCH patients. The stains to exclude metastatic carcinoma and melanoma (staining negative to cytokeratins (AE1/AE3) and melanoma markers (SOX10 or Melan-A) will be negative. [16] [17] In the contemporary world, molecular testing has provided an extra dimension of diagnostic accuracy and therapeutic significance. Somatic mutations in MAPK/ERK pathway genes are found in about half of RDD cases, most frequently in NRAS, KRAS, and ARAF, and, as in our case, MAP2K1. [5] [14] The detection of these mutations not only proves the diagnosis of a clonal, neoplastic process but also paves the way to targeted therapy with MEK inhibitors, which have been very effective in patients with refractory or systemic disease. 3.4. Treatment strategies and outcomes Rosai-Dorfman Disease is a rare histiocytic disorder involving extensive lymphadenopathy, which most generally warrants surgical excision. This intervention is recommended for patients with symptomatic reports leading to functional impairment. The most common site of excision in patients with this disease is subcutaneous nodular involvement, with an average response time to surgery of 12 months. [14] [15] Surgical resection may improve overall quality of life by alleviating upper airway obstruction due to extranodal compression. [19] Corticosteroids, most notably Prednisone, are used as the first-line treatment in patients, with a 56% response rate in cases. [14] Prednisone is beneficial in reducing inflammation caused by an increased lymph node size. The general treatment method entails observation and slow tapering of the corticosteroid. Although response to steroids is variable, metastasis to distant tissue, such as the trachea and the kidneys, fails to respond to this method of treatment. [19] The discovery of mutations in the MAPK signaling pathway has established a landmark in the treatment of RDD. Genetic mutation of major regulators, including BRAF, NRAS, and MAP2K1, has led to the possibility of precision medicine approaches that were not previously possible among such patients. [5] [14] The most promising therapeutic interventions include BRAF inhibitors, e.g., dabrafenib, and MEK inhibitors, e.g., trametinib and cobimetinib (was used for treatment of our case). These agents have shown the capacity to produce quick and lasting clinical responses even among patients who have not responded to conventional therapies. [20] Their effectiveness highlights a paradigm change in the treatment of RDD, especially the refractory cases and those that involve vital organs. Radiation therapy, although presenting with a low response rate in this disease, is reserved for cases that do not respond to surgery, corticosteroids, or other treatments. [21] The prognosis for Rosai-Dorfman Disease is variable based on the stage at diagnosis and the extent of organ involvement. However, there is a favorable prognosis as the risk of mortality is low. Prognosis also continues to improve, especially in patients presenting with extra nodal involvement and targeted treatment therapy. The duration of treatment is not yet established; however, an average of six to twelve months, followed by observation of treatment response, is generally recommended. [14] RDD has a good prognosis in general. A large proportion of patients have a benign, indolent disease course, and survival is high in the long term. [22] This encouraging prognosis is also backed by the fact that the disease, in many instances, is self-limiting. Although most patients experience spontaneous regression of this self-limiting condition and solely require observation, progression of this disease to organs such as the kidneys may pose severe complications and warrant a more aggressive treatment protocol. [7] 3.5. Pathogenesis and Pathophysiology Rosai-Dorfman disease (RDD) pathogenesis was controversial since its inception and has gone through various phases, beginning as a theory of a reactive, immune-mediated process, and is now classified as a clonal neoplasm. The characteristic strong inflammatory infiltrate and relation to autoimmune diseases historically prompted the hypothesis that RDD was an abnormal immune response to an unknown antigen, of potentially infectious origin, including Human World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 451-458 456 Herpesvirus-6 (HHV-6). [6] Although this may still play a role in some instances, the identification of somatic mutations has fundamentally changed our thinking to a model of oncogene-driven disease. [5] Dysregulated activation of the mitogen-activated protein kinase (MAPK) signaling pathway is the key pathophysiological mechanism in a significant proportion of RDD cases. [1] It is an important cellular cascade pathway that controls cell proliferation, differentiation, and survival. Mutations in the genes that play a central role in this pathway, such as NRAS, KRAS, ARAF, and MAP2K1, are present in approximately half of RDD patients. [5] These mutations are normally gain-of-function, resulting in unregulated, constitutive activation of the pathway. This continued signaling enhances the proliferation and survival of histiocytes, leading to their accumulation in the lymph nodes and extranodal sites. [1] [5] The mutation in MAP2K1, which was found in our patient, is a direct activator of MEK, a downstream element of the pathway, so there is an obvious molecular driver of the condition. [4] The morphological peculiarities of RDD, such as the phenomenon of emperipolesis, are also associated with this distorted signal. [1] The mutated histiocytes seem to establish a particular cytokine and chemokine microenvironment that attracts and then engulfs other inflammatory cells. Although the mechanism of emperipolesis is uncertain, it is believed to be caused by an aberrant cell-cell adhesion and signaling mechanisms that are directed by the neoplastic histiocytes. [4] Thus, RDD is currently most appropriately conceptualized as a clonal histiocytic neoplasm in which oncogenic mutations within the MAPK pathway promote histiocytic proliferation and generate a distinct, inflammationrich tumor microenvironment. [5] 3.6. What did we learn from this case? This report describes a case of a 51-year-old male patient with localized RDD that had bilateral cervical lymphadenopathy and a large single extranodal soft tissue mass in the supraclavicular region. This presentation is congruent with the established clinical spectrum of RDD, which, although traditionally linked with massive lymphadenopathy in young individuals, is by no means restricted to middle-aged adults and often includes extranodal sites, with the skin and soft tissue being the most common. The patient also has no systemic B symptoms (fever, night sweats, weight loss), and localized disease is also more characteristic and often has a more indolent course. The diagnostic process, in the presented case, points to the necessary presence of a modern and advanced pathological assessment. The first general differential diagnosis, such as lymphoma and metastatic cancer, is natural due to the clinical appearance. The histopathology was used to make a definitive diagnosis showing the characteristic features of RDD, i.e., sheets of large histiocytes with striking emperipolesis. The immunohistochemical profile is essential for arriving at the correct diagnosis: intense S100, CD68, and CD163 positivity with decisive negativity of CD1a, which ruled out Langerhans cell histiocytosis. The classic IHC pattern helped in the diagnosis. An especially interesting finding in the case was a MAP2K1 gain-of-function mutation identified using next-generation sequencing. The finding is of utmost significance in several ways. It first establishes that the disease is neoplastic in the patient, which is consistent with the current knowledge of RDD as a clonal disease that is caused by the activation of the MAPK pathway. Second, and more importantly, clinically, it furnished a direct therapeutic target. This molecular finding led to the decision to treat this patient with the MEK inhibitor cobimetinib, after surgical debulking of the large symptomatic mass. The remarkable and long-lasting remission of the patient offers the practical example of the immense role of precision medicine in the treatment of histiocytic disorders. This result is highly suggestive of the increasing agreement that molecular testing ought to be regarded as a routine component of the diagnostic evaluation of RDD, not merely to confirm the diagnosis, but also to inform a personalized treatment approach, particularly when the patient needs systemic therapy. 4. Conclusion In this report, the pathologic process highlighted the essentiality of histopathology and immunohistochemistry in distinguishing RDD and its clinical and pathological mimics. The most important feature of this case is the discovery of a somatic MAP2K1 gain-of-function mutation, which solidly locates the disease in the continuum of MAPK-driven neoplasms. This was not just an academic discovery that was of interest to a few; it informed a therapeutic intervention that was successful and effective. The deep and sustained remission of the patient after treatment with the MEK inhibitor cobimetinib is a strong, real-life evidence of the effectiveness of precision medicine. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 451-458 457 Overall, this case demonstrates why clinicians and pathologists should include RDD in the differential diagnosis of lymphadenopathy and masses of the soft tissues in adults. Besides, it emphasizes the increased role of molecular testing in the routine histiocytic disease diagnostic workup. Such actions can offer diagnostic certainty, prognostic data, and, most importantly, a route to highly effective treatment which can make a significant improvement in patient outcomes. Compliance with ethical standards Acknowledgments Special thanks to MD candidates Laraib Humayun, Gabriella Piedra, and Arline Ficarra for their assistance in reviewing the final manuscript. In addition, we appreciate the assistance of Grammarly's language editor, which helped improve the manuscript by identifying and correcting errors in grammar, spelling, punctuation, and style. Disclosure of conflict of interest All authors make the following declarations • Payment/services information: All authors have declared that they received no financial support from any organization for the submitted work. • Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might be interested in the submitted work. Statement of ethical approval Ethical review and approval were not required for this study involving human participants. The paper has been sufficiently anonymized to maintain the patient's confidentiality. Statement of informed consent The patient was lost to follow-up, and all attempts to reach the family members were unsuccessful. Therefore, the paper has been sufficiently anonymized to maintain patient confidentiality. Data access statement All relevant data are included in the paper. 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