An extremely rare case of Rosai-Dorfman-Destombes disease in the spleen with secondary thrombocytopenia: a case report

Introduction

Rosai-Dorfman-Destombes disease (RDD), also called sinus histiocytosis with massive lymphadenopathy, was thoroughly studied and officially named by Rosai and Dorfman in 1969 (1). RDD is typically a rare, benign condition characterized by proliferation of histiocytes. Its clinical manifestations are diverse, including painless lymphadenopathy or extra-nodal soft tissue masses, fever, weight loss, and so on (2). Depending on the extent of involvement, RDD can be classified as nodal, extra-nodal, or mixed-type (3). It primarily affects bilateral cervical lymph nodes, presenting as large, painless masses. RDD without lymph node involvement accounts for less than 20%. The extra-nodal form resembles solid tumors, mainly affecting the bones, nerves, nasal cavity, and breasts. Clinical manifestations are highly variable, necessitating identification and differential diagnosis based on the characteristics of the affected site and additional investigations.

We report here a case of RDD originating from the spleen with secondary thrombocytopenia treated at the Hepatobiliary and Pancreatic Surgery Department of the Second Hospital of Jilin University. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-207/rc).

Case presentation

A 68-year-old female patient was presented with abdominal discomfort for over 2 months. An operation was performed on a benign pseudotumor in the right lower lung forty years ago, and an operation was conducted on a benign tumor in the right breast thirty years ago. Rheumatoid arthritis was diagnosed and treated orally with tofacitinib around ten years ago. Hemorrhoids were surgically removed 6 years ago. The patient had a 10-year history of diabetes and was treated with insulin injections. The patient had no familial history of similar diseases or drug or food allergies. Physical examination revealed no palpable cervical lymph nodes. Abdominal examination had no significant findings. Positron emission tomography-computed tomography (PET-CT) scan showed an irregularly shaped and locally protruding spleen with nodules and mass shadows of comparable or marginally reduced density, with indistinct margins and radioactive uptake akin to that of the adjacent normal splenic tissue. The findings suggest a benign condition, but the possibility of splenic hemangioma/lymphangioma cannot be ruled out (Figure 1). The admission blood tests revealed a platelet count of 39×10⁹ cells/L, while all other parameters were within acceptable limits; HIV and hepatitis B antibodies tested negative. The patient exhibited signs of thrombocytopenia.

Figure 1 PET-CT: multiple lesions in the spleen, with metabolism similar to the surrounding splenic tissue, considered benign, not excluding the possibility of splenic hemangioma/lymphangioma. (A) Multiple lesions observed in the spleen on coronal, sagittal, and axial planes. (B) Gross appearance. (C) Comparison of CT and PET-CT in consecutive scans. PET-CT, positron emission tomography-computed tomography.

Following consultation with a multidisciplinary team, the preliminary diagnosis suggested a benign splenic tumor. The treatment plan was explained, and informed consent was obtained from the patient and their family. Consequently, a laparoscopic splenectomy was performed in April 2024, and the surgery was successful. Postoperative pathology (Figure 2), immunohistochemical staining, and morphological features of spleen supported RDD. Microscopic examination revealed a nodular lesion characterized by numerous RDD histiocytes, which were sizable, possessed large vacuolated nuclei, exhibited copious eosinophilic or foamy cytoplasm, and displayed pseudopodia-like extensions. Additionally, numerous lymphocytes, plasma cells, and neutrophils were infiltrating the area, with no significant fibrous tissue hyperplasia observed. Immunohistochemical staining results were: <first time>: CK(AE1/AE3)(–), TTF-1(–), CD68(+), CD31(–), CD34(–), CD8(–), CD21(–), SMA(–), EBER(–), Ki67 (positivity rate 10%); <second time>: BRAFV600E mutation-specific antibody (VE1) (Ventana immunohistochemical enhanced amplification kit) (–), S-100(+), CyclinD1(+), CD1a (plasma +), CD207(–), Oct2(+), ALK(–), ERG(–).

Figure 2 Pathology report. (A) Splenomegaly: splenectomy was performed, the spleen size was 12×10×5 cm³, and two grey-red nodular masses were observed, with diameters 2 and 5 cm respectively. (B) Cross-section of grey-red and soft-textured spleen, with ill-defined borders. (C) HE staining, 40×: under the microscope, the lesion appeared nodular with many RDD histiocytes, which are large, with big vacuolated nuclei, abundant eosinophilic or foamy cytoplasm, and showed pseudopodia-like extensions. (D) HE staining, 200×: numerous lymphocytes, plasma cells, and neutrophils infiltrated the area, and no significant fibrous tissue hyperplasia was observed. HE, hematoxylin and eosin; RDD, Rosai-Dorfman-Destombes disease.

The patient was regularly followed up after surgery. Anticoagulants were used postoperatively to reduce the elevated platelet state following splenectomy. The platelet level recovered to 222×10⁹ cells/L 1-month post-operation, confirming the cause of thrombocytopenia secondary to splenic RDD, thereby discontinuing anticoagulants. An abdominal CT scan performed 5 months post-operation showed no significant abnormalities. The patient’s overall condition was satisfactory, with no notable symptoms or indicators detected.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Primary RDD of the spleen is extremely rare, with only four relevant case reports identified in both Chinese and English literature databases (Table 1). The disease’s characteristics and systemic manifestations vary greatly, necessitating more cases for systematic analysis.

RDD is a rare histiocytic disease with an unclear mechanism that is prone to misdiagnosis. The classical features of RDD include bilateral painless lymphadenopathy, often accompanied by symptoms such as fever, weight loss, and anemia. Based on the location of the lesions, RDD can be classified into three types: nodal (the most common), extra-nodal, and mixed (3). In the extra-nodal subtype, RDD’s manifestation in the abdominal viscera is extremely rare (8).

Numerous instances of RDD indicate that its etiology may be influenced by harboring mutations in the MAPK pathway, including MAP2K1, KRAS, and NRAS (9). Some researchers believe that RDD is associated with viral infections, such as human herpesvirus, human parvovirus B19, and Epstein-Barr virus (10,11). Earlier studies suggested that the pathogenesis of RDD might be related to the monocyte/macrophage colony-stimulating factor (3). RDD is a clonal myeloid disorder associated with immune dysregulation (including immune cytopenia and lupus) in about 30% of cases. In the case presented here, the patient’s history of rheumatoid arthritis partly supports this perspective.

Early diagnosis of RDD remains challenging. The PET-CT findings of this patient were compared with various benign splenic tumors, such as splenic hemangioma and splenic lymphoma, lacking specific manifestations (12). However, a recent case report described the diagnostic challenges associated with RDD, particularly in the extra-nodal type. Polyclonal hypergammaglobulinemia and Fluorodeoxyglucose-avid bone lesions on PET-CT may occasionally provide diagnostic indications.

Accurate diagnosis of RDD still relies on its pathological features, such as emperipolesis and storiform structure. However, emperipolesis is not specific. Therefore, more tests, including immunohistochemistry and special staining, are needed to rule out other possibilities (13).

Literature indicates that 20% of patients with RDD can recover spontaneously, 70% have stable disease, and only 10% develop localized lesions or systemic disease (14). It is crucial to remain alert since RDD might be lethal for a limited percentage of patients if the lesion compresses key organs, accompanied by mass formation and cellular infiltration, resulting in organ dysfunction (15,16).

Conclusions

The analysis of this case and other literature indicates that RDD with predominant splenic involvement exhibits diverse clinical symptoms and impacts a broad spectrum of patient demographics. This case demonstrates that in patients with multiple splenic space-occupying lesions and thrombocytopenia, particularly those with a history of rheumatoid arthritis, the potential for this disease should be contemplated, even in the absence of conventional RDD lymph node symptoms.

Based on this case and previous similar cases, the treatment plan for such patients has consistently involved surgical resection (Table 1). Further research is necessary to determine a better solution.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-207/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-207/prf

Funding: This research was funded by the Health Special Foundation of Jilin Province of China (No. 2020sczt029).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-207/coif). All authors report that this research was funded by the Health Special Foundation of Jilin Province of China (No. 2020sczt029). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Jayaram A, Al Maslamani NJ, Rahiman NAPA, et al. Rosai-Dorfman disease with paravertebral and epidural thoracic spine involvement: A case report and literature review. Radiol Case Rep 2020;15:484-8. [Crossref] [PubMed]
2. Gupta A, Arora P, Batrani M, et al. Multifocal cutaneous Rosai-Dorfman disease masquerading as lupus vulgaris in a child. An Bras Dermatol 2018;93:766-8. [Crossref] [PubMed]
3. Abla O, Jacobsen E, Picarsic J, et al. Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease. Blood 2018;131:2877-90. [Crossref] [PubMed]
4. Yang X, Fang C, Sha Y, et al. An extremely rare case of Rosai-Dorfman disease in the spleen. BMC Surg 2021;21:24. [Crossref] [PubMed]
5. Ryu H, Hwang JY, Kim YW, et al. Rosai-Dorfman disease in the spleen of a pediatric patient: A case report. World J Clin Cases 2021;9:6032-40. [Crossref] [PubMed]
6. Knox SK, Kurtin PJ, Steensma DP. Isolated splenic sinus histiocytosis (Rosai-Dorfman disease) in association with myelodysplastic syndrome. J Clin Oncol 2006;24:4027-8. [Crossref] [PubMed]
7. Ha H, Kim KH, Ahn YJ, et al. A rare case of Rosai-Dorfman disease without lymphadenopathy. Korean J Intern Med 2016;31:802-4. [Crossref] [PubMed]
8. Karajgikar J, Grimaldi G, Friedman B, et al. Abdominal and pelvic manifestations of Rosai-Dorfman disease: a review of four cases. Clin Imaging 2016;40:1291-5. [Crossref] [PubMed]
9. Leung E, Pryma C, Murphy S, et al. Rosai-Dorfman-Destombes disease in adults: a single center experience. Ann Hematol 2024;103:4467-76. [Crossref] [PubMed]
10. Dalia S, Sagatys E, Sokol L, et al. Rosai-Dorfman disease: tumor biology, clinical features, pathology, and treatment. Cancer Control 2014;21:322-7. [Crossref] [PubMed]
11. Zhao M, Li C, Zheng J, et al. Extranodal Rosai-Dorfman disease involving appendix and mesenteric nodes with a protracted course: report of a rare case lacking relationship to IgG4-related disease and review of the literature. Int J Clin Exp Pathol 2013;6:2569-77. [PubMed]
12. Kim N, Auerbach A, Manning MA. Algorithmic Approach to the Splenic Lesion Based on Radiologic-Pathologic Correlation. Radiographics 2022;42:683-701. [Crossref] [PubMed]
13. Ravindran A, Rech KL, How I. Diagnose Rosai-Dorfman Disease. Am J Clin Pathol 2023;160:1-10. [Crossref] [PubMed]
14. Duval M, Nguyen VH, Daniel SJ. Rosai-Dorfman disease: an uncommon cause of massive cervical adenopathy in a two-year-old female. Otolaryngol Head Neck Surg 2009;140:274-5. [Crossref] [PubMed]
15. Hashimoto K, Kariya S, Onoda T, et al. Rosai-Dorfman disease with extranodal involvement. Laryngoscope 2014;124:701-4. [Crossref] [PubMed]
16. Bulyashki D, Brady Z, Arif S, et al. A fatal case of Rosai-Dorfman disease. Clin Case Rep 2017;5:1407-8. [Crossref] [PubMed]