Sí, la dexametasona funciona en la enfermedad de Rosai-Dorfman (RDD), y de hecho es uno de los corticoides más utilizados en la práctica clínica para esta patología, especialmente en formas agresivas o cuando se necesita un efecto rápido e intenso.

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¿Por qué funciona?

La RDD es una histiocitosis con un componente inflamatorio autoinmune importante. La dexametasona, como corticoide potente, actúa sobre múltiples vías:

– Supresión de la proliferación histiocitaria: reduce la activación y acumulación de los histiocitos S100+.
– Antiinflamatorio potente: disminuye la citocina IL-1, el TNF-α y otros mediadores que alimentan la masa tumoral.
– Reducción del edema asociado: útil cuando la lesión comprime estructuras vecinas (como en el corazón o el SNC).

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Cuándo se prefiere dexametasona sobre prednisona/prednisolona

Escenario Razón de usar dexametasona
Enfermedad aguda severa Mayor potencia (7.5× más que la prednisona) y efecto más rápido.
Compromiso de SNC Mejor penetración en el sistema nervioso central; primera opción en masas hipofisarias con diabetes insípida.
Afectación cardíaca obstructiva Pulsos de alta dosis pueden reducir rápidamente el tamaño de la masa y estabilizar al paciente antes de cirugía o como puente a rituximab.
Edema perilesional significativo Reduce el edema vascular rápidamente (útil en masas orbitarias o vertebrales).
Preoperatorio Dosis única o pulsos previos a resección quirúrgica para reducir tamaño y sangrado.
Refractariedad a prednisona Algunos pacientes que no responden a prednisona oral pueden responder a pulsos de dexametasona.

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Esquemas de uso reportados

– Pulsos de alta dosis: 20–40 mg/día por vía intravenosa durante 3–5 días, seguido de descenso progresivo.
– Oral en dosis equivalentes: 4–6 mg cada 6 horas en fases agudas, luego tapering gradual.
– Intralesional: Inyección directa en lesiones cutáneas o de senos paranasales pequeñas (menos común que con triamcinolona, pero factible).
– Coadyuvante: Combinada con rituximab o quimioterapia para potenciar la respuesta.

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Limitaciones importantes

– No es curativa: Al igual que otros corticoides, controla la enfermedad pero no la elimina. Las recaídas son frecuentes al reducir la dosis.
– Resistencia: Aproximadamente un tercio de los pacientes con enfermedad progresiva no responde adecuadamente a corticoides solos.
– Toxicidad: Uso prolongado o en pulsos repetidos conlleva riesgo de inmunosupresión, hiperglucemia, osteoporosis, miopatía y alteraciones psiquiátricas.
– Rebound inflamatorio: La suspensión brusca puede desencadenar recaídas severas.

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Conclusión práctica

La dexametasona es una herramienta válida y frecuentemente empleada en RDD, especialmente cuando se necesita:
1. Control rápido de masa obstructiva (cardíaca, hipofisaria, traqueal).
2. Puente hacia tratamiento definitivo (cirugía o terapia dirigida).
3. Manejo de recaídas agudas en pacientes ya diagnosticados.

Sin embargo, en la RDD crónica o multisistémica, la tendencia actual es combinar corticoides (dexametasona o prednisona) con terapias de segunda línea como rituximab o inhibidores de MEK (ej. cobimetinib), para evitar la dependencia prolongada a esteroides y sus efectos adversos.

Si estás considerando dexametasona para un caso específico, la clave está en la dosis, la duración y el plan de salida (tapering), preferiblemente dentro de un protocolo que incluya control por imágenes seriadas.

La enfermedad de Rosai-Dorfman (RDD) no tiene un protocolo único de cura. El tratamiento depende de la extensión (ganglionar vs. extranodal), la severidad de los síntomas, la afectación de órganos vitales y, cada vez más, del perfil genético de la lesión. A continuación, te presento las opciones terapéuticas organizadas por nivel de evidencia y uso clínico.

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1. Filosofía general: no todo se trata
– Observación activa (watchful waiting): Muchos casos, especialmente la forma clásica con linfadenopatía masiva, son autolimitados y se resuelven en meses o años sin intervención.
– Biopsia diagnóstica + seguimiento: Si no hay compromiso de órganos vitales, el tratamiento puede ser innecesario.

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2. Tratamientos farmacológicos sistémicos

A. Corticoides (primera línea)
– Prednisona/prednisolona o metilprednisolona en pulsos.
– Son el pilar inicial en enfermedad sintomática, pero no todos los pacientes responden y las recaídas son frecuentes al suspenderlos.

B. Quimioterapia convencional (enfermedad progresiva o refractaria)
– Metotrexato (oral o subcutáneo)
– Vinblastina (especialmente en pediatría)
– Cladribina (2-CdA) o citarabina (cytarabine)
– 6-mercaptopurina
– Se reservan para enfermedad multisistémica, recidivante o que amenaza la función de órganos.

C. Terapia dirigida e inmunoterapia (nueva era)
Estas opciones han cambiado el pronóstico de la RDD refractaria:

Fármaco Mecanismo / Indicación Contexto
Rituximab Anti-CD20. Útil en enfermedad sistémica y, específicamente, ha logrado reducir masas cardíacas obstructivas. Casos refractarios; se usa off-label.
Cobimetinib Inhibidor de MEK1/2. Aprobado por la FDA para histiocitosis (incluida RDD) con mutaciones en la vía MAPK (KRAS, NRAS, MAP2K1). Primera opción terapia dirigida en RDD con mutación MAPK confirmada; estabiliza enfermedad cardíaca no resecable.
Vemurafenib / Dabrafenib Inhibidores de BRAF. Efectivos si hay mutación BRAF V600E (poco frecuente en RDD, pero comprobable).
Trametinib Otro inhibidor de MEK. Alternativa a cobimetinib en algunos protocolos.
Sirolimus (rapamycin) Inhibidor de mTOR. Casos refractarios; respuesta variable.
Imatinib Inhibidor de tirosina cinasa. Reportado en casos aislados refractarios.
Anakinra Antagonista del receptor de IL-1. Útil en enfermedad autoinflamatoria sistémica asociada.
Tocilizumab Anti-IL-6. En casos con hipergammaglobulinemia sintomática o respuesta inflamatoria exuberante.
Interferón alfa Inmunomodulador. Usado en histiocitosis refractarias antes de la era de los inhibidores de MEK.
Inmunoglobulinas IV (IVIG) Modulación inmune. Reportado en formas con compromiso inmunológico asociado.

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3. Tratamientos locales

Cirugía
– Resección completa: Es la opción con mayor probabilidad de «cura» en enfermedad localizada (ej. masa cardíaca intracardíaca bien delimitada, lesiones óseas únicas, tumoraciones cutáneas).
– Debulking (reducción de masa): Cuando la resección total es riesgosa pero hay compromiso obstructivo.

Radioterapia
– Útil para lesiones focales no resecables o como coadyuvante post-cirugía con márgenes positivos.
– Dosis bajas a moderadas (20–36 Gy) suelen ser suficientes.

Corticoides intralesionales
– Inyección local en lesiones cutáneas o de senos paranasales pequeñas.

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4. Manejo específico de la afectación cardíaca

Dado el contexto de nuestra conversación previa, el abordaje de la RDD cardíaca es multimodal:

1. Resección quirúrgica: Tratamiento de elección si la masa es accesible y el paciente tolera el procedimiento. Ofrece la mejor chance de remisión completa.
2. Rituximab: Ha demostrado reducir masas auriculares derechas grandes, evitando cirugía de alto riesgo.
3. Inhibidores de MEK (cobimetinib): Opción para enfermedad cardíaca no resecable, multisistémica o con mutaciones MAPK.
4. Manejo de soporte:
– ECMO o bypass cavoatrial en shock obstructivo agudo.
– Marcapasos permanente si hay bloqueo AV completo (reportado en pediatría con afectación del septo interauricular).
– Pericardiocentesis si hay taponamiento por derrame pericárdico masivo.

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5. ¿Existe una cura?

– No existe un medicamento único que cure todos los casos.
– La «cura» más cercana es la resección quirúrgica completa de enfermedad localizada.
– En formas sistémicas, el objetivo es la remisión prolongada o la enfermedad estable crónica con calidad de vida.
– Los inhibidores de MEK (como cobimetinib) representan el avance más significativo reciente, logrando control duradero en casos previamente letales.

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6. Recomendaciones prácticas y futuras

– Estudio genético obligatorio: Si hay enfermedad progresiva, solicitar paneles de mutaciones en MAPK (BRAF, KRAS, NRAS, MAP2K1) para guiar terapia dirigida.
– Evaluación multidisciplinaria: Hematología, oncología, cirugía cardíaca/torácica, dermatología y patología especializada en histiocitosis.
– Ensayos clínicos: La RDD es elegible para estudios de inhibidores de MEK/ERK en centros de referencia (ej. NIH, centros europeos de histiocitosis).

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⚠️ Aviso importante: La información anterior es de carácter educativo y basada en literatura médica actual. La RDD es una enfermedad rara que requiere manejo en centros especializados. Ningún fármaco debe iniciarse sin confirmación histológica y sin supervisión de un equipo médico experto. Si estás buscando opciones para un caso particular, la recomendación es contactar un centro de referencia en histiocitosis (como los afiliados a la Histiocyte Society).

. 2016 Feb;5(1):1–5. doi: 10.5582/irdr.2015.01047

Rosai-Dorfman disease and the heart

Kevin O’Gallagher ^1,^*, Luke Dancy ¹, Aish Sinha ¹, Daniel Sado ¹

PMCID: PMC4761578 PMID: 26989642

Summary

Rosai-Dorfman disease (RDD) is a non-malignant pathology of histiocyte proliferation. The classical clinical presentation is with painless cervical lymphadenopathy, but extranodal involvement is frequent, occurring in approximately 40% of cases. The literature was systematically reviewed to identify reported cases of RDD with cardiac involvement. Eighteen cases were identified (3 pediatric and 15 adult). In adult cardiac RDD (cRDD), three patterns of disease were noted: an intra-cardiac mass, epicardial involvement, and pulmonary artery involvement. Reported cases suggest that surgical excision of intra-cardiac masses confers a good prognosis.

Keywords: Histiocytosis, non-Langerhans, cardiac

1. Introduction

First described in 1965 (1) and subsequently characterized in 1969 (2), Rosai-Dorfman disease (RDD) is a non-malignant disease of histiocyte proliferation. Although the classical clinical presentation is with painless cervical lymphadenopathy (hence the alternative term “sinus histiocytosis with massive histiocytosis”, or SHML), extranodal involvement is frequent, occurring in approximately 40% of cases. Common sites of extra-nodal involvement include the skin, nasal cavities, and paranasal sinuses. Cardiac involvement (cRDD) has previously been documented as occurring in < 0.1% of cases (3).

The etiology of RDD is as yet poorly defined and is, in the absence of convincing evidence to the contrary, currently considered to be idiopathic. A viral cause has been postulated, either via direct infection or as a result of an exaggerated immune response to the viral agent. Human herpes virus 6 (HHV6) DNA has been detected in RDD histiocytes (4), but in other cases HBV6 has not been detected (5). Epstein-Barr virus (EBV) infection has been identified in approximately half of patients with RDD (6), but no evidence of EBV RNA has been found in isolated RDD histiocytes or lymphocytes (7). Parvovirus B19 has been found in RDD lymphocytes (but not histiocytes) (8). A genetic form of RDD — Faisalabad histiocytosis, mapped to a mutation in the SLC29A3 gene on chromosome 10q22.1 (9) — has been identified but is isolated to 3 consanguineous families.

Definitive diagnosis is by histological assessment, the two cornerstones of which are identification of emperipolesis and appropriate immunohistochemical analysis. Emperipolesis in relation to RDD refers to the presence of histiocytes containing intact lymphocytes within their cytoplasm. Emperipolesis is differentiated from phagocytosis due to the intact nature of the engulfed cell, which by definition is viable and can exit the engulfing cell without any structural or functional abnormality (10). In addition to RDD, emperipolesis is also seen in malignant disease processes, such as lymphoma, leukaemia, myelodysplasia, and myeloma. Immunohistochemical staining for S100 protein is considered diagnostic. Cells will also be positive for CD68 and negative for CD1a, helping to distinguish RDD histiocytes from Langerhans cells (11).

Management of RDD is greatly dependent on the extent and site of disease and also on the presence or absence of symptoms (12). Surgical resection is appropriate for localized disease, with radiation therapy an option for residual disease after resection. In systemic/extensive extranodal disease, first line therapy is corticosteroids. Other options include immunomodulators, and/or cytotoxic chemotherapeutic agents. Due to the infrequency of reported cases of cRDD, no current treatment algorithm has been defined. In general, RDD is considered a benign process, but extensive lymph node or cutaneous involvement can lead to disfigurement, and deaths have also been noted (13) (mortality 7% (14)). RDD tends not to have an adverse prognosis unless the disease has a profound effect on vital organs or is extensive/disseminated.

2. Literature review

The literature was systematically reviewed (in line with PRISMA guidance) to identify cases of RDD involving the heart and/or great vessels. A search was carried out via PubMed using the terms “Rosai Dorfman” and “sinus histiocytosis” combined with “heart” and “cardiac». Only English language publications were considered. Nine hundred and forty-three results were obtained. Those results yielded 17 papers describing 18 individual cases of cRDD (Table 1). Of the 18 individual cases, 3 were pediatric cases (< 16 years of age) while 15 were adult (≥ 16 years of age).

Table 1. Reported cases of cardiac involvement in Rosai-Dorfman disease.

Patient/Ref.	Age/Sex	Ethnic Origin	Symptoms at presentation	Type of cardiac involvement	Main site	Other sites	Extra-cardiac RDD	Treatment	Other pmh	Diagnostic Tool	Outcome**
1^P/(17)	12/M	A–C*	Chest pain, fever	Intra-cardiac infiltration and mass, complete heart block	IAS	RA mass, LV, aortic root	None	CRT, cardiac transplant	Sickle cell	Needle biopsy, explant biopsy	Alive 18 months post-transplant
2^P/(18)	12/M	U/c	Chest pain, fever	Intra-cardiac infiltration and mass, complete heart block	IAS	RA, LA, AV groove, aortic root+arch	LLL bronchus, oesophagus, posterior mediastinum, renal	Pacemaker, conservative treatment	Sickle cell	Needle biopsy, PET-CT	Alive
3^P/(19)	14/M	A–C*			Tricuspid, pulmonary valve			Multiple surgical procedures and radiation therapy		CT, cMR, PET-CT, CT-guided biopsy, excision biopsy	Death from disease progression, autopsy
4^A/(20)	27/M	A–C*	Palpitations	Intra-cardiac mass	LA	None	Mediastinal lymphadenopathy	Excision of mass			Alive
5^A/(21)	55/M	u/c	Atypical chest pain	Intra-cardiac mass	LA	LV, ascending aorta, SVC	Lungs, femur	No specific treatment	Concurrent necrotizing pneumonia	CT guided lung biopsy, VATS biopsy, surgical cardiac biopsy,	Stable
6^A/(22)	69/M	u/c	Incidental findings	Pericardial mass	Pericardium, epicardial LV surface with infiltration of myocardium	None	None	Surgical excision	Bronchitis, hypertension, gout	CT, PET-CT	Alive
7^A/(23)	62/M	u/c	Atypical chest pain, SOB	Intra-cardiac mass	RA	Invasion of IAS and RV	None	Surgical excision (incomplete)	None	Echo, CT, cMR, excision biopsy	Alive
8^A/(24)	40/M	A–C*	Edema, night sweats, weight loss, ARDS	Intra-cardiac mass	RA			N/a	CMML	Post-mortem diagnosis	Death (from other causes)
9^A/(24)	57/F	Caucasian	Atypical chest pain	Intra-cardiac mass	RA		Mediastinal lymphadenopathy	Conservative, corticosteroids,		MRI mediastinal LN biopsy, endomyocardial biopsy	Alive No change in size of mass after 2 years
10^A/(25)	60/M	u/c	SOB, fatigue	Intra-cardiac mass	RA	Invasion of RA wall	None	Surgical excision	Bilateral RAS, meningioma	Echo, CT, excision biopsy	Alive
11^A/(26)	61/M	u/c	Chest pain, SOB, atrial flutter, hypotension	Intra-cardiac mass	RA	Invasion of RA wall	None	Surgical excision	Retroperitoneal fibrosis, bilateral hydronephrosis, meningioma, hypertension, hypercholesterolaemia	Excision biopsy	Alive
12^A/(27)	29/M	u/c	Palpitations	Intra-cardiac mass	LV	Invasion of LV	None	Intra-operative biopsy with subsequent excision	Cocaine use	Echo, CT, cMR	Alive
13^A/(28)	51/F	u/c	Chest pain, SOB, edema, recurrent pericardial effusion	Recurrent pericardial effusion, Epicardial infiltration	Epicardium	None	Pleura, lungs, mediastinum, colon	Corticosteroids, repeated pericardial drainage	None	Post-mortem	Dead
14^A/(29)	51/F	u/c	Chest pain, SOB, edema	Recurrent pericardial effusion	Pericardium	None	Lungs, mesentery	Repeated drainage		Post-mortem	Dead
15^A/(30)	62/M		Dry cough	PA				Surgical pulmonary endarterectomy	Neuroendocrine tumour	PET-CT, endovascular biopsy	Alive
16^A/(31)	61/F	u/c	Syncope	PA mass	PA	None	None	N/a	None	Needle biopsy, post-mortem diagnosis	Died during biopsy
17^A/(32)	22/F	u/c	SOB, edema	Bilateral PA masses, right heart failure	L+R PA	Aorta, RA	Skin, mesentery	Surgical debulking	None	CT, PET-CT, excision biopsy	Alive
18^A/(33)	36/M	U/c	SOB	Main pulmonary artery, RVOT and pericardium	Main pulmonary artery	RVOT and pericardium	None	Surgical resection plus low-dose corticosteroids	None	TTE cardiac MRI. RV biopsy	Alive

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^P,

Pediatric;

^A,

Adult; A–C*, Afro-Caribbean; Outcome**, at discharge unless otherwise stated.

Two of the identified papers cited an additional reported case of cRDD (15). It was, however, impossible to obtain the full text of that report, so it has been excluded from the current analysis. A further case report was also cited (16), but it has been excluded as it was not written in English.

3. Pediatric cRDD

Of the 3 cases of pediatric cardiac involvement in RDD, 2 had very similar presentations: young male patients with sickle cell disease, presenting with chest pain and fever. Both of these patients had a mass in the interatrial septum (IAS) with infiltration of other cardiac structures. Both patients also presented with conduction disease requiring permanent pacing. Despite the similar presentations, the subsequent course was strikingly different. Patient 1 suffered from a progressive deterioration and required a cardiac transplant, while patient 2 had an indolent course. Both patients survived. The other case of pediatric cRDD involved a 14-year-old Afro-Caribbean boy with tricuspid and pulmonary valve involvement who underwent multiple surgical interventions but who ultimately died from disease progression.

4. Adult cRDD

The 15 adult cases involved 10 males and 5 females ranging in age from 22–79 years (mean 49.5 years). Ethnic origin was reported for only 3 patients, making comment impossible. Three patterns were identified for the primary reported site of cardiac involvement: an intra-cardiac mass with or without underlying infiltration, pericardial/epicardial involvement, and a pulmonary arterial mass (Figure 1). Of the 15 adult patients, 4 had pericardial/epicardial involvement, 4 had involvement of the pulmonary artery, and 9 had an intra-cardiac mass. Of those cases involving intra-cardiac masses, 2 had a mass in the left atrium (LA), 5 had a mass in the right atrium (RA), 1 had a mass in the left ventricle (LV), and 1 had a mass in the right ventricular outflow tract (RVOT). Seven cases presented with multi-focal cardiac involvement, i.e. invasion/extension beyond the reported primary cardiac involvement.

Figure 1. — Patterns of cardiac involvement in adults with Rosai-Dorfman disease.

5. Management of and outcomes for patients with cRDD

Of the 15 adult patients, 3 received corticosteroid treatment. This resulted in stabilization of disease in 2 patients. The other patient who received corticosteroids died of multi-organ failure related to cRDD. Affected tissue/the mass was excised in 7 patients with good results. Of the 4 patients with PA involvement, three had a lesion that was successfully treated. The other patient died during an invasive examination.

Five deaths in the cohort (18) were reported (1 pediatric patient and 4 adults). Of the deaths, 3 were related to the cRDD itself. One patient died of other causes while 1 patient died during an invasive biopsy procedure.

6. Discussion

Cardiac involvement in RDD is a rare manifestation of a rare disease, occurring in 0.1–0.2% of cases. The most common mode of presentation appears to be with an intracardiac mass, which in the majority of cases represents multi-focal underlying cardiac involvement. This literature review suggests that successful surgical excision of affected tissue carries a good prognosis.

This literature review has two main limitations. First, it relies on case reports, so there is very limited information on the subsequent follow-up of the patients involved. Thus, no comment can be made on the long-term clinical course, or indeed the frequency of disease recurrence in patients. Second, the condition is rare, so there are likely to be cases that have yet to be diagnosed, either due to unfamiliarity with the disease or due to lack of access to appropriate examinations.

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Isolated Cardiac Involvement in Rosai-Dorfman-Destombes Disease Causing Obstructive Shock

Angelina Marinkovic ^a,^∗, Emily Leung ^b, Collin Pryma ^c, Luke YC Chen ^a,^d, Peter Tsang ^a

PMCID: PMC12539452 PMID: 41005864

Abstract

Background

Rosai-Dorfman-Destombes disease (RDD) is a rare histiocytic disorder that classically presents with painless massive lymphadenopathy; however, extranodal disease can occur.

Case Summary

A 63-year-old patient was incidentally found to have a soft tissue mass in the left atrium on computed tomography imaging during work-up for atrial flutter. After open surgery to obtain tissue diagnosis, the patient developed shock requiring venovenous extracorporeal membrane oxygenation support. The tissue biopsy revealed the diagnosis of RDD, and the patient received rituximab, which led to substantial clinical improvement.

Discussion

We report a case of isolated cardiac RDD resulting in severe cardiac obstruction. Cardiac RDD is very rare, and a histopathologic diagnosis is required. Expert clinicopathologic correlation is required for early recognition and diagnosis.

Take-Home Messages

RDD is a rare neoplastic disease with heterogeneous presentations, including cardiac involvement. Treatment can range from surgery to systemic therapy, including immunomodulatory agents and targeted therapy for patients with a mitogen-activated protein kinase mutation.

Key words: emperipolesis, heart, histiocytosis, Rosai-Dorfman-Destombes disease

Graphical Abstract

Rosai-Dorfman-Destombes disease (RDD) is a rare group R histiocyte disorder characterized by proliferation of histiocytes within lymph node sinuses and lymphatics in extranodal sites.¹^,² The estimated prevalence is 1 in 200,000, and the disease predominantly affects children and adolescents, with a median age of diagnosis at 20 years, but it can occur at any age. RDD is often a diagnostic challenge because the clinical manifestations are diverse and accurate classification requires expert clinicopathologic correlation.³^,⁴ Patients may present with focal or diffuse multiorgan disease, ranging from incidental lesions on imaging studies to severe organ dysfunction.

Take-Home Messages

•
Cardiac involvement of RDD, although rare, has been described in case reports and case series, including our patient with isolated cardiac disease.
•
Surgical excision is often used for localized disease, whereas systemic therapy, such as steroids, immunomodulatory agents, or targeted therapy for patients with a mitogen-activated protein kinase mutation, is preferred for managing relapsed or multifocal disease.

Extranodal disease is more common in adults than the pediatrics population. Cardiac involvement in RDD is rare, occurring in 0.1% to 0.2% of patients, and is typically described in limited case reports and small case series.¹^,⁵^,⁶ Here, we present a rare case of RDD with exclusive cardiac involvement of the left atria complicated by obstructive shock requiring venovenous extracorporeal membrane oxygenation (V-V ECMO) support with excellent response to rituximab.

Case Presentation

A 63-year-old Chinese woman presented with atypical chest pain and was found to have atrial flutter (Supplemental Figure 1). She was otherwise previously healthy. Physical examination was normal. Bloodwork at baseline demonstrated a normal complete blood cell count and differential; C-reactive protein was 62.9 mg/L (normal: <3.1 mg/L), lactate dehydrogenase was 579 U/L (normal: 90-240 U/L), immunoglobulin G level was 6.2 g/L (normal: 6.7-15.2 g/L), and serum immunoglobulin G4 level was 0.322 g/L (normal: 0.052-1.25 g/L). ANA was negative, and she had hypocomplementemia, C3 of 0.35 g/L (normal: 0.8-1.80 g/L), and C4 of 0.09 g/L (normal: 0.12-0.36 g/L).

A cardiac computed tomography (CT) revealed asymmetrical soft tissue thickening of the right side of the left atrial wall and interatrial septum, extending between the right superior and inferior pulmonary veins, with mild-to-moderate narrowing of the right superior and inferior pulmonary veins (Figure 1). Cardiac magnetic resonance revealed the same soft tissue mass arising from the base of the left atrium/interatrial septum, encasing and stenosing the right-sided pulmonary veins and affecting the right atrium/superior vena cava inflow. Repeat imaging conducted a month later, including CT scans of the head, chest, abdomen, and pelvis, demonstrated enlargement of this mass with no other lesions identified. A positron emission tomography (PET) scan was subsequently performed, which revealed intense fluorodeoxyglucose (FDG) uptake (maximum standardized uptake value: 7.4) in the mass, with no other FDG-avid lesions detected (Supplemental Figure 2A).

CT Scan of the Rosai-Dorfman-Destombes Disease Mass in the Left AtriumComputed tomography (CT) scan of the chest in axial view, showing asymmetrical soft tissue thickening of the right side of the left atrium surrounding the right superior pulmonary vein causing mild-to-moderate narrowing (red circle).

The patient underwent an open surgical biopsy of the interatrial septum to obtain tissue diagnosis. After the cardiac biopsy, she developed shock because of obstruction of the inferior vena cava (IVC) at the IVC/right atrial junction, requiring V-V ECMO support, and a hemothorax requiring pigtail drain insertion. Because of the high-grade obstruction of the suprahepatic IVC, the patient underwent a cavoatrial bypass, leaving the atrial RDD mass in situ because it was deemed nonresectable.

Initial histopathologic examination of the biopsy revealed myocardial tissue with a dense inflammatory infiltrate that was expansile and destructive of myocytes, with a dense sclerosing matrix and some areas. There were many lymphocytes and plasma cells. There was no evidence of necrosis or granuloma formation and no evidence of lymphoma or sarcoma or infection. The biopsy was initially signed out as inflammatory process not yet diagnosed, with immunoglobulin G4-related disease in the differential diagnosis given the fibrosis. The biopsy was sent for review at a specialized oncology center. This review revealed large histiocytes characterized by emperipolesis of lymphocytes and plasma cells (Figure 2). By immunohistochemistry, the histiocytes were positive for CD68 and S100, and negative for CD1a and BRAF V600E. There was no significant increase in immunoglobulin G4-positive plasma cells, and no large abnormal lymphocytes, Reed-Sternberg cells, granulomata, multinucleated giant cells, or necrosis. These histopathologic findings confirmed the diagnosis of RDD. Next-generation sequencing was performed on the tissue biopsy using a focused panel of 39 genes in the mitogen-activated protein kinase extracellular signal-regulated kinase pathway. No tier I, II, or III variants were identified. Flow cytometry on the sample did not demonstrate any diagnostic immunophenotypic abnormalities.

Hematoxylin and Eosin Staining of the Interatrial MassHematoxylin and eosin at 20× magnification showing a section of the interatrial mass with fibrotic tissue fragments containing clusters of chronic inflammatory cells including histiocytes with abundant eosinophilic cytoplasm and prominent nucleoli, lymphocytes, and plasma cells.

While awaiting the pathology report, she received high-dose corticosteroids. However, she did not show any clinical improvement with steroids and subsequently developed Citrobacter koseri bacteremia, delirium, and volume overload. The steroids were discontinued after 10 days. She was treated with rituximab 375 mg/m² intravenously, which led to substantial clinical improvement. She was extubated, transferred out of the intensive care unit, and subsequently discharged home. She completed 4 weekly doses of rituximab. A repeat PET scan 1 month (Supplemental Figure 2B) after completion of therapy showed a significant therapeutic response, evidenced by reduced FDG activity in the RDD atrial mass (maximum standardized uptake value: 4.9 from 7.4). CT scans after rituximab therapy at 4, 9, and 19 months demonstrated ongoing reduction in size of the RDD atrial soft tissue thickening. Posttreatment, the patient had an electrocardiogram and a Holter monitor that demonstrated conversion of atrial flutter to sinus rhythm with right bundle branch block. The patient exhibited sustained clinical progress at the time of most recent assessment with no evidence of disease recurrence.

Discussion

We present a case of RDD manifesting as isolated cardiac involvement and resulting in severe cardiac obstruction necessitating V-V ECMO. Cardiac RDD is very rare, and reported cases involve the atria (particularly the right atrium), interatrial septum, left ventricle, and pericardium.⁶^,⁷ Presenting symptoms are variable and may include dyspnea, chest discomfort, palpitations, or arrhythmias, often without the classical constitutional features of RDD. Histopathologically, RDD is defined by the presence of large histiocytes exhibiting emperipolesis—intact lymphocytes within the cytoplasm of the histiocyte—within expanded lymph node sinuses or extranodal sites. These histiocytes characteristically stain positive for S100, CD68, and CD163, and are negative for CD1a.¹ However, the histologic features may be subtle or obscured by a nonspecific inflammatory background, often necessitating multiple biopsies to achieve a definitive diagnosis.³^,⁵ PET imaging is an important aspect of staging; the patient in this case had unifocal cardiac disease, but many patients will have subclinical FDG-avid disease in bone, lymph nodes, central nervous system, pancreas, and other organs.

Optimal systemic therapy for RDD is quite heterogeneous. Approximately 35% of patients have a mutation in a mitogen-activated protein kinase pathway gene, such as KRAS, NRAS, or MAP2K1. BRAF V600 mutations are common in other histiocyte disorders such as Langerhans cell histiocytosis and Erdheim-Chester disease, but are rarely seen in RDD. In patients with an mitogen-activated protein kinase mutation, targeted therapy with an mitogen-activated protein kinase inhibitor such as cobimetinib or trametinib can be highly effective.⁸^,⁹ A subset of patients may respond to steroids, and B-cell depletion with rituximab, as used in this case, can be an effective, low toxicity option. Cytotoxic chemotherapy and immunomodulatory therapy such as lenalidomide and dexamethasone are also used.¹⁰

Conclusions

RDD is a rare hematologic neoplasm that can involve cardiac tissue and sometimes cause severe complications. Review of biopsy specimens by pathologists with expertise in histiocytoses should be sought in patients with unexplained cardiac tissue inflammatory lesions. Early involvement of an experienced hematologist or oncologist to guide systemic therapy is crucial.

Funding Support and Author Disclosures

Dr Chen’s research is supported by a philanthropic gift from the Hsu & Taylor Family through the UBC & VGH Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Footnotes

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Appendix

For supplemental figures, please see the online version of this paper.

Appendix

Supplemental FiguresSupplemental Figure 1: Baseline ECG Demonstrating Atrial Flutter. Supplemental Figure 2: PET Scan Pre- and Post-Treatment With Rituximab

mmc1.docx^{(1.9MB, docx)}

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplemental FiguresSupplemental Figure 1: Baseline ECG Demonstrating Atrial Flutter. Supplemental Figure 2: PET Scan Pre- and Post-Treatment With Rituximab

mmc1.docx^{(1.9MB, docx)}

. 2019 Jul 5;27(4):286–287. doi: 10.4250/jcvi.2019.27.e37

A Rare Case of Cardiac Involvement in Rosai-Dorfman Disease

Nikolaos Tsigaridas ¹, Stavros Mantzoukis ^1,^✉, Konstantinos Mpakas ¹, Efstratios Troganis ², Dimitrios Patsouras ¹

PMCID: PMC6795570 PMID: 31614401

A 70-year-old female patient was transferred to our institution from a community hospital for coronary angiography after a non ST-elevation myocardial infarction. Her medical history was significant for the presence of Rosai Dorfman disease (RDD) for which was treated with low dose methylprednisolone. She had known abdominal lymphadenopathy and had also undergone right nephrectomy 5 years earlier due to right kidney involvement. At that time there was no cardiac involvement. Coronary angiography disclosed an intermediate severity stenosis of the right coronary artery and conservative management was decided. Transthoracic echocardiography revealed a sizeable mass of 4.5 × 4 cm in the right atrium showing enhancement after injection of echocardiographic contrast agent (Figure 1). Transesophageal echocardiography disclosed the presence of a right atrial mass encircling the cavity. It involved the right atrial free wall and the interatrial septum. It surrounded the ostium of the superior vena cava and the coronary sinus without causing obstruction (Figure 2). The mass was considered as the recurrence of past same disease and no other confirmative diagnostic process was made, regarding that there was no extra-nodal involvement. Due to the absence of hemodynamic abnormalities, we decided against interventional treatment and the patient was advised on periodic clinical and echocardiographic screening. NSTEMI could not be associated with RDD because the mass is not located near its right coronary artery orifice.

RDD is a very rare, non-malignant disease caused by proliferation of non-Langerhans sinus histiocytes.1) It is characterized of massive, painless and mainly bilateral cervical lymphadenopathy in childhood or early adulthood.2) Cardiac involvement is rare in RDD with only 17 cases previously reported in the English literature. Of these, the right atrium was affected in 7 while in some cases there was involvement in more than one cardiac locations.3) Treatment options include corticosteroids chemotherapy, radiotherapy and surgery local phenomena.2)

Footnotes

Conflict of Interest: The authors have no financial conflicts of interest.

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UNIBISA

NLM or the National Institutes of Health

Rosai-Dorfman disease and the heart

Summary

1. Introduction

2. Literature review

Table 1. Reported cases of cardiac involvement in Rosai-Dorfman disease.

3. Pediatric cRDD

4. Adult cRDD

Figure 1.

5. Management of and outcomes for patients with cRDD

6. Discussion

References

Isolated Cardiac Involvement in Rosai-Dorfman-Destombes Disease Causing Obstructive Shock