Rosai-Dorfman disease (RDD)/ sinus histiocytosis with massive lymphadenopathy

8/3/2019 Rosai-Dorfman disease (RDD)/ sinus histiocytosis with massive lymphadenopathy

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2011

Rosai- Dorfman Disease

(Sinus histiocytosis with massive

lymphadenopathy)

A Case ReportOral Pathology Case Report

A. V. Asanka De Silva D/05/10

F A C U L T Y O F D E N T A L S C I E N C E S - U N I V E R S I T Y O F P E R A D E N I Y A


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2Rosai- Dorfman DiseaseA Case Report

Rosai- Dorfman Disease

(Sinus histiocytosis with

massive lymphadenopathy)

A Case Report

Abstract

Rosai-Dorfman disease (RDD), otherwise

known as sinus histiocytosis with massive

lymphadenopathy is a rare disease ofunknown aetiology. First described in

1969 with painless cervical lymph node

enlargement in association with fever,

weight loss and sweating. 43% of cases

were reported extra nodally that commonly

involving skin, upper airway, and salivary

glands12

. RDD is usually seen in youngpatients. Cutaneous lesions are the

common form of extranodal diseases, but

cases of purely cutaneous lesions without

nodal or other extranodal involvement are

rare, Proliferation of large pale or foamy

histiocytes exhibiting enlarged vesicular

nuclei, prominent nucleoli, and distinctivelymphophagocytosis or emperipolesis is

the basis of the diagnosis. S-100 protein

immunophenotype is useful in confirming

the disease entity.

This case report is about a 52 yrs old male

patient presented with asymptomatic

diffuse swelling on left side pre auricular

area diagnosed as Rosai-Dorfman disease

after histopathological analysis of the

excision biopsy. Currently on follow up

after 3rd month post operatively.

Key words: emperipolesis, Rosai

Dorfman disease, sinus histiocytosis with

massive lymphadenopathy, nodal, head

and neck.

Introduction

Rosai-Dorfman disease (RDD) is a benign

systemic proliferative disorder of

histiocytes resembling the sinus histiocytes

of lymph nodes. The typical clinical

features of this disease include bilateral

painless lymphadenopathy, fever, and

polycolonal hyperglobulinaemia. The

condition with the head and neckinvolvement reported in 22% of cases,

most commonly the nasal cavity followed

by the parotid gland 10. Extranodal

involvement in 43% (500 pts) of cases,

and cutaneous lesions are the most

common form of extranodal diseases. The

disease is not confined to a particular raceor geographical area, although African

Negroes are more commonly involved

than whites9. Purely cutaneous RDD occur

rarely, particularly among Orientals10.

Nodal lesions are classified as an

inflammatory/hyperplasic disorder which

usually undergoes spontaneous regression;extranodal lesion natural history is


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associated with indolent growth and

recurrences along years or decades. It is

often confused with lymphoma.

RDD First described in 1969 with painless

cervical lymph node enlargement in

association with fever, weight loss and

sweating that commonly affects children

and adolescents. The most common sites

affected are the soft tissues of the head and

neck and the paranasal sinuses and nasal

cavity 10-4.

Case report

A 52 year old male presented to the dental

institute Colombo (DIC) with an

asymptomatic swelling on lower left sideof the cheek for 2 months duration (first

noted in November 2010). This lesion had

a sudden onset and the size of the lesion

gradually increased with time. He first got

treatment from general hospital Mathra

where FNAC was done. Microscopically

FNAC smear reveal mixed lymphoid cells

and many macrophages with engulfed

debris and, no oncocytic cells or atypical

cells were seen.The report concluded

giving differential diagnosis as reactive

lymph node and Warthins tumour. Then

he attended to Dental Institute Colombo

for his convenience. On examination firm,

non tender swelling apprx.34 cm with

demarcated margins on palpation was

noted on the left side angle of the

mandiblular region extending to sub

mandibular region.[figure 1] He had

history of leptospirosis 5years back and no

relevant family history.

Following investigations were

done.WBC/DC and blood picture were

normal, ESR was slightly elevated

(24mm/h), FNAC concluded as

inflammatory lesion and suggested

histology, Ultra sound scan left side neck

suggested Warthins tumourand MRI

suggested biopsy. There were no

radiological abnormalities. Differentialdiagnosis at surgery was tuberculosis or

lymphoma. The lesion was excised

including level one lymph nodes and sent

for histopathological examination on

27/02/2011. Mantoux test was done later

and the result was negative.

Figure 1


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Figure 2 Macroscopic appearance of the lesion

Macroscopically lesions presented as soft

nodule and a lymph node.Microscopic examination of the lymph

node [Figure 3] and the lesion revealed

partial effacement of architecture with

marked capsular fibrosis and sinus

histiocytosis. Emperipolesis of

lymphocytes and plasma cells is marked

immunehistochemically histiocytesshowed nuclear and cytoplasmic positivity

for S-100 protein [figure 4]. The

histopathological examination confirmed

the diagnosis Rosai- Dorfman Disease

After the surgery patient was on antibiotics

[IV augmentin 1.2g tds] to prevent

infection and analgesics on normalregimes. Patient is currently on review

appointments without any complaints.

Discussion

Rosai-Dorfman disease (RDD) or Sinus

histiocytosis with massive

lymphadenopathy is a rare benign systemic

proliferative disorder of unknown

aetiology. RDD belongs to broad family of

disorders known as lympho reticular

disorders which consist of 1.Reactivechanges caused by infection and

inflammation 2.Autoimmune

disorders3.Immunosupression and

4.Neoplasia. Reactive hyperplasia is one of

the disease sub types that belong to

Reactive disorders of lymph nodes which

consist of following categories1.Follicular hyperplasiain a

predominantly humoral response there is a

hyperplasia of the cortical follicles manly

composed of B lymphocytes. With

development of B cell germinal centres.

2.Parafollicular/ paracoticle hyperplasia

- in a predominantly cell mediated

response there is a hyperplasia of the

Figure 4- Immunoreactivity for S-100

Figure 3 Histiocyte cells (H&E, 40)


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paracortical follicles manly composed of T

lymphocytes. 3. Sinus hyperplasia/ sinus

histiocytosis -Certain stimuli evoke

intense phagocytic activity leading to

dilatation of subacapsular and medullary

sinuses with increased numbers and

activity of macrophages and phagocytic

lining cells. This reaction is seen in nodes

draining tissues from which endogenous

particulate matters such as lipid is

released. e.g. Necrotic tumour

It is characterised by overproduction of

histiocytes or tissue macrophages. This

condition was first described by Robb-

Smith in children and was termed as giant

cell sinus reticulosis in 19479. Sinus


lymphadenopathy (SHML) has beenrecognized as a distinct clinicopathological

entity, though first given this name by

Rosai and Dorfman in 1969. Incidences

very rare, probably less than 1000 cases

reported in the literature. The disease is

not confined to a particular race or

geographical area, although African

Negroes are more commonly involved

than whites9, 17. Although RDD may occur

in any age group, it is most frequently seen

in children and young adults14. More than

two thirds of registry patients are younger

than 10 years. Patients presenting with

isolated intracranial disease tend to be

older4. The disease is more common in

males16 ranging from 1.4:1 to 3:18, 17.

Although there is no evidence on aetiology

but viruses like Herpes virus 6 (HHV-6)

and Epstein-Barr virus (EBV) have been

suggested as potential causative agents6.

The natural history is that of a regression

and resurgence followed eventually by

complete resolution.

The clinical picture of RDD is hardly

distinguishable from malignant

lymphomas which histopathology usuallycomes as a surprise9. Head and neck

involvement has been reported in 22% of

cases; most commonly the nasal cavity

followed by the parotid gland14, the

paranasal sinuses, the nasopharynx,

submandibular glands,the larynx, the

temporal bone, the intratemporal fossa, thepterygoid fossa, the meninges and the orbit

are the other possible sites.Because of

gradual awareness of this disease entity,

more and more extranodal cases with or

without nodal involvement had been

documented. To date, extranodal Rosai-

Dorfman diseases are still on the rise and

accounted for approximately 43% of 600

registry cases, which manifested at least

one site of extranodal involvement12.

Clinical Features in most typical forms are

painless, bilateral, lymph node

enlargement in neck associated with fever,

leukocytosis, elevated erythrocytesedimentation rate in 88.5% of cases,


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polyclonal hypergammaglobulinaemia.Autoimmune hemolysis can also occur.

Most common sites involving are eyes and

ocular adnexa (especially orbit), head and

neck region, upper respiratory tract, skin

and subcutaneous tissues, skeletal system

and central nervous system. Other sites are

gastrointestinal tract, salivary glands,

genitourinary tract, thyroid, breast and

uterine cervix.

There are different clinical presentations in

RDD in head and neck region that reported

as Neck mass, facial swelling, Eye

swelling, facial pain, Headache and

Ataxia, difficulty walking and falls.

The differential diagnosis ofextranodal SHML may be a challenge15.

Comparison of classical clinical case with

this case done in table- 1Imaging (CT and

magnetic resonance imaging) may be used

to assess disease extension. If there is

cervical lymph node enlargement, FNAB

or lymph node biopsies may be useful for

the diagnosis11.The final diagnosis of RDD

usually made on characteristic

histopathological and cytological features.

La Barge et al presented a case series of 13

patients with RDD in head and neck region

in 2008 that was reported within 1997

20075. Table 3 gives the summery.

Classical cases of RDD This case

Clinical features

painless, bilateral, lymph node

enlargement

Painless Unilateral lymph

node enlargement

Fever Fever absent

leukocytosis No leukocytosis

Elevation in ESR ESR slight elevation

Autoimmune haemolysis Autoimmune haemolysis

absent

Classical histopathology In this case

Emperipolesis Emperipolesis marked

Moderately abundant plasmacells and lymphocytes

Moderately abundant plasmacells and lymphocytes

Effacement of involved organ

architecture

Partial effacement of lymph

node architecture

Positivity for CD68, alpha -1

antitrypsin,s-100, cathepsin E

Positivity being checked for

S-100 and positive results

gained.

Table-1


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The cells have histochemical and

phenotypic features of macrophages. Large

amounts of esterases and acid phosphatase

are contained by the cells. Show positivity

for CD 68 and alpha-1 antitrypsin. They

also exhibit some of the phenotypicfeatures of dendritic cells such as S100,

cathepsin E, fascin and at times CD 1a.6,

71, 8, 13. Skin biopsy non-specific unless

emperipolesis is present but lymph node

pathology is characteristic. emperipolesis

is the presence of an intact cell within the

cytoplasm of another cell.

The characteristic histopathological feature

of RDD is the proliferation of distinctive

histiocytic cells that demonstrate

lymphophagocytosis in the background a

mixed inflammatory infiltrate consisting of

moderately abundant plasma cells and

lymphocytes. As a result effacement of

involved organ architecture leading to

fibrous band formation can be noted19. No

Birbeck granules. Birbeck granules are a

characteristic microscopic finding in

Langerhans cell histiocytosis

(Histiocytosis X), which present as shaped

or "tennis-racket" cytoplasmic organelles

Deferential diagnosis Rosai-Dorfman disease

Hodgkins lymphoma Atypical monocytes, Reed-Sternberg cells +Langerhans cell histiocytosis Emperipolesis absent, Birbeck granules

identified by electron microscopy

Inflammatory pseudotumor Emperipolesis absent, positivity for S-100

protein rare

Malignant histiocytosis and lymphoma with

feature of malignant histiocytosis

Atypia, cellular pleomorphism

Hemophagocytic syndrome associated with T-cell lymphoma and/or viral infection

Lymphomatous infiltrate, lobularpanniculitis, negativity for S-100 protein

Eruptive xanthoma Emperipolesis and plasma cells absent

Generalized eruptive histiocytoma

Juvenile xanthogranuloma

Inflammatory malignant fibrous histiocytoma Atypia, cellular pleomorphism

Lepromatous leprosy Poorly defined infiltrate, plasma cells rare,

positivity for organisms on Fite stain

Table-2


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Table- 3

with a central linear density and a striated

appearance.

The differential diagnosis is made with

lymphoreticular malignancies such as

lymphomas, Hodgkin's disease, malignant

histiocytosis and monocytic leukaemia, all

of which have similar histopathological

features. Atypias in cytology and the

aggressive clinical course establish the

diagnosis in most cases. Other

histiocytoses, such as rhinoscleromas,

Wegener's granulomatosis, may also be

included in the differential diagnosis

(Table-2).Although in most patients the

extent of SHML does not appear to

determine disease outcome, recent reports

have documented that infiltrates of SHML

can cause death.

Age Sex Clinical presentation Location of the disease involvament

2.5 M Neck masses, autoimmune

haemolytic Anaemia

Nodal

5 F Neck masses Nodal38 M Neck mass Nodal

30 F Neck mass, elevated ESR Nodal and extranodal

33 M Neck mass, facial swelling Nodal and extranodal

56 M Neck masses Nodal and extranodal

75 M Left parotid and left neck

mass

Nodal and extranodal

12 F Right eye swelling Nodal and extranodal51 M Left-sided headaches Extranodal without lymphadenopathy

68 M Difficulty walking, ataxia,

falls

Extranodal without lymphadenopathy

20 F Facial pain Extranodal without lymphadenopathy

22 F Right cheek mass, sinus

disease,

no palpable lymph

enlargement

Extranodal without lymphadenopathy

19 F Facial swelling, sinus disease Extranodal without lymphadenopathy


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Management of the Rosai-Dofman disease

has no ideal protocol, because it is an

uncommon, self-limited disease,

frequently requires no therapy. When

lymph node or extranodal tissue

enlargement causes significant symptoms,

such as airway obstruction or compression

of vital organs treatment is mandatory.

Pulsone at al. reviewed 80 cases published

between 1969 and 2000; 50% of these

cases required no treatment, of which 82%

had full remission18.The role of surgery is

mostly for biopsies and to relieve

obstruction. Local recurrence is frequent

following surgical resection. The role of

radiotherapy is not well understood; some

reports have described full resolution with

this treatment, while others have shown no

response1. Steroids often resolve fever and

reduce lymph node size. Chemotherapy

has yielded controversial results. Further

investigations need to study the possible

efficacy of methotrexate and 6-

mercaptopurine. Use of alpha-interferon

has been limited because of its side effects.

Higher mortality rate is seen in patientswith immunological abnormalities at or

before presentation.

If a diagnosis of RosaiDorfman disease is

made, the patient can be initially observed

with the hope of spontaneous remission.

For tumours exclusively located in an

anatomic site amenable to surgery,

surgical excision may be considered when:

(i) the lesion persists or recurs; (ii)

cytologic findings are inconclusive; or (iii)

the patient has symptoms or desire for

removal.

References

1. Carpenter RJ III, Banks PM, McDonald TJ, Sanderson DR. Sinus


Lynphadenopathy (Rosai-Dorfman

disease): Report of a case with

respiratory tract involvement.

Laryngoscope 1978;88:1963-9.

2. Cheng SP, Jeng KS, Liu CL.Subcutaneous Rosai-Dorfman

disease: is surgical excision

justified? J Eur Acad Dermatol

Venereol. 2005;19:747-50.

3. Chu P, LeBoit PE. Histologicfeatures of cutaneous sinus

histiocytosis (Rosai-Dorfman

disease): study of cases both with

and without systemic involvement.

J Cutan Pathol 1992; 19: 201206.

4. Deodhare SS, Ang LC, and BilbaoJM. Isolated intracranial

involvement in Rosai-Dorfman

disease: a report of two cases and

a review of the literature. Arch

Pathol Lab Med 1998; 122: 161-

165.


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5. Donald V. La Barge III,Karen L.Salzman,H. Ric HarnsbergerSinus

Histiocytosis with Massive

Lymphadenopathy (Rosai-Dorfman

Disease): Imaging Manifestations

in the Head and Neck AJR:191;

December 2008;299-306.

6. Eiras JC, Schettini APM, de LimaLL. Cutaneous Rosai-Dorfman

disease ; a case report. An Bras

Dermatol. 2010;85(5):687-690

7. Eisen R N, Buckley PJ, Rosai J:Immunophenotypic

characterization of sinus


lymphadenopathy (Rosai- Dorfman

disease): Semin Diagn Patho

1990;7:74.

8. Foucar E, Rosai J, Dorfman RF.Sinus histiocytosis with massive

lymphadenopathy (Rosai-Dorfman

disease): review of the entity.

Semin Diagn Pathol 1990; 7:1973

9. GULL MOHD BHAT, SURENDERKUMAR, ATUL SHARMA, Rosai-

dorfman disease : a case report

with review of literature. Indian

journal of medical & paediatric

oncology 2004 vol. 25 no.4; 39-41.

10.H Y Huang,, C L Yang, W J ChenRosai-Dorfman Disease with

Primary Cutaneous

ManifestationsA Case

Report,Ann Acad Med Singapore

1998; 27:589-93

11.Hazarika P, Nayak DR,Balakrishnan R, Kundaje HG, Rao

PL. Rosai-Dorfman disease of the

subglottis. J Laryngol Otol 2000;

114:970-3.

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Primary Cutaneous

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13.Jaffe R,Vaughan De.,LanghoffE:Fascin and differential diagnosis

of childhood histiocytic lesions.

Pediatrol &Dev Pathol

1998;1:216.

14.Juskevicius R, and Finlay JL.Rosai-Dorfman disease of the

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Arch Pathol Lab Med 2001; 125:

1348-1350.


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15.Kroumpouzos G, Demierre M. F.Cutaneous Rosai-Dorfman

Disease: Histopathological

Presentation as Inflammatory

Pseudotumor: A Literature Review.

Acta Derm Venereol 2002; 82:

292296.

16.Lauwers GY, Perez-Atayde A,Dorfman RF, et al. The digestive

system manifestations of Rosai-

Dorfman disease (sinus


lymphadenopathy): review of 11

cases. Hum Pathol 2000; 31: 380-

385.

17.McAlister WH, Herman T, DehnerLP. Sinus histiocytosis with

massive lymphadenopathy (Rosai-

Dorfman disease). Pediatr Radiol

1990; 20:425432

18.Pulsoni A, Anghel G, Falcucci P,Matera, R Pescarmona, Ribersani

M: Treatment of Sinus

Histiocytosis Whit Massive

Lynfadenopathy (Rosai-Dorfman

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literature Review. Am J Hematol

2000; 69:61-71.

19.Siriwardena . B.S.M.S.,Tilakaratne W.M., Amaratunga

E.A.P.D, Peiris A.M.O.A case

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of the parotid gland Sri Lanka

Journal of Medicine 2004; 13(02)

41-43

AcknowledgementI would be gratefully acknowledging thecollaboration of Dr. A. M.O Peiris forproviding assistance in making thisproject a reality and Dr. Amith and Dr.Samadara Siriwardena for providingvaluable information, photographs for theproject report.I would give my sincerer gratitude forthe academic staff of the department oforal pathology Prof. W.M Thilakarathne,Prof. E. A. P. Amarathunga, Dr.Primalijayasooriya, and Dr. SamadaraSiriwardena for sharing their pricelessknowledge and precious experience.Last but not least I thank for all whocontributed including dental librarystaff, technicians.


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Rosai-Dorfman disease (RDD)/ sinus histiocytosis with massive lymphadenopathy