FNA Diagnosis of HutchisonPepper Syndrome andMetastatic Neuroblastoma:A Report of Two Cases

Dear Dr. Bedrossian:

Neuroblastoma is one of the most common extracranial

tumors of childhood.1 It usually occurs before 4 years of

age and affects both sexes.2 These neoplasms are known

to have origin from primordial neural crest and commonly

occur in the adrenal gland and retroperitoneal sympathetic

ganglia.3,4 The role of fine-needle aspiration cytology

(FNAC) in diagnosing neuroblastic tumors has been fairly

well document.5 The authors here take this opportunity to

report two cases of neuroblastoma diagnosed with the

help of FNAC, and further confirmed by immunostaining.

However, a differential diagnosis with other round cell

tumors has to be kept in mind.

Case 1

A 2-years-old male child presented with complaints of

increasing pallor, frontal swelling and proptosis for 3

months with cervical lymphadenopathy for the past 1

month. Computed Tomography (CT) brain showed ero-

sion of left temporal bone with a surrounding heterogene-

ously enhancing soft tissue mass (Fig. 1). On X-ray lytic

lesions were seen involving humerus, ribs and scapula.

Ultrasonography (USG) abdomen showed hepatomegaly

and mesenteric lymphadenopathy. No other abdominal

mass was visualized.

FNAC of cervical lymph nodes and liver (under USG

guidance) revealed groups of small round cells arranged

in rosettes around a fine fibrillar material (Homer Wright

rosettes) (Fig. 2). The entire lymph node on biopsy was

found to be replaced by a monotonous population of

small round cells (Fig. 3). Immunostaining for synapto-

physin was positive in these neoplastic cells as well as in

the fibrillar extracellular material (Fig. 4). Bone marrow

smears appeared hypercellular, and showed groups of

small round cells having scant ill-defined cytoplasm

and stippled chromatin (Fig. 5). Myelopoiesis and erythro-

poiesis were unremarkable. Thus, a final diagnosis of met-

astatic neuroblastoma was rendered, presenting as Hutchi-

son and Pepper syndrome.

Case 2

A 6-year-old boy presented with right sided abdominal

lump and right supraclavicular lymphadenopathy for 1

month. The abdominal lump was globular, firm and meas-

ured around 10 3 10 cm. USG abdomen showed a right

suprarenal mass invading into liver and retroperitoneum

with enlarged mesenteric lymph nodes. FNAC from ab-

dominal lump (USG guided) and right supraclavicular

lymph node showed similar morphology. The smears

were highly cellular, comprising of small round cells with

scant cytoplasm and nuclear moulding; forming rosettes

with central pink fibrillar material and stromal fragments,

suggestive of a small-round-cell tumor. Urinary catechol-

amines were raised (homovanillic acid [HVA]-431 mg/g

creatinine and vanillylmandelic acid [VMA]-397 mg/g

creatinine).

An excisional biopsy of the lymph node was per-

formed. Sections showed sheets of small round cells with

high nucleo-cytoplasmic ratio and stippled nuclear chro-

matin replacing the entire lymph node. Biopsy along with

the clinical and laboratory findings confirmed the diagno-

sis of neuroblastoma.

Neuroblastoma is the most common extracranial solid

tumor of childhood, accounting for 8–10% of paediatric

cancer. Over 80% are detected under the age of 4 years

and the median age at diagnosis is 21 months, with no

sex predilection.2 It arises from the primordial neural

crest and therefore can be found at any site which har-

bours sympathetic neural crest.3 These are most com-

monly known to occur in the adrenal gland and retroperi-

toneal sympathetic ganglia.4 However, they also occur at

other neural crest sites like thoraco-pulmonary, mediasti-

*Correspondence to: Siddiqui, Farhan, M.D., Department of Pathol-ogy, Jawaharlal Nehru Medical College, Aligarh Muslim University, Ali-garh, Uttar Pradesh 202002, India. E-mail: farhanfas@yahoo.com

Received 15 May 2008; Accepted 3 July 2008DOI 10.1002/dc.20935Published online in Wiley InterScience (www.interscience.wiley.com).

' 2008 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 36, No 11 843

nal, cervical and pelvic regions.6 In one of our cases, the

primary was found in adrenal glands and he had raised

urinary catecholamines, while in the other 2-years-old

child, primary could not be detected and he presented with

widespread metastasis as Hutchison-Pepper syndrome.

On FNAC, smears appear to be hypercellular with pre-

dominantly individual scattered malignant cells having a

high nucleo-cytoplasmic ratio, stippled chromatin and

scant cytoplasm. Cohesive groups of these tumor cells

with prominent nuclear moulding may also be seen, as

was seen in one of our cases. The presence of Homer-

Wright rosettes is diagnostic but they may not be present

in all the cases.6 These rosettes of neuroblastoma do not

have a central lumen.2 However, the presence of neuropil

is the most helpful feature for rendering a definitive cyto-

logic diagnosis of neuroblastoma.7

These tumors are positive for neuron specific enolase

(NSE), synaptophysin, S-100 and glial fibrillary acidic

protein (GFAP).8 Ultrastructurally, these tumor cells have

dense core neurosecretory type granules and abundant

processes containing microtubules.8

The differential diagnosis of neuroblastoma includes

Wilms’ tumor, Ewing’s sarcoma, intra-abdominal desmo-

plastic small-round-cell tumor of childhood and lympho-

blastic lymphoma. Immunostaining plays a very important

role in differentiating among these tumors. Wilms’ tumor

Fig. 1. CT scan showing erosion of left temporal bone with surroundingheterogeneously enhancing soft tissue mass with intracranial extensionextraaxially.

Fig. 2. FNA smears showing small round cells with stippled chromatinand scant cytoplasm, arranged in rosettes around fine fibrillar material(arrow) (H & E 3500).

Fig. 3. Section showing effacement of lymph node architecture andreplacement by monotonous population of small round cells, with twoHomer Wright rosettes (>) (H & E 3500).

Fig. 4. Section showing positivity to synaptophysin (3500).

ALAM ET AL.

844 Diagnostic Cytopathology, Vol 36, No 11

Diagnostic Cytopathology DOI 10.1002/dc

classically shows a triphasic pattern consisting of epithe-

lial, mesenchymal and a primitive blastemal component.

Blastemal cells show positivity to vimentin, low molecu-

lar weight cytokeratin and epithelial membrane antigen

(EMA). Ewing’s sarcoma-cells stain positively with

CD99. Intra-abdominal desmoplastic small-round-cell

tumor of childhood expresses both epithelial as well as

mesenchymal markers and therefore shows positivity to

cytokeratin, desmin and NSE. Lymphoblastic lymphoma

shows the presence of a large number of lymphoglandular

bodies in the background which are rarely seen in neuro-

blastoma, and are positive for leukocyte common antigen

(LCA) and terminal deoxy-nucleotidyl transferase (tdT).6

These commonly metastasize to liver (called as Pep-

per’s syndrome), skeletal system specially skull and orbit

(called as Hutchison’s syndrome), lymph nodes, ovary,

testis, paratesticular region, central nervous system and

bone.2 Most of the patients usually present in late stage9;

as was seen in our cases; one presented with Hutchison-

Pepper syndrome, while the other presented with metasta-

sis to supraclavicular lymph node. The prognosis of neu-

roblastoma depends on age, site of involvement and

stage.6

Hereby, we suggest that FNAC is a rapid, safe and

non-expensive diagnostic technique that yields sufficient

material and aids in the diagnosis of neuroblastoma.

Kiran Alam, M.D.

Farhan Siddiqui, M.D.*

Nazima Haider, M.D.

Veena Maheshwari, M.D.

Anshu Jain, M.D.

Arshad Khan, M.B.B.S.

Department of Pathology

Jawaharlal Nehru Medical College

Aligarh Muslim University

Aligarh, India

References1. Shaw DG. Oncology and hematology. In: Gordon I, editor. Diag-

nostic imaging in pediatrics. London: Chapman and Hall; 1987. p112–114.

2. Rosai J. Rosai and Ackerman’s surgical pathology. 9th ed. NewDelhi: Elsevier; 2004. p 1127–1132.

3. Kushner BH, Cheung NKV. Neuroblastoma-from genetic profile toclinical challenge. N Engl J Med 2005;353:2215–2217.

4. Geisinger KR, Silverman JF, Wakely PE, Jr. Pediatric cytopathology.Chicago: American Society of Clinical Pathologists; 1994.

5. Rekhi B, Gorad BD, Kakade AC, Chinoy RF. Scope of FNAC in thediagnosis of soft tissue tumors—A study from a tertiary cancer refer-ral center in India. CytoJournal 2007;4:20.

6. Singh HK, Silverman JF. Paediatric tumours. In: Orell SR, SterettGF, Whitaker D, editors. Fine-needle aspiration cytology. 4th ed.New Delhi: Elsevier; 2005. p 447–452.

7. Layfield LJ, Liu K, Dodge RK. Logistic regression analysis of smallround-cell neoplasms: A cytologic study. Diagn Cytopathol 1999;20:271–277.

8. Silverman JF, Dabbs DJ, Ganick DH, et al. Fine-needle aspirationcytology of neuroblastoma, including peripheral neuroectodermaltumor, with immunohistochemical and ultrastructural confirmation.Acta Cytol 1988;32:367–376.

9. Triche TJ, Askin FB, Kissane JM. Neuroblastoma, Ewing’s sarcoma,and the differential diagnosis of small-, round-, blue-cell tumors. In:Finegold M, editor. Pathology of neoplasms in children and adoles-cents. Philadelphia: Saunders; 1986. p 145–195.

Fig. 5. Bone marrow smears showing small round cells with stippledchromatin and ill-defined cytoplasm (MGG 3500).

FNA DIAGNOSIS OF NEUROBLASTOMA

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