Multiple subcutaneous nodules leading to a diagnosis of metastatic neuroblastoma in an infant: A case report

Dauda E Suleiman; Zainab A Adamu; Abdullahi Mohammed

doi:10.4103/ijmh.IJMH_64_22

CASE REPORT

Year : 2023 | Volume : 28 | Issue : 1 | Page : 77-80

Multiple subcutaneous nodules leading to a diagnosis of metastatic neuroblastoma in an infant: A case report

Dauda E Suleiman¹, Zainab A Adamu², Abdullahi Mohammed³
¹ Department of Histopathology, College of Medical Sciences, Abubakar Tafawa Balewa University and Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria
² Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
³ Department of Pathology, Ahmadu Bello University and Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Submission	28-Aug-2022
Date of Decision	22-Sep-2022
Date of Acceptance	06-Nov-2022
Date of Web Publication	13-Dec-2022

Correspondence Address:
Dauda E Suleiman
Department of Histopathology, College of Medical Sciences, Abubakar Tafawa Balewa University and Abubakar Tafawa Balewa University Teaching Hospital, Bauchi
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmh.IJMH_64_22

Abstract

Neuroblastoma is a childhood malignancy with protean clinical manifestations. One rare presentation is multiple cutaneous nodules, especially in infants. We present a case of multiple cutaneous nodules as the initial presentation in an infant with metastatic neuroblastoma. The patient received chemotherapy with good response and is alive and well 5 years post diagnosis.

Keywords: Neuroblastoma, nodules, stage IV-S, subcutaneous

How to cite this article:
Suleiman DE, Adamu ZA, Mohammed A. Multiple subcutaneous nodules leading to a diagnosis of metastatic neuroblastoma in an infant: A case report. Int J Med Health Dev 2023;28:77-80

How to cite this URL:
Suleiman DE, Adamu ZA, Mohammed A. Multiple subcutaneous nodules leading to a diagnosis of metastatic neuroblastoma in an infant: A case report. Int J Med Health Dev [serial online] 2023 [cited 2023 Feb 8];28:77-80. Available from: https://www.ijmhdev.com/text.asp?2023/28/1/77/363260

Background

Neuroblastoma is a part of a group of tumors collectively referred to as “peripheral neuroblastic tumors,” which according to the International Neuroblastoma Pathology Classification also includes ganglioneuroblastoma, intermixed; ganglioneuroblastoma, nodular; and ganglioneuroma.^[1] Worldwide, these tumors are the most common childhood tumors after leukemia and brain tumors and are the most common neoplasms during the first year of life.^[1] Even though the exact events leading to tumorigenesis are poorly understood, it has been established that there is a transformation of neural crest cells secondary to some genetic or epigenetic events.^[1] The primary sites of occurrence of neuroblastoma (and other neuroblastic tumors) reflect the migration pattern of neural crest cells during fetal development and include the adrenal glands (40% of cases), the abdominal ganglia (25%), thoracic ganglia (15%), pelvic ganglia (5%), and cervical sympathetic ganglia (3%–5%). Rare tumors occur in the paratesticular region, and 1% of patients have no detectable primary tumor.^[1],[2]

The clinical behavior of neuroblastoma (and the other neuroblastic tumors) is characterized by tendencies for spontaneous regression, tumor maturation, or aggressive progression refractory to therapy.^[1],[2] These characteristics have now been linked to the molecular properties of individual tumors. Stage IV-S neuroblastoma describes a specific metastatic pattern seen almost exclusively in infants and associated with a high survival rate and spontaneous maturation and regression, often without the necessity for cytotoxic therapy.^[2] Multiple bluish to purplish cutaneous nodules producing the oft-described “blueberry muffin baby” appearance occur in at least one-third of patients less than 1-year-old and may be the initial presentation of metastatic neuroblastoma.^[3] In addition to their skin lesions, IV-S patients typically have a small tumor, usually situated in the adrenal gland, with multiple metastases to the liver and bone marrow that tend to resolve spontaneously.^[2],[3] Multiple cutaneous nodules without clinically apparent abdominal or thoracic masses are a rare initial presentation of neuroblastoma.

We present a case of neuroblastoma in an infant who initially presented with multiple cutaneous nodules.

Case Report

A 9-month-old female infant, presented to the pediatric outpatient clinic in 2017 with 3-month history of multiple subcutaneous nodules associated with progressive weight loss. The nodules were said to be painless and distributed over the trunk, abdomen, groin, and lower limbs and ranged between 2 and 5 cm in the largest diameter. There was no associated cough or difficulty in breathing, and there was no associated abdominal distension or neurologic symptoms. The child was a product of a term pregnancy and was well vaccinated for age. She is the younger of two children, and the older sibling is well and shows no signs of similar disease. On examination, the child was in no obvious distress and was well hydrated with no conjunctival pallor or peripheral lymphadenopathy. The subcutaneous nodules were distributed over the back, abdomen, groin, and the left thigh, with the largest over the groin measuring 5 × 4 cm. They are nontender with a firm consistency and freely mobile [Figure 1]. There were no organomegaly or palpable abdominal masses clinically.

Figure 1: Photographs of a child with multiple subcutaneous nodules (arrows)

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A fine needle aspiration biopsy (FNAB) was performed and revealed diffuse sheets and few aggregates of small, undifferentiated cells with dark nuclei and scant cytoplasm. The cytologic findings were suggestive of a small, round blue cell tumor, and an excisional biopsy of one of the nodules was advised for histological assessment. Subsequent histological examination of an excised nodule revealed a circumscribed nodular lesion composed of primitive small round cells frequently forming Homer-Wright pseudorosettes [Figure 2]. The tumor cells were positive for chromogranin by immunohistochemistry with the Schwannian stroma showing positivity for S100 [Figure 3]. A diagnosis of metastatic neuroblastoma to the skin was made.

Figure 2: Histological sections of subcutaneous nodules showing small, round blue cells with numerous Homer-Wright rosettes (H&E, ×200)

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Figure 3: A, The tumor cells show cytoplasmic positivity for chromogranin, and B, positive staining of the Schwannian stroma for S100

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Following the histological diagnosis, further investigations with abdominal ultrasonography and computed tomography scan revealed a localized 2 cm right adrenal mass. The patient was commenced on six courses of chemotherapy with good clinical and radiological response evidenced by a complete disappearance of subcutaneous nodules as well as regression of the adrenal mass on the repeat imaging studies. She is currently on follow-up at the pediatric oncology clinic and has no new complaints or symptoms; urinary catecholamine metabolites could not be done to monitor recurrence because of logistic and financial constraints. However, she has remained in excellent health 5 years after the diagnosis.

Discussion

Neuroblastoma is a malignant neoplasm of infancy and childhood that has been described as having “many faces” because of the assortment of clinical presentations that may occur in this disease.^[4] One of the rare presentations commonly occurring in neonates and infants is that of multiple cutaneous metastases, appearing as multiple bluish/purplish cutaneous nodules, resulting in the unfortunate moniker, “blueberry muffin baby” syndrome. It has since been recognized that other neonatal diseases may have the “blueberry muffin” appearance. This includes congenital infections, hematological disorders, and malignancies, including Langerhans cell histiocytosis.^[5]

Neuroblastoma presenting in infancy as multiple cutaneous nodules is usually associated with a small primary tumor and metastatic disease, usually confined to the skin, liver, and bone marrow; these are described as stage 4S neuroblastoma.^[6] The age of presentation for this index case was 9 months, but the subcutaneous nodules first appeared at the age of 3 months and increased in size and number over the succeeding 6 months prior to presentation. This is consistent with existing literature that reports cutaneous presentation of neuroblastoma to be most common in the first 6 months of life.^[6] The association of cutaneous neuroblastoma with small primaries, usually in the adrenal, is mirrored in this case presentation.^[6] In fact, the adrenal primary was only radiologically diagnosed after the skin excisional biopsy histology report had made the suggestion of metastatic neuroblastoma.

The index patient received chemotherapy alone and has remained in an excellent state of health approximately years after the initial diagnosis. There was a complete regression of adrenal and cutaneous masses without any clinical evidence of recurrence. This is in keeping with the favorable biology that has traditionally been ascribed to stage IV-S neuroblastoma. A pediatric cancer group study has reported a 5-year event free survival rate of 86% and a survival rate of 92%, emphasizing the excellent prognoses of these groups of patients.^[2]

Conclusions

Neuroblastoma should be considered in the clinical differential diagnosis of multiple cutaneous nodules in infants. Urinary examination for catecholamine metabolites and/or FNAB may be useful as an initial screening tool in these groups of patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient’s parents/care giver has given their consent for the images and other clinical information of their child to be reported in the journal. The parents/care giver understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Authors’ contributions

DES: conceptualization, initial drafting, and review; ZAA: review, data collection, and editing; and AM: critical review and supervision.

Ethical consideration

Ehical approval not applicable for this case report and was not received. Informed consent was received from the patient for this report.

Patient consent statement

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

References

1.	Shimada H, DeLellis R, Tissier F Neuroblastic tumours of the adrenal gland. In: Lloyd RV, Osamura RY, Kloppel G, Rosai J, editors. WHO Classification of Tumours of Endocrine Organs. 4th ed. Lyon: IARC; 2017. p. 196-203.
2.	Nickerson HJ, Matthay KK, Seeger RC, Brodeur GM, Shimada H, Perez C, et al. Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: A Children’s Cancer Group study. J Clin Oncol 2000;18:477-86.
3.	Isaacs H Jr. Cutaneous metastases in neonates: A review. Pediatr Dermatol 2011;28:85-93.
4.	David R, Lamki N, Fan S, Singleton EB, Eftekhari F, Shirkhoda A, et al. The many faces of neuroblastoma. Radiographics 1989;9:859-82.
5.	Lasek-Duriez A, Charkaluk ML, Gosset P, Modiano P [Blueberry muffin baby and Langerhans’ congenital cell histiocytosis]. Ann Dermatol Venereol 2014;141: 130-3.
6.	Jacayo NL, Davis KL Pediatric neuroblastoma: Practice essentials, pathophysiology, etiology. Medscape; 2021. Available from: https://emedicine.medscape.com/article/988284-overview. [Last accessed on 2022 Apr 13].