Non paratesticular spindle cell variant of RMS in a three year old

Introduction

Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor of myogenic origin. It is the most common childhood and adolescent sarcoma showing features of skeletal muscle differentiation. Three major variants with characteristic histologic appearances are embryonal, alveolar, and pleomorphic. Embryonal Rhabdomyosarcoma accounts for approximately 60% of all rhabdomyosarcomas. It mostly affects children below 10 years of age (mean is 7 years), adolescents and young adults and is uncommon in patients older than 40.1

Alveolar RMS is associated with a specific chromosomal translocation, t(2;13)(q35;q14), or its variant, t(1;13)(p36;q14), resulting in the formation of a fusion gene, PAX3-FKHR or PAX7-FKHR , while recurrent genetic alteration has not been identified in either embryonal and pleomorphic RMS.2

However recurrent NCOA2 gene rearrangements in a small subset of spindle cell RMS occurring in infants has been noted.3

Case

A three-year-old male child presented with rapidly enlarging abdominal mass and pain with occasional vomiting, for the past two months.

USG guided FNA was performed and smears stained with Hematoxylin & Eosin (H&E) and Giemsa.

Smears revealed moderate cellularity comprising of few round pleomorphic cells accompanied by a large proportion of spindled atypical cells. Myogenin and desmin (immunocytochemical markers for tumors of muscle origin) were positive in both components of malignant cells (Figure 1, Figure 2).

Diagnosis of ‘Round cell tumor suggestive of Rhabdomyasarcoma’ was issued.

His blood parameters and bone marrow examination showed normal hematopoiesis. Core biopsy done priorly at another institute suggested Wilms tumor.

CECT abdomen and thorax revealed a relatively well defined cystic lesion with peripheral as well as internal irregular enhancing areas in abdominopelvic region, predominantly on right side suggesting neoplastic etiology. (Figure 4)

Biopsy (Figure 3) from the mass was submitted and H&E stained sections showed a malignant mesenchymal neoplasm comprising of spindle shaped cells arranged in nodules and fascicles (>50% of neoplasm).

Individual cells were pleomorphic, having irregular elongated nuclei, scant cytoplasm, intermixed with the hyalinising bands of collagen fibres. A small population of plump to polygonal rhabdomyoblasts with prominent nucleoli and eosinophilic cytoplasm, focal necrosis, myxoid degeneration, apoptosis were also found. Mitotic count was 3-6/10 hpf.

Immunohistochemistry (IHC) resulted as

Myogenin and Desmin: Positive;

CD34, S100, beta catenin: Negative;

KI67: 30%

Figure 1

FNA: Rhabdomyoblasts Desmin Positive (400X)

Figure 2

FNA: Spindled cells Myogenin Positive (400X)

Figure 3

H&E Rhabdomyoblasts wrapped by spindled cells (H&E, 400X)

Figure 4

CECT Abdomen showing neoplastic mass on right side

Discussion

Spindle cell variant of embryonal RMS was firstdescribed in children in 1992.4 Common locations of occurrence are paratesticular and head -neck regions. Other rarely affected locations are viscera and retroperitoneum.5This variant constitutes 6% of embryonal rhabdomyosarcoma with male to female ratio of 6:16

Cytogenetic studies reveal aneuploidy with mostly whole chromosome gains as well as non-recurrent structural changes.7, 8 PAX3- and PAX7-FOXO1 fusions are virtually always absent.9

Recently, frequent and recurrent MyoD1 homozygous p.L122R mutations have been identified as pathognomonic events in adult-type spindle cell RMS10, 11, 12 and have unfavorable prognosis because of broader morphological spectrum, including sclerosing and pseudovascular types.12

MYOD1 mutant tumors also showed coexistent PIK3CA mutations.11, 13, 14 Rare tumors with sclerosing morphology were also found to harbour mutations in FGFR4 15

Mutation-negative and fusion-negative spindle cell/sclerosing rhabdomyosarcomas have a propensity to arise in genitourinary or intraabdominal locations and follow a favorable clinical course.

In paediatric population it is diagnosed at an early stage. Lymph node metastasis is seen in approximately 16% patients. 5

Major prognostic factors in these tumors are resectability, tumor size (which also correlates with resectability), histologic subtype, and tumor stage. 16

A specific grouping system for Spindle Cell-RMS has not been identified hence this variant falls into the general grouping system.

Group I completely resected tumors without lymph node involvement

Group II is composed of cases with complete resection and lymph node involvement or microscopic residual disease.

Group III includes patients with gross residual disease.

Group IV contains tumors with distant metastases.

This grouping system is used to plan additional radiation therapy for the tumor. 17

In children with any histological type of rhabdomyosarcoma, the multimodality approach has led to a cure rate of approximately 70% 18 with 95% survival at 5 years. 4

Paratesticular lesions appear to have an even better prognosis than tumors of nonparatesticular sites. 19

In adult patients there is worse prognosis with recurrence and high metastasis rate.

The differentials in this case were

Fibrosarcoma: herring bone pattern was missing, rhabdomyoblasts were present

Infantile fibromatosis: beta catenin was negative

Leiomyosarcma: Usually high grade with necrosis and mitosis and myoglobin would be negative

Rhabdomyoma: Benign tumor without necrosis or rhabdomyoblasts

Nonparatesticular regions are frequent in adults, here we are reporting such a case in a three-year-old child.

Source of Funding

None.

Conflict of Interest

None.