Intrascrotal lipoblastoma in adulthood

Abstract

This case report describes the case of a 37-year-old man that noticed an intrascrotal right mass with 1 month of evolution. During physical exam presented with a large mass at the inferior portion of the right testicle, clearly separated from the testicle, with a tender consistency and mobile. An ultrasound was performed that showed a solid and subcutaneous nodular lesion, extra testicular, heterogeneous, measuring 7.2 cm. Pelvic magnetic resonance imageMRI showed a lesion compatible with a lipoma. The patient was subjected to surgical excision of the lesion by scrotal access, having histology revealed a lipoblastoma (LB) of the scrotum. Histological diagnosis was obtained by microscopic characteristics (well-circumscribed fatty neoplasm) and immunohistochemistry (stains for CD34, S100 protein and PLAG1 were positive; stains for MDM2 and CDK4 were negative). LB is extremely rare after adolescence in any location, being this first described case of intrascrotal LB described in adulthood.

Background

Lipoblastoma (LB) is a rare benign tumour that presents mainly in infancy and early childhood (40% appear before 1 year of age and 90% before 5 years of age), with male predominance.^1–3 The diagnose of LB is extremely rare in adulthood, with some cases being described, although this is the first case described of intrascrotal location.⁴

In most cases, a mass or painless nodule is found localised in the torso or extremities. Other less common locations include head, neck, mediastinum, mesentery, epiploon, retroperitoneum and scrotum.⁵ Less than 20 cases of intrascrotal LB have been described, with an age variation at diagnosis of 7 months to 10 years.^{2 5–15}

LBs have an embryonic origin from white fat, developing as rapidly growing masses.

In the proper clinical context, histological diagnosis is uncomplicated. LB has rarely been reported in adolescents and young adults, have to be differentiated from myxoid liposarcoma or well-differentiated liposarcoma according to the grade of maturation.^{2 3}

Treatment for LB is surgery, local recurrence is common, especially when resection is incomplete.² LB does not metastasize and does not behave aggressively, having for these reasons an excellent prognosis, although it can reach large sizes due to its fast growth rate. Diagnostic difficulties may present as these lesions are almost indistinguishable from and are commonly confused with lipomas and liposarcomas.¹⁶

Case presentation

This paper presents the case of a healthy 37-year-old man, without relevant personal history and without chronic medication, who felt a right painless intrascrotal mass. The patient visited his primary care physician 2 weeks after noticing a scrotal mass, being submitted to a scrotal ultrasound. A solid subcutaneous nodular lesion, hyperechogenic measuring 7.2 cm, without connection to the testicles, localised inferiorly to the right testis (being both testicles normal), was identified. The patient was then referred to the urology department, being observed 1 month since the beginning of symptoms, referring that to his knowledge lesion size was stable. At clinical examination, external genitals did not show relevant alterations, the testicles presented in their normal position on the scrotum, without alterations in size or consistency. Inferiorly to the right testicle, an elastic/tender mass with 7 cm of size was palpable, it was mobile and clearly independent from the right testicle. There were no abdominal masses or organomegaly, no enlarged inguinal lymph nodes or hernias were palpable.

Investigations

• Blood count: without alterations.

• Testicular cancer markers (LDH, B-HCG e alfa-fetoprotein): normal.

• Pelvic MRI: oval mass, with regular well-defined limits, with 75×55×30 mm compatible with lipoma, that presents with a simple septation on its interior (figure 1).

Figure 1.

Pelvic MRI showing an oval mass, with regular well-defined limits, with 75×55×30 mm, that presents with a simple septation on its interior. (A) Sagital plane. (B) Transverse plane.

Differential diagnosis

Differential diagnosis is based on clinical criteria, biochemical results and image, being the differential histological diagnosis analysed in the discussion. Assuming that MRI has an excellent diagnostic acuity to distinguish independent paratesticular lesions,¹⁷ all data point to an extratesticular lesion, being that the main differential diagnosis is other more common paratesticular tumours.

The most likely diagnosis was lipoma. Lipoma is the most common extratesticular lesion and MRI findings were compatible with lipoma (non-enhancing mass with identical signal intensity to fat on T1-weighted and T2-weighted images).¹⁷ Other benign extratesticular tumours (adenomatoid tumour, fibrous pseudotumor, cellular angiofibroma, fibroma of the albuginea, leiomyoma) should be considered in the differential diagnosis. Adenomatoid tumour is the second most frequent extratesticular tumour, being most common between 20 and 50 years. It most commonly originates from the tail of the epididymis.^{17 18} Fibrous pseudotumor is the third most frequent extratesticular mass, corresponding to the benign proliferation of paratesticular tissues, usually associated with a prior history of trauma or infection.^{17 18} Cellular angiofibroma is a benign hypervascular lesion that can contain lipid components in its interior.¹⁷ Fibroma of the albuginea is a rare benign entity, with fibroblastic proliferation not associated with trauma or infection.¹⁸ Findings on MRI were compatible with a lesion with lipid content, making the hypotheses discussed unlikely. Finally the diagnosis of sarcoma should be also considered. Sarcomas correspond to the most common malignant lesions of the spermatic cord. Histological subtypes include liposarcoma, fibrosarcoma, rhabdomyosarcoma, malignant fibrous histiocytoma, leiomyosarcoma and undifferentiated sarcoma. The most common being rhabdomyosarcoma (40%), followed by liposarcoma and leiomyosarcoma.^{17 18} In the present context, liposarcoma was a potential diagnose.

Treatment

The patient was submitted to surgical excision of the lesion,by scrotal access. A paratesticular mass, independent of the testicle and spermatic cord, was identified. The excision was macroscopically complete.

Outcome and follow-up

Macroscopic histopathological result identified a soft tissue tumour with 7.0×4.5×3.0 cm, of extremely lobulated surface, yellowish, delimited by a thin white translucent membrane and irregular brown tissue (figure 2). Microscopic examination revealed a mature proliferation of adipocytes and spindle cells, separated by fibrovascular septa accompanied by myxoid changes.

Figure 2.

Gross appearance of lipoblastoma. The cut surface revealed a soft yellow-tan, lobulated mass.

The cells were separated in lobules by septa, and areas of immature adipocytes showing a signet-ring or multivacuolar appearance were present at the periphery (figure 3). A fine vascular network was seen. No nuclear atypia, mitoses and necrosis were seen.

Figure 3.

Microscopic appearance of lipobastoma. variable-sized signet ring univacuolated lipoblasts and multivacuolated lipoblasts admixed with adipocytes and thin-walled branching vasculature is present against myxoid backgroung (100×).

In immunohistochemistry the proliferation index evaluated, using the monoclonal antibody ki67, was inconspicuous, stains for CD34, S100 protein and PLAG1 were positive, and stains for MDM2 and CDK4 were negative. Findings were compatible with the diagnose of intrascrotal LB.

Discussion

LB is a rare tumour originating from embryonic fat, of a benign nature, most commonly of early presentation (90%, <3 years), with male predominance 3:1, dimensions usually superior to >4 cm and fast growth.^{2 5} It is usually found on the torso or extremities, existing in literature very few cases of intrascrotal location, all with ages between 7 months and 10 years of age.^{2 5–15} In paediatric age, the differential diagnosis includes: benign paratesticulars tumours (lipoma, leiomyoma, haemangioma) and malignant [rhabdomyosarcoma, liposarcoma, melanotic neuroectodermal tumour of infancy (MNTI)], as leiomyoma and MNTI normally originate from the epididymis they are easily excluded.

LB is extremely rare after adolescence in any location,¹⁹ being this the first case of intrascrotal location reported in adulthood. As such, discussing how to obtain a final diagnosis assumes an important role. Previous to histological evaluation, the most likely diagnostic hypotheses were lipoma and liposarcoma. On MRI, lower intensity on T1-weighted images has been reported with LB compared with lipoma because of its increased cellularity, allowing differentiation between LB and surrounding subcutaneous fat or lipoma. However, this distinction is of extreme difficulty and of little value in clinical practice.²⁰ Most importantly is the distinction from liposarcoma, much more common in adulthood.

Histologically, LB contains small lobules of immature and mature fat cells separated by fibrous septa with or without a myxoid stroma. The amount of fat tissue differentiation is variable, some contain mostly mature fat cells, while others are composed of large amounts of multi or univacuolated lipoblasts inside a myxoid stroma of plexiform capillaries. In sporadic cases, it may resemble brown fat.

The distinction between LB and atypical lipomatous tumour ⁄ well-differentiated liposarcoma can be made by the existence of prominent lobulation, the absence of nuclear hyperchromasia and focal myxoid stroma with plexiform vessels.^{19 20}

Diagnosis, most of the times, depends on the clinical context, especially the age of the patient, as LB occurs almost always in ages inferior to 10 years of age and liposarcoma is uncommon in ages inferior to 20 years.¹⁹ Currently, in dubious cases, genetic assessment (resorting to in-situ hybridisation analysis with fluorescence) is indicated. In approximately 70% of cases, LBs present with rearrangements of the 8q12 ⁄ PLAG1 region, resulting in transcriptional upregulation of PLAG1 oncogene, and about 20% carry a polysomy of this chromosome with or without PLAG1 rearrangement.2 3 19–21 However, it has to be highlighted that 13% of LBs lack chromosome 8 alterations and thus are FISH negative.²¹

Immunohistochemical (IHC) analysis of MDM2 and CDK4 was proposed as an indirect marker of genetic alterations, being used to support the differential diagnosis between liposarcomas and benign adipocytic tumours. However, IHC does not exactly correspond to the cytogenetic status and is not as reliable as FISH.³

In the presented clinical case, the histologic findings and the IHC analysis (namely hyperexpression of PLAG1) strongly support the diagnosis of LB and exclude the diagnosis of malignant disease. Genetic study was not conducted, which constitutes a limitation to this work.

Treatment for LB is surgery and excision must be complete, but not mutilating.¹⁶ In this clinical case, the surgical approach is controversial. In most cases of intrascrotal LB, the approach was inguinal,⁵ being this the safest in an oncological point of view. In this specific case, the physical exam and MRI showed unequivocally that the mass was independent of the testicle and the spermatic cord and suggestive of lipoma, the reason why the scrotal approach was chosen. During surgery the absence of continuity of the other structures was confirmed, and the original approach was maintained.

The prognosis is excellent, although local recurrence can occur in 0%–25%, mainly if the excision is not complete. There are no described cases of metastasis.¹⁶

Learning points.

• Lipoblastoma (LB) is a rare disease, being in most cases diagnosed before adolescence. Few cases of intrascrotal LB have been previously described, none in adulthood.

• Imagological differential diagnosis is difficult either by ultrasound or MRI, being that in adulthood the main differential diagnosis is lipoma and liposarcoma.

• The diagnosis is made by histology, which allows a distinction between LB and atypical lipomatous tumour ⁄ well-differentiated liposarcoma, aided by immunohistochemistry techniques (stains negative for MDM2 and CDK4, hyperexpression of PLAG1). In cases where doubt persists, genetic study with the presence of rearrangements of the 8q12 ⁄ PLAG1 region is useful in the diagnosis of LB.