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Intratesticular kaposiform haemangioendothelioma in adults: a report of two cases
  1. Felipe D'Almeida Costa1,
  2. Andrew L Folpe2
  1. 1Department of Anatomic Pathology, Hospital AC Camargo, Sao Paulo, SP, Brazil
  2. 2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Professor Andrew L Folpe, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA; Folpe.Andrew{at}Mayo.edu

Abstract

Kaposiform haemangioendothelioma is a very rare vascular tumour of intermediate (borderline) malignancy, typically occurring in the skin and soft tissues of the extremities in infants and children. We report two morphologically and immunophenotypically classical cases occurring in the testicular parenchyma of old adults, review the literature on vascular tumours of the testis and discuss the differential diagnosis of these unusual cases.

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Introduction

Kaposiform haemangioendothelioma (KHE) is a very rare, distinctive vascular neoplasm of intermediate (borderline) malignancy, occurring chiefly in infants and children.1–3 KHE typically presents as a large, vascular-appearing neoplasm of the skin and deep soft tissues of the extremities, head or neck and retroperitoneum.3–5 This tumour is associated in a significant number of cases with consumptive coagulopathy (Kasabach–Merritt Phenomenon, KMP), which may result in patient mortality.3–7 Although KHE may be difficult to resect completely, metastasis is exceedingly rare, with only a single reported case, to perinodal soft tissue.5 A small number of KHEs have been reported in adults, sometimes involving unusual locations such as the breast, tongue and spleen, in addition to more common cutaneous locations.5 ,8–14

Herein we report two cases of KHE involving the testicular parenchyma in old adults, representing to the best of our knowledge the first detailed descriptions of this rare tumour in this unusual location. The clinical features of one of these cases have recently been reported in abridged form in an online urology journal.15 We review the literature on vascular tumours of the testes and the differential diagnosis of KHE in this anatomical location.

Clinical, microscopic and immunohistochemical findings

Both cases were referred to one of us (ALF) in consultation. The tumours occurred within the testicular parenchyma of 81- and 39-year-old men, without involvement of the scrotal skin. The left and right testes were involved, respectively. Both patients were treated with orchiectomy and were felt to be disease free following surgery. Neither patient showed evidence of KMP. The cases were too recent for meaningful long-term clinical follow-up.

The morphological features of both tumours were essentially identical. Both tumours were centred in the testicular parenchyma, with infiltration in and around the seminiferous tubules (figure 1), and in one case infiltration of the tunica albuginea (figure 2). The lesions showed stromal fibrosis, a vaguely lobular proliferation of small, capillary-sized blood vessels (reminiscent of capillary haemangioma) (figure 3) and areas of solid, spindled growth, with distinctive ‘glomeruloid’ structures (figure 4). The endothelial cells were relatively uniform but hyperchromatic, mitotic activity was low and necrosis was absent (figure 5). A closer examination of the glomeruloid nodules showed platelet trapping within small, distended vessels (figure 6). On immunohistochemistry, the lesional cells were negative in both cases for GLUT-1 protein (rabbit polyclonal A3536, 1 : 200, Dako Advance Detection System, Dako Autostainer, Dako Corp, Carpinteria, California, USA) (figure 7). Immunohistochemistry for human herpes virus-8 latency-associated nuclear antigen was negative on one tested case (results not shown).

Figure 1

Testicular kaposiform haemangioendothelioma occurring in an 81-year-old patient showing infiltrative growth around partially sclerotic seminiferous tubules.

Figure 2

Infiltration of the tunica albuginea by kaposiform haemangioendothelioma occurring in a 39-year-old patient.

Figure 3

Kaposiform haemangioendothelioma showing a mixture of lobular and solid/glomeruloid growth patterns.

Figure 4

Spindled and glomeruloid area in a kaposiform haemangioendothelioma.

Figure 5

Intravascular platelet aggregates (arrows) in kaposiform haemangioendothelioma. Intratumoural trapping of platelets is thought to represent the pathogenesis of Kasabach–Merritt syndrome in a subset of patients with this disease.

Figure 6

Hyperchromatic, spindled endothelial with rare mitotic figures in a testicular kaposiform haemangioendothelioma.

Figure 7

Absent GLUT-1 expression in kaposiform haemangioendothelioma (red blood cells serve as internal positive control).

Discussion

KHE is uncommon, with an estimated annual prevalence of approximately 0.91 case per 100 000 children in the state of Massachusetts, corresponding to approximately 678 cases per year in the USA.3 In a recent large series of KHE, reported from Boston Children's Hospital (a paediatric referral centre specialising in vascular tumours and anomalies), the median patient age at presentation with this disease was 2 months, with a slight male predominance.3 Similar findings have been reported in other series of KHE, derived from specialised pathology consultation practices.4 ,5 Only a small number of KHEs have been reported in adults5 ,8–14 although other cases have likely been reported as examples of so-called ‘tufted angioma’ (angioblastoma of Nakagawa), a morphologically similar (if not identical), KMP-associated vascular neoplasm of adolescents and young adults.6 ,16–23

Approximately 90% of patients with KHE present with a cutaneous vascular lesion, typically extending through the subcutis to involve underlying skeletal muscle; the remainder of cases present in deep locations such as the retroperitoneum and thoracic cavity.3–5 KMP, present in >50% of patients with KHE, may result in death in 12%–30% of affected patients.3 ,24 ,25 KMP is more common in cases with deep soft tissue involvement (presumably reflecting larger tumours)3 and appears to be due to platelet trapping within the lesion itself, rather than an intrinsic platelet disorder.26 The great majority of cases of KMP are associated with KHE, rather than other vascular tumour subtypes.24 KHEs do not spontaneously involute and may cause patient morbidity and mortality through locally aggressive growth and/or recurrence.4 ,5 A single case of KHE has been reported to have metastasized to perinodal soft tissue.5

Vascular tumours of the testes are exceedingly uncommon, accounting for only 9 of more than 11 000 (<0.1%) cases in the Indiana University Testicular Tumor Registry (Dr Thomas Ulbright, personal communication; Indiana University, Indianapolis, Indiana, USA). Indeed, testicular vascular tumours are sufficiently rare as to not merit discussion in the current WHO Classification of Tumours of the Urinary System and Male Genital Organs.27 The great majority of previously reported vascular tumours of the testis are haemangiomas, including capillary,28–34 cavernous,35–43 epithelioid44 and anastomosing subtypes.45 Malignant vascular tumours of the testes are rarer yet, with only five well-documented cases of primary testicular angiosarcoma (reviewed by Armah et al46) and one case of Kaposi sarcoma.47 Although there are five reports of ‘haemangioendothelioma’ of the testis, (one Dabska type, one epithelioid and three unclassified haemangioendotheliomas), careful re-review of the provided microscopic descriptions and photomicrographs from three of these cases suggests that they would be better classified as representing papillary endothelial hyperplasia,48 papillary endothelial hyperplasia occurring within a haemangioma 49 and epithelioid haemangioma.50 Interestingly, the very first report of a testicular ‘haemangioendothelioma,’ by Stein51 shows an infiltrative and partially solid proliferation that might very well represent KHE, although it is difficult to be certain. It is also tempting to speculate that some previously reported examples of testicular ‘haemangioma’ might instead represent KHE.

The differential diagnosis of testicular KHE includes capillary and anastomosing haemangiomas, as well as Kaposi sarcoma and angiosarcoma. Capillary haemangioma shows a more pronounced lobular pattern of growth, lacks solid or ‘glomeruloid’ zones, does not show platelet trapping and in infantile examples shows strong expression of GLUT-1.52 Anastomosing haemangioma is a very recently described haemangioma variant that most often involves the kidney, but may involve the testis, retroperitoneal and paravertebral locations.45 ,53 These lesions are characterised by an anastomosing proliferation of capillary-sized vessels lined by bland endothelial cells, somewhat resembling the splenic sinusoids. Although anastomosing haemangiomas may infiltrate around pre-existing structures, such as renal tubules or seminiferous tubules, they lack the solid, spindled and glomeruloid growth patterns and the endothelial hyperchromatism seen in KHE. Kaposi sarcoma consists almost entirely of spindled cells forming slit-like vascular channels, with greater cytological variability and a more myoid appearance than is seen in KHE. Additionally, visceral Kaposi sarcoma typically occurs only in the later stage of the disease, that is, in patients with known immunocompromise. Angiosarcomas show a much greater cytological atypia, mitotic activity and destructive growth than KHE.

Although the diagnosis of KHE is chiefly a histopathological one, immunohistochemistry may be of some value in difficult cases or in unusual locations. The endothelial cells of KHE express pan-endothelial markers, such as CD31, CD34 and FLI1, but are negative for juvenile capillary haemangioma-associated markers, such as GLUT-1 and Lewis Y antigen;5 these findings may be useful in the distinction of KHE from cellular juvenile capillary haemangiomas. KHEs are also commonly positive for lymphatic endothelial-associated markers, such as Prox1,54 podoplanin55 and LYVE-1.54 When the differential diagnosis of KHE includes Kaposi sarcoma, immunohistochemistry for HHV-8 LANA protein may be of value in confirming the diagnosis of Kaposi sarcoma.56

In conclusion, we have reported the clinicopathological features of two cases of testicular KHE, both involving old adults. Although extremely uncommon, KHE should be included in the differential diagnosis for testicular vascular tumours in patients of all ages. It is likely that the natural history of this rare tumour in this unusual location will be highly favourable, given the amenability of testicular tumours to complete surgical resection.

Take-home messages

  • Vascular tumours of the testes are extremely rare.

  • KHE may involve the testes of old adults.

  • Testicular KHE should be distinguished from more aggressive vascular tumours of the testes.

View Abstract

Footnotes

  • Contributors Both authors have contributed to this manuscript.

  • Competing interests None.

  • Ethics approval Mayo Clinic IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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