Challenging Pitfalls and Mimickers in Diagnosing Anastomosing Capillary Hemangioma of the Kidney: Case Report and Literature Review

Background

Vascular tumors of the kidney are rarely diagnosed entities, despite the fact that the kidney is a highly vascular organ that receives 25% of the cardiac output [1,2]. In the early literature, Virchow was the first to describe benign hemangioma in 1867 [3]. Hemangiomas are classified into two main types: capillary and cavernous [4]. Anastomosing hemangioma is a recently described variant of capillary hemangioma. This variant is characterized by a benign neoplastic growth of capillary-sized sinusoidal anastomosing vessels that resemble splenic parenchyma with infiltrative features. This variant might be mistaken for a malignant angiosarcoma [4,5], which is a rare, aggressive vascular tumor with poor prognosis and overall survival rate of 30%. Therefore, extensive surgical re-section with widely negative margins should be considered. In 2009, Montgomery and Epstein were the first to describe this rare variant of hemangioma [1,2,4–6]. Only 29 cases in the literature have been confirmed to be anastomosing capillary hemangioma, including our presenting case [4]. To the best of our knowledge, there is no associated syndrome that has been reported with anastomosing hemangioma, including Klippel-Trenaunay and Sturge-Weber syndrome, which have been reported to show another systemic angiomatosis [4,6]. However, some papers have shown a tendency of patients with end-stage renal disease (ESRD) to develop anastomosing hemangioma [2,4]. Only one case report showed two foci of capillary hemangioma-like vascular proliferation associated with clear cell renal cell carcinoma [7]. We present our case of a 55-year-old female with a history of radical nephrectomy three years prior from a clear cell renal cell carcinoma, who then presented with contralateral renal anastomosing hemangioma, to help better understand the biological behavior and associations of anastomosing hemangioma.

Case Report

PATHOLOGIC FINDINGS:

Grossly, under proper orientation, the partial resected left nephrectomy specimen showed a demarcated but unencapsulated round mass measuring 2×1.7×1 cm. The cut surface of the mass was fleshy, and mahogany brown with a spongy texture that was abutting but not invading the renal capsule. Microscopically, sections revealed fairly capsulated neoplastic growth. The borderlines were not sharply well-defined between the tumor cells and the adjacent kidney parenchyma (Figure 2A). High power examination revealed tumor cells exhibiting cords pattern with tightly packed prominent capillary-sized vessels “sieve-like” and anastomosing sinusoidal architecture (Figure 2B). Focal areas showed edema dissecting neoplastic growth. Cellular examination showed plumped cuboidal cells, round to oval uniform cells with scant cytoplasm (Figure 2C). Some of these vessels were lined by hobnail endothelial cells. Extravasated red blood cells are seen adjacent to the tumor cells (Figure 3A). No atypical cells, multi-layering, mitosis, necrosis, or apoptotic activity were seen. Focal areas showed an infiltrative growth pattern of tumor cells. The lining stroma showed areas of hemorrhage and vascular thrombi within the tumor tissue (Figure 3B); focal sclerotic changes were seen (Figure 2D). No evidence of intracytoplasmic hyaline globules or extramedullary hematopoiesis was seen. The adjacent kidney parenchyma showed mild inflammation, atrophic glomeruli, and tubules. Immunohistochemical studies showed diffuse positive staining for endothelial markers including CD31 (Figure 3C), CD34, factor VIII (Figure 3D), and vimentin; although negative for HMB45, CD10, RCC, CK7, SMA, desmin, D2–40, AFP, glypican3, HHV8, and S100 protein. EMA and cytokeratin AE1/AE3 highlighted the entrapped renal tubules. Together the histopathologic appearance and the immunohistochemical studies of this tumor were indicative of a diagnosis of anastomosing hemangioma of the kidney. The patient had a follow-up after surgery for 12 months and showed no more complications.

Discussion

CLINICAL FINDINGS:

Anastomosing capillary hemangioma is a rare, recently described neoplasm of the kidney. Commonly it affects middle-aged adults, with an average age of 52 years (range 21–83 years) [4] with a slight male predominant 1.8 to 1 ratio [2]. Most patients are discovered incidentally or during regular follow-up and show no symptoms. Clinical findings might include abdominal pain, colicky pain, lower urinary tract symptoms, and hematuria. In one case report, the patient presented with chronic polycythemia which resolved completely after mass excision [8]. The clinical presentation of this tumor is non-specific. Unlike bladder hemangioma, renal hemangioma is not associated with tuberous sclerosis, Sturge-Weber syndrome, or Klippel-Trenaunay syndrome [4,6]. However, some studies have shown that patients with ESRD are more prone to develop renal capillary hemangioma [4,5]. The pathogenesis is not well understood, but these patients with ESRD have shown a potential to develop both epithelial and mesenchymal lesions like papillary RCC, clear cell RCC, papillary adenoma, and angiomyolipoma [2,5]. One case report of a multifocal capillary hemangioma-like vascular proliferation was associated with clear cell renal cell carcinoma [7], the authors suggested the possibility that these vascular proliferations were probably due to growth factors produced by the accompanied carcinoma [7]. Yet, the exact potential pathogenic factors are not well understood and not identified through reviewing the reported case. Overall, anastomosing hemangioma is not unique to any syndrome and can develop without any chronic disease as observed in the literature (Tables 1–3 and Figures 4, 5).

IMAGING FINDING:

It is rarely possible to establish a pre-operative diagnosis using radiological studies alone and thus, conservative management is often not considered [6]. Ultrasound examination usually reveals variable echogenicity [2,17]. Non-enhancing CT scans can show a lobulated hypo-attenuating mass, while enhanced CT imaging can demonstrate a solid, well-demarcated heterogeneous mass [11,17].

MACROSCOPIC FINDING:

Hemangiomas, in general, are mesenchymal tumors that typically favor the skin and subcutaneous soft tissue [5]. Some reports have documented their involvement in vesical organs, commonly the liver [2,5,18]. One review showed that anastomosing hemangioma showed a predilection toward the genitourinary system, particularly the kidney [2,6]. Others locations include the ovaries [14], testes, thigh, abdominal wall [16], gastrointestinal tract [18], and adrenal gland [19]. In the kidney, anastomosing hemangiomas typically involve the hilum [2,20]. Moreover, other kidney locations have been reported such as the medulla and cortex, especially in the context of ESRD [6], perinephric adipose tissue, and renal sinus [2,6]. Some of these tumors abut but do not invade the renal capsule, similar to our case. One case report showed a segmental involvement of the renal vein [1] and larger veins like the inferior vena cava [6]. However, all reported cases showed no malignant features or vascular invasion either gross or microscopic. The average size of tumors was 1.5 cm (range, 0.1–7 cm) [2]. The largest tumor size reported was 7 cm, which was discovered incidentally during follow-up exam [10]. The tumors were typically unilateral, with only four cases reported as bilateral tumors [2,14]. Multifocality was also reported in patients with nephrectomy for renal cell carcinoma [7]. The latter is usually associated with ESRD patients [2].

DIFFERENTIAL DIAGNOSIS:

The differential diagnosis includes angiosarcoma, Kaposi sarcoma, intravascular papillary endothelial hyperplasia (IPEH), and angiomyolipoma. Other less likely differential diagnoses are hemangioblastoma and glomus tumors.

It is believed that anastomosing hemangioma is a great mimicker of some tumors, most importantly capillary angiosarcoma. Both show overlapping histological features like the presence of hyaline globules and have positive immunochemistry stains for endothelial markers [2]. Angiosarcoma is an aggressive malignant neoplasm with a tendency to occur in the sixth to seventh decade of life [2]. It is often larger in size with areas of necrosis, and commonly metastasizes to the liver, lung, and bone. Histological features include infiltrative renal lesion with dissecting vascular channels exhibiting anastomosing capillary network lined by hobnail endothelium demonstrating highly atypical cells with prominent nucleoli and a high nuclear to cytoplasmic ratio. The lesion is usually rich in cellularity with increased mitotic activity [2,4,5,10,11,20]. Kaposi sarcoma is a malignant neoplasm that grows in a slit-like space and shows hyaline globules. HHV-8 is a good marker, which stains positively in Kaposi sarcoma unlike anastomosing hemangioma.

Intravascular papillary endothelial hyperplasia (IPEH) is a vascular lesion that mimics anastomosing hemangioma in its non-specific presentation together with endothelial marker positivity. However, IPEH tends to form papillary architecture lined by stratified hyperplastic endothelial lining without the formation of sinusoidal spaces seen in anastomosing hemangioma. Angiomyolipoma is a mesenchymal neoplasm of the PEComa family; which demonstrates a triphasic pattern of vascular, smooth muscle cells, and fat tissue components. The tumor stains perfectly for melanocytic markers such as HMB-45 and Melan-A, which would be negative in anastomosing hemangioma staining [2]. Hemangioblastoma shows more large cells with abundant cytoplasm, and stains specifically for S100 proteins, NSE, and inhibin [21]. Glomus tumors are usually nests and oval-shaped tumor cells which are randomly distributed around expanded capillaries, no anastomosing or hobnail endothelial cells are seen. Alpha smooth muscle actin (α-SMA) is a good stain for glomus [22,23].

Conclusions

In conclusion, anastomosing hemangioma is a rare variant of capillary hemangioma. It has a sinusoidal growth pattern which resembles splenic parenchyma. It mimics malignant neoplasms, thus, clinical and radiological examination are not enough for accurate diagnosis. Careful histopathological and immunohistochemical studies are required to establish the correct diagnosis.