Intravascular papillary endothelial hyperplasia diagnosed by fine needle aspiration: Report of a case and cytology literature review.

Intravascular papillary endothelial hyperplasia (IVPEH) is an unusual form of intravascular endothelial proliferation. Fine needle aspiration (FNA) diagnosis of IVPEH is quite challenging and only rare reports of the cytopathological features of this entity have been published. We report a case of a 55-year-old female patient who presented with a mass on her left jaw. FNA of the mass revealed pleomorphic polygonal and spindle cells. A preliminary (onsite) cytological diagnosis of suspicious for malignancy was rendered. Subsequent cell block showed delicate papillae composed of attenuated endothelial cells overlying collagenized cores. The endothelial cells were positive for CD34 and factor VIII, supporting the cytological diagnosis of IVPEH. Surgical excision confirmed the diagnosis. To the best of our knowledge, this is the first reported case of IVPEH diagnosed by preoperative FNA.

Introduction

Intravascular papillary endothelial hyperplasia (IVPEH) is a relatively uncommon benign neoplasm of endothelial cells that has been well described in surgical pathology literature. However, there are only a few published reports on aspiration cytology of IVPEH.[1-5] All the cytopathology reports underscore the difficulty in making an accurate cytological diagnosis of this entity. The markedly atypical appearance of aspirated endothelial cells, as well as the lack of cell block material for morphological and immunohistochemical evaluation has resulted in misdiagnosis of IVPEH as malignant neoplasm on cytology aspirates.[1-5] We present a case of IVPEH diagnosed by fine needle aspiration (FNA). To the best of our knowledge, this is the first case report where a preoperative cytological diagnosis of IVPEH was rendered.

Case Report

A 55-year-old female patient presented with a progressively increasing swelling, of six months duration, on her left jaw. She also complained of left-sided otalgia. Past medical history was significant for thyroidectomy for papillary carcinoma diagnosed 2½ years ago. On examination, a tender oval mass measuring 1.5 × 1.3 × 1.2 cm was noted just anterior to the left parotid gland, overlying the inferior aspect of the masseter muscle. Patient was administered a course of oral antibiotics following which the tenderness subsided; however, the swelling persisted. Patient was referred for an ultrasound-guided FNA of the jaw swelling. Ultrasound revealed a dominant soft tissue mass in the left submandibular area, measuring 2.2 × 1.3 × 1 cm. Preliminary onsite cytological diagnosis of suspicious for malignancy was rendered. Final cytology was signed out as consistent with IVPEH. Patient underwent complete excision of the mass and final pathology revealed IVPEH.

Cytological findings

FNA was performed with a 23-gauge needle. Aspirate smears were stained with Diff Quik and Papanicolaou stains. Cell block material was also obtained. Immunohistochemical stains were performed on the cell block material using the Ventana BenchMark Ultra automated immunohistochemistry slide staining system.

The smears revealed isolated clusters of pleomorphic polygonal cells and sheets of spindle cells in a hemorrhagic background. Polygonal cells with abundant pale cytoplasm exhibited anisonucleosis, increased nuclear cytoplasmic ratio, overlapping nuclei and irregular nuclear contours [Figure 1]. Spindle cells with elongated oval nuclei and scant cytoplasm surrounded metachromatic hyaline globules and hyaline stalks [Figures 2 and 3]. No necrosis or atypical mitoses were seen. Due to patient's prior history of papillary carcinoma, we considered the cytological findings suspicious for malignancy at the time of onsite evaluation and also raised the possibility of recurrence of papillary carcinoma with anaplastic features at the time of onsite evaluation. Subsequent cell block showed characteristic features of IVPEH characterized by papillary cores lined by plump endothelial cells, adjacent to small delicate papillae [Figure 4]. The papillae were composed of attenuated endothelial cells overlying hyalinized cores. The endothelial cells maintained the polygonal or spindle shape noted in the aspirate smears. Abundant cytoplasm and large, pleomorphic nuclei were occasionally identified. No mitotic activity was noted. Immunohistochemical stains for factor VIII and CD34 performed on the cell block material outlined the endothelial cells [Figure 5]. Final cytology was reported as consistent with IVPEH.

Figure 1

Polygonal cells with abundant pale cytoplasm with anisonucleosis, increased nuclear cytoplasmic ratio, overlapping nuclei and irregular nuclear contours (Diff Quik stain, ×400)

Figure 2

Hyaline stalks with overlying spindle cell with elongated oval nuclei and scant cytoplasm (Diff Quik stain, ×200)

Figure 3

Metachromatic hyaline globules (Diff Quik stain, ×400)

Figure 4

Cell block showing anastomosing papillary cores lined by plump endothelial cells and attenuated endothelial cells overlying hyalinized cores (H and E, ×200)

Figure 5

Factor VIII immunostain outlined the endothelial cells in cell block sections (IHC, ×200)

Histological findings

The resected specimen measured 1.5 × 1.3 × 0.7 cm and revealed a hemorrhagic cut surface. The sections showed intravascular lesion with a blood clot. The characteristic features of IVPEH with numerous areas of endothelial ingrowths and delicate papillae with hyalinized cores covered by attenuated endothelial cells as noted in cell block sections were seen [Figure 6]. Loosely arranged bands of fibrous tissue were identified at the periphery of the specimen. No mitotic activity was noted. A CD34 immunohistochemical stain was performed, and it outlined the papillary structures, as well as some of the fibrous tissue at the periphery of the specimen.

Figure 6

Histological section of resected tumor showing numerous areas of endothelial ingrowths and delicate papillae with hyalinized cores covered by attenuated endothelial cells (H and E, ×200)

Discussion

In 1923, Masson described what he thought was a neoplastic process of papillary hyperplasia of endothelial cells and coined the term “vegetant intravascular hemangioendothelioma.”[6] While the exact pathophysiology is still not understood, nowadays this entity is regarded as an exuberant form of organizing thrombus.[7] It can present as a pure form involving an isolated dilated blood vessel; as a focal change in preexisting vascular lesions such as hemangiomas, vascular malformations and varices, or rarely in an extravascular location, in the setting of a hematoma.[7] It is most commonly encountered in the subcutaneous tissues of the extremities (head, neck and limbs).[8] This process has slight predilection for women and has been reported in age range of 9 months to 80 years.[8] The patient characteristic in the prior reports of IVPEH sampled by FNA and current case report are similar in terms of age, sex of the patient and location of the lesion to what has already been described in the histopathology literature [Table 1].

Table 1

Overview of previous case reports of IVPEH and comparison with present case

The most important consideration in histological differential diagnosis includes well-differentiated angiosarcoma. In contrast to IVPEH, angiosarcoma is generally extravascular, infiltrative, and shows higher degrees of histological atypia and mitotic activity.[9] The differential diagnosis in cytology specimens is broader and very challenging.[1-5] In all the prior reports, final cytological diagnosis of malignant neoplasm was rendered [Table 1]. This was mainly due to the presence of worrisome cytological features on smears, together with the lack of specific findings for diagnosis. The cases reported by Novak et al.[2] and Karim et al, [4] were diagnosed as squamous cell carcinomas after fine needle aspiration biopsy (FNAB) due to the presence of dense cytoplasm, hard cell borders, pleomorphic nuclei and prominent, sometimes multiple nucleoli. In the case reported by Suh et al,[3] pleomorphic polygonal cells were arranged in alveolar or glandular clusters, suggesting anaplastic carcinoma or adenocarcinoma. However, in view of patient's young age, they suggested a diagnosis of metastatic embryonal carcinoma. Jain et al, [5] noted cords and globular forms of hyaline material surrounded by plump endothelial cells and interpreted them as diagnostic of adenoid cystic carcinoma. Garcia-Macias et al., [1] reported two distinct populations of cells in IVPEH. One type had large nuclei, finely granular chromatin, prominent nucleoli and abundant globular cytoplasm, with occasional single cytoplasmic vacuoles. The second type of cells had spindle to oval nuclei with granular chromatin and scanty eosinophilic cytoplasm. This group identified correctly the vascular nature of the cells, but considered it to be probably malignant due to cellular atypia.

Our case showed polygonal and spindle cells, as has been reported previously.[1-5] We also noted focal acinar and papillary morphology, with the spindle cells surrounding hyaline material and hyaline stalks, similar to the ones reported by Jain et al.[5] Similar to the prior reports, based on cytological smears alone the lesion in our case was initially suspected to be malignant. Perceived anaplasia and prior history of papillary carcinoma in our case raised the possibility of recurrence of papillary carcinoma with anaplastic features. Recurrences with anaplastic features may occur in patients with prior history of papillary carcinoma or coexisting well-differentiated papillary carcinoma.[10] Unlike our case, the prior cases did not have any cell block material. The presence of classical papillary structures with hyalinized cores and demonstration of CD34 and Factor VIII positive endothelial cells in the cell block section, in our case, allowed us to reach the correct diagnosis. Surgical excision confirmed the cytological diagnosis.

To our knowledge, this is the first report of an IVPEH diagnosed by preoperative fine needle aspiration cytology. Our case underscores the importance of obtaining an adequate cell block to highlight the histological and immunohistochemical features of IVPEH that can otherwise prove to be diagnostically challenging on aspiration cytology and has a significant potential for misdiagnosis as malignant based on cytology smear findings, alone.