Hemangiopericytomas (HPCs) are relatively uncommon tumors, accounting for 2.5% of all soft tissue neoplasms.1 They primarily occur in patients as painless masses without specific clinical or radiologic features.2, 3 HPCs may arise in any part of the body but occur most commonly in the lower extremities, retroperitoneum, and the head and neck region.2, 3
Although the histologic features of HPC are well known, to our knowledge reports regarding the cytologic findings are few and have been limited to case reports and small series.4–9 In the current study we report the cytologic findings of fine-needle aspiration (FNA) biopsy of nine confirmed cases of HPC and attempt to correlate the cytologic findings with the clinical outcomes.
MATERIAL AND METHODS
- Top of page
- MATERIAL AND METHODS
Nine FNA biopsies from five patients with HPC were retrieved from the files of the Pathology Department of New York University Medical Center (Tisch and Bellevue Hospitals) between 1989–1997. All cases were confirmed after resection. One case has been reported previously.9 Five of the FNA biopsies were performed either with 25-gauge or 27-gauge needles by cytopathologists and four FNA biopsies were performed with 22-gauge needles by a radiologist using computed tomography guidance. Smears were air-dried and stained by the Diff-Quik technique (Baxter Diagnostics, McGaw Park, IL), a modified Giemsa stain or were fixed in alcohol and stained with the Papanicolaou stain or hematoxylin and eosin. In two cases additional material from the FNA biopsy was placed in 10 mL of RPMI-buffered medium for preparation of cell blocks. Surgical specimens were fixed in 10% buffered formalin, processed in the routine fashion, and embedded in semisynthetic paraffin. Five-μm sections were cut and stained with hematoxylin and eosin. Immunocytochemical studies with antibodies to S-100 protein (Dako Co., Carpinteria, CA), CD34 (BioGenex, San Ramon, CA), vimentin (BioGenex), desmin (BioGenex), and actin (Dako Co.) were performed on formalin fixed specimens using the avidin-biotin-peroxidase method in the two cases with cell block preparations and on surgical specimens in four cases. In one case, additional fresh aspirated material was fixed in 10% glutaraldehyde for electron microscopy. Electron microscopy also was performed in fresh tissue from the surgical specimens in two cases.
The aspirates were examined for the following features: 1) cellularity; 2) architecture; 3) characteristics of the cell clusters; 4) nuclear features including nuclear size and shape, chromatin pattern, and presence of nucleoli; 5) amount and character of the cytoplasm; 6) presence of mitotic figures expressed in number per 10 high-power fields (HPF); and 7) presence of necrosis. The cytologic findings were compared with the histologic findings. A histologic diagnosis of HPC was made if the tumor showed the characteristic branched vascular pattern with uniform tumor cells arranged around these dilated vascular channels3 with no other specific stromal features. Other factors assessed included foci of increased cellularity, necrosis, hemorrhage, or increased mitotic figures. Medical charts were reviewed and follow-up information was obtained for all five patients.
- Top of page
- MATERIAL AND METHODS
HPC, first described by Stout and Murray in 1942,10 is an uncommon neoplasm of the soft tissues. It may arise in the majority of body sites,2, 3, 11, 12 but more often is found in the lower extremities (in particular the thigh), followed by the retroperitoneum and the head and neck region. It is a tumor of adult life with an equal gender distribution. In the majority of instances, both the clinical and radiologic findings are nonspecific. Despite many publications regarding HPC,2, 3, 11, 12 the existence of HPC as a distinct tumor entity recently has been questioned.13 The diagnosis of this tumor can be challenging because the neoplastic cells are spindle-shaped and can be difficult to distinguish from cells of endothelial, fibroblastic, or histiocytic origin. The hallmarks of HPC include a relatively uniform population of spindle-shaped cells arranged around vascular channels, which include dilated staghorn shaped vessels. These findings are not pathognomonic and similar architectural patterns may be observed in other soft tissue neoplasms, giving evidence to current skepticism regarding the entity. We believe that a small number of tumors with the characteristic microscopic appearance of HPC and the absence of any specific differential features justifies the diagnosis.
The use of FNA biopsy in the diagnosis of soft tissue tumors remains unsettled.14–16 FNA is useful for excluding nonmesenchymal lesions such as carcinoma and lymphoma and for identifying localized infections. In establishing a diagnosis of mesenchymal neoplasm, both the sensitivity and specificity approach 96%.17 The majority of HPCs reported in the literature4, 7, 17–19 and in our study were classified correctly as mesenchymal based on the cytologic findings. This information may guide subsequent clinical management. In our study the use of electron microscopy and immunocytochemistry on FNA samples along with the cytologic findings enabled us to make the correct diagnosis in one primary tumor. In the second primary tumor additional material for ancillary studies at the time of FNA was not available; thus, a definitive diagnosis was not made. In patients with histologically documented HPC, FNA is valuable and accurate in confirming recurrent or metastatic tumor. All our patients with recurrent or metastatic HPCs were diagnosed correctly based on routine cytology alone. Obviously, review of prior specimens is critical to diagnosis.
FNA biopsy smears of HPCs usually are cellular and the perivascular proliferation of cells observed in sections are found in cytologic specimens. The neoplastic cells aggregate around capillaries, which often are branched, but dilated, staghorn vascular channels are not observed. Metachromatic basement membrane material often is observed within the cellular aggregates and in the perivascular areas. This can be highlighted by silver staining on cytologic smears and cell block preparations.7 Nickels et al.6 described the occurrence of endothelial-lined knobby projections of tumor cells in the FNAs of all their HPCs. Like other authors,5, 8 we were unable to identify such formations. The oval or fusiform neoplastic cells can be distinguished from the endothelial cells, which appear more slender and have more open chromatin. Focal acinar formations by the tumor cells have been described and may be misinterpreted as evidence for epithelial differentiation,5, 8 representing a diagnostic pitfall. Immunohistochemistry and electron microscopy are necessary to clarify the diagnosis, and these studies must exclude the several spindle cell neoplasms that show similar cytologic features.
The differential diagnosis includes soft tissue tumors, which focally may show a hemangiopericytomatous growth pattern. These include malignant fibrous histiocytoma (MFH), synovial sarcoma, mesenchymal chondrosarcoma, and leiomyosarcoma.12 In these tumors, the hemangiopericytomatous pattern occurs with other findings characteristic of these specific lesions. Nuclear pleomorphism and the presence of multinucleated giant cells favor MFH, whereas a biphasic pattern of spindle-shaped and epithelioid cells suggests synovial sarcoma. The findings of chondrocytes and chondroid matrix point to mesenchymal chondrosarcoma. Leiomyosarcoma usually contains spindle-shaped cells with blunt-ended nuclei and cytoplasmic staining for actin. Distinguishing these lesions on FNA smears may be difficult, especially in smears comprised of bland spindle-shaped cells. Lesions such as monophasic synovial sarcoma, low grade MFH, and dermatofibromasarcoma protuberans must be considered in these cases; ancillary procedures such as electron microscopy and immunocytochemistry may lead to the diagnosis of HPC. The neoplastic cells often are immunoreactive to vimentin, factor XIIIa,20 and CD3421 as observed in our cases. Such findings are nonspecific; thus, the lack of immunostaining with epithelial, endothelial, muscular, and neural markers is important in excluding other neoplasms. Ultrastructurally, the findings of pinocytotic vesicles and multilayered basal lamina separating the individual tumor cells from one another and from the endothelial cells ultrastructurally favor a diagnosis of HPC.22
In a report of 136 lesions of soft tissue, 1 of the 2 HPCs was diagnosed correctly by FNA.17 Kumar and Misra7 correctly diagnosed two aspirates of primary HPC. Similarly, HPC was diagnosed correctly in one of the two primary HPCs in our study. In other reports Rydholm et al.18 and Akerman et al.19 described two HPCs interpreted as mesenchymal tumors, not otherwise specified. In another case, a cytologic diagnois of “mesenchymal tumor” was given to a breast lump from a 40-year-old man that was proven to be an HPC.4
Pathologists have difficulty predicting the behavior of HPC based on the clinical and pathologic features. Reports of the incidence of metastasis in HPC vary from 11.7% to 56.3%,10, 14, 23 and several microscopic criteria have been described as helpful in predicting the behavior and in distinguishing benign from malignant HPCs.12 In the majority of benign cases, < 2 or 3 mitotic figures per 10 HPF generally are noted and ≥4 mitotic figures are indicative of a tumor capable of recurrence and metastases. In addition, malignant HPCs tend to be larger and more cellular and display cellular atypia with areas of necrosis.
Nickels et al.6 reported their findings in five cases of malignant HPCs on FNA biopsy. Three of their cases showed obviously malignant features including large hyperchromatic nuclei with prominent nucleoli and numerous mitotic figures. The other two cases showed only benign neoplastic cells. In another report on the cytologic features of malignant HPCs, Geisinger et al.8 described a moderate degree of pleomorphism in approximately 50% of their aspirates and the presence of numerous mitotic figures in all patients. Except for its large size, the FNA smears of a malignant HPC reported by Nguyen et al.5 resembled a benign counterpart, and malignancy could not be determined. In our study, none of the “aggresive” HPCs had identifiable mitotic figures or nuclear pleomorphism cytologically. Obviously the presence of mitotic figures and cytologic atypia are indicative of a malignant tumor, but their absence does not exclude “aggressive” behavior.
In aspirates from cellular tumors occurring in the soft tissues of the body, especially the lower extremities, the findings of relatively uniform, oval, spindle-shaped neoplastic cells around capillaries and basement membrane material in perivascular areas suggest the diagnosis of HPC. Immunocytochemistry and electron microscopy can support a original diagnosis of HPC further. FNA biopsy is an accurate procedure for confirming recurrent or metastatic tumors. The outcome of HPC can not be predicted reliably, but the significant incidence of recurrence and metastases over long periods warrants long term follow-up of patients.