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Year : 2012  |  Volume : 1  |  Issue : 4  |  Page : 257-261

Perivascular epitheliod cell tumors (PEComas): Presentation of two cases with unusual morphological features

1 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, USA
2 Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, USA

Date of Web Publication27-Dec-2012

Correspondence Address:
Guang-Yu Yang
Department of Surgical Pathology, Northwestern University, Feinberg School of Medicine, 251 East Huron Street, Feinberg 7-328, Chicago, IL 60611
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2277-8632.105108

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A distinctive group of mesenchymal tumors coexpressing markers of melanocytic and smooth muscle differentiation and presumably derived from perivascular epithelioid cells (PECs) are colligated under the rubric of PEComas. This group of tumors with classical and distinctive histological features is increasingly recognized at various sites. PEComas can occur sporadically or in association with tuberous sclerosis complex. In this report, we present two sporadic cases of PEComa, one sclerosing type arising in an unusual site, the kidney, and the other is an unusual inflammatory variant occurring in the liver. The defining histological features of the sclerosing PEComa in the kidney are bland epithelioid and spindle cells arranged in nests or fascicles surrounded by dense sclerotic stroma with calcifications. In contrast, the inflammatory PEComa in the liver showed a dense inflammatory background with scattered epithelioid cells and adipocytes. Both these tumors were positive for melanocytic markers. These isolated observations will further expand the morphological spectrum of PEComa occurring at unusual sites.

Keywords: Inflammatory PEComa, kidney, liver, mesenchymal tumors, sclerosing PEComa

How to cite this article:
Matkowskyj KA, Chen ZME, Rao S, Yang GY. Perivascular epitheliod cell tumors (PEComas): Presentation of two cases with unusual morphological features. J NTR Univ Health Sci 2012;1:257-61

How to cite this URL:
Matkowskyj KA, Chen ZME, Rao S, Yang GY. Perivascular epitheliod cell tumors (PEComas): Presentation of two cases with unusual morphological features. J NTR Univ Health Sci [serial online] 2012 [cited 2022 Jan 19];1:257-61. Available from: https://www.jdrntruhs.org/text.asp?2012/1/4/257/105108

  Introduction Top

Perivascular epithelioid cell tumors (PEComas), include a group of mesenchymal tumors containing perivascular epithelioid cells (PECs), that usually show association with blood vessel walls and coexpress immunophenotypic features of muscle and melanocytic cells. Although, no homologue of a perivascular epithelioid cell is identified, after the initial description of PEComas by Bonetti in 1992, [1] the concept of neoplasms derived from these cells is well accepted by the medical community and endorsed by World Health Organization. [2] The PEComa family of tumors includes angiomyolipoma (AML), lymphangioleiomymatosis (LAM), clear cell sugar tumors (CCST), and a large number of myomelanocytic tumors described under varied terminologies in a wide variety of locations. [3],[4],[5] Histologically, classic AML usually shows tripartite differentiation consisting of mature adipose tissue, perivascular epithelioid cells and thick-walled blood vessels. In contrast, PEComas contain epithelioid or spindle cells with clear or eosinophilic cytoplasm and may or may not contain significant adipose tissue or thick-walled vascular components. PEComas are usually immunohistochemically positive for melanocytic markers [HMB45, melan-A, microphtholmia-associated transcription factor (MITF)], myoid markers [smooth muscle actin (SMA), desmin, calponin, caldesmon], [1],[6],[7] and a subset of tumors for transcription factor E3 (TFE3) protein. [8],[9] Interestingly, unlike AML and LAM, which are often associated with tuberous sclerosis complex (TSC), such association is much less common with PEComas. [5]

Because of increased awareness of PEComas, these tumors have been increasingly recognized at usual and unusual sites including kidney, liver, skin, bone, nasal cavity, adrenal gland, appendix, etc. [10],[11],[12],[13],[14],[15] In addition, PEComas with different morphological patterns such as epithelioid, smooth muscle-predominant, adipocyte-predominant, and sclerosing types and with different molecular alterations have been described. [16],[17],[18],[19] The purpose of this article is to illustrate two cases of PEComa with unusual histological features, including the rare inflammatory variant, thus further documenting the morphological diversity of these lesions.

  Case Reports Top

Case 1

A 59-year-old female was investigated for abdominal pain and iron deficiency anemia. A computed tomography scan and magnetic resonance imaging revealed a 1.3 cm solid-appearing lesion in the upper pole of the left kidney. Imaging studies favored renal cell carcinoma. There was no significant family history or stigmata related to TSC. The patient underwent laparoscopic partial nephrectomy. Macroscopic examination showed an exophytic, white- tan, firm, well circumscribed mass measuring 1.8 cm in greatest dimension and clearly demarcated from the adjacent kidney parenchyma [Figure 1]a.
Figure 1: An exophytic, white-pink-tan globular mass measuring 1.7 cm in greatest dimension extending from the surface of the kidney. Uniform epithelioid cells with clear cytoplasm arranged in nests and trabeculae in a sclerotic background with calcifi cation (a, Hematoxylin and Eosin (HE) stain, 40×). There was no cytologic atypia, necrosis or mitosis identified (b; HE, 600×). Immunohistochemical stain reveals strong SMA (c; 600×) and MiTF (d; 600×) positivity

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Microscopically, the tumor consisted of bland epithelioid and spindle cells with clear cytoplasm and a small nucleus with inconspicuous nucleolus. No mitoses were seen. The cells are arranged in small fascicles or nests, surrounded by dense sclerotic stroma with calcifications [Figure 1]b. No fatty tissue or association of tumor cells with vessels was identified. Immunohistochemical studies revealed both epithelioid and spindle tumor cells to be positive for SMA, MITF and Melan-A [Figure 1]c and d, and negative for keratins, CD10, carbonic anhydrase IX (CA-9), HMB-45, and TFE3.

Case 2

A 64-year-old female underwent laparoscopic-assisted right liver lobe resection for a suspected hepatic adenoma with fatty change based on imaging studies. There was no family or personal history of TSC. Grossly, the tumor was well circumscribed and measured 4.2 × 3.5 × 1.7 cm. The cut surface was heterogeneous with white-tan to golden-yellow areas [Figure 2]a. No areas of necrosis were seen. No macrovascular invasion was observed. Histologically, the lesion contained a dense infiltrate of lymphocytes, plasma cells, and foamy histiocytes obscuring the underlying neoplastic process. Scattered in this inflammatory infiltrate were mature adipocytes, lipoblast-like adipocytes, and large epithelioid cells with eosinophilic cytoplasm [Figure 2]b. The epithelioid cells were uniform, and contained a round nucleus with open chromatin and a prominent nucleolus resembling ganglion cells [Figure 2]c. No mitoses, areas of necrosis or thick-walled vessels were present. At the periphery of the tumor there is sinusoidal-type of vasculature, however, in the central portion of the lesion, no prominent vasculature was present. Microscopically, the tumor was well circumscribed without infiltrative margins. The adjacent liver showed mild to moderate macrovesicular fatty change. Immunohistochemically, most of the epithelioid tumor cells were positive for HMB-45, Melan-A, and MITF [Figure 2]d. These cells were negative for anaplastic lymphoma kinase (ALK-1), hepatocyte antigen (HepPar-1), and SMA. Based on the histological and immunophenotypic features, the diagnosis of inflammatory variant of PEComa was rendered.
Figure 2: Inflammatory PEComa of the liver. Gross inspection of the lesion reveals the tumor is well circumscribed and well-delineated from the adjacent liver. The cut surface shows white-tan to golden-yellow areas. No areas of necrosis or hemorrhage are evident (a). At low power magnification, the tumor showed prominent infiltrate of lymphocytes, plasma cells and foamy histiocytes, obscuring the neoplastic cells. Scattered adipocytes are also seen (b; HE, 100×). At medium magnification epithelioid tumor cells with eosinophilic cytoplasm and round nucleus with prominent nucleolus is readily identifiable (c; HE, 200×). These neoplastic, epithelioid cells are strongly positive for microphthalmia transcription factor (d; MITF immunohistochemistry, 200×)

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  Discussion Top

Herein, we describe two morphologically unusual cases of PEComas; one occurring in the kidney and the other in the liver. Sclerosing PEComa involving the kidney, described for the first time, showed morphological features very similar to those described by Hornick et al.[17] involving mostly pararenal retroperitoneum. The only significant difference between our case and those reported by Hornick et al.[17] was the absence of a perivascular growth pattern of tumor cells. This report of a sclerosing variant of PEComa in the kidney further expands the morphologic spectrum of renal angiomyolipomas. [7],[16],[20]

The inflammatory-variant of PEComa that was observed in the liver contained an extensive lymphoplasmacytic infiltrate and foamy histiocytes imparting a golden-yellow color on gross examination, and masking the neoplastic nature of the lesion. The presence of scattered epithelioid cells and adipocytes drew our attention to the possible neoplastic nature and confirmation as PEComa by appropriate immunohistochemical studies. In this tumor, thick-walled vessels and perivascular association of tumor cells was again absent. There were two previous reports of inflammatory hepatic angiomyolipomas showing thick-walled blood vessels in addition to fat cells and smooth muscle cells. [21],[22] The difference between the current case and the other two reports were the absence of thick-walled vessels and association of tumor cells with the vessels in our case. The diagnosis of inflammatory PEComa can be very challenging because of absence of classical morphological features such as a nested arrangement of tumor cells and close association with blood vessels. The differential diagnosis of inflammatory PEComa in the liver is extensive and includes a variety of benign and malignant tumors and inflammatory processes such as inflammatory pseudotumor, inflammatory myofibroblastic tumor, IgG4-related sclerosing disease, Hodgkins and nonHodgkins lymphomas, lymphoepithelioma-like cholangiocarcinoma and hepatocellular carcinomas, follicular dendritic cell tumor, and a variety of metastatic soft tissue sarcomas with a lymphoplasmacytic infiltrate. [23],[24],[25],[26],[27],[28] Recently described intraabdominal aggressive epithelioid inflammatory myofibroblastic sarcoma may also morphologically mimic inflammatory PEComa. [29]

Although, there is no recognizable normal perivascular epithelioid cell, the concept of tumors derived from these cells is well accepted. [1],[2] The two cases presented here raise another important issue regarding the histogenesis of PEComas, due to the lack of association of tumor cells with thick- or thin-walled blood vessels. In the liver, the stellate cell has been suggested as a possible source of hepatic angiomylipoma because of a similar gene expression profile in these tumors and in stellate cells. [30] However, based on immunohistochemical, molecular, and electron microscopic studies, it has been hypothesized that neural crest-derived cells and telocytes as possible cells of origin of PEComa. [31],[32] PEComas in general behave in a benign fashion. However, a small percentage may behave aggressively with distant metastasis. The criteria that may indicate aggressive behavior include epithelioid cytological features, size larger than 5 cm, infiltrative growth pattern, pleomorphism, mitosis >1/50 high power fields, necrosis, and vascular invasion. [6],[16] However, bland cytologic features and absence of afore mentioned risk factors do not preclude metastasis, as demonstrated by Parfitt et al.[33] in a PEComa of the liver with benign histologic features and widespread metastasis. In addition to morphological features, other adjunctive markers (molecular and cytogenetic markers) are necessary for accurate prediction of the biological behavior of PEComas. In both of our patients, there is no evidence of local recurrence or metastasis 13 and 17 months after partial nephrectomy and lobectomy of liver, respectively.

  References Top

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32.Ardeleanu C, Bussolati G. Telocytes are the common cell of origin of both PEComas and GISTs: an evidence-supported hypothesis. J Cell Mol Med 2011;15:2569-774.  Back to cited text no. 32
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  [Figure 1], [Figure 2]


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