Intranodal palisaded myofibroblastoma (IPM) usually presents as a painless, slow-growing inguinal mass. Our review of 42 cases from 13 publications indicates that two thirds of IPMs occur between the ages of 45 and 55 years, the male-female ratio is 2:1, and there is a lack of ethnic predilection. Grossly, the IPM cut surface shows areas of hemorrhage. Five microscopic features are seen: (a) compressed remnants of lymphoid tissue at the periphery; (b) spindle cells with nuclear palisading; (c) intraparenchymal hemorrhage and erythrocyte extravasation; (d) so-called amianthoid fibers; and (e) intracellular and extracellular fuchsinophilic bodies that stain positive for smooth muscle actin. Immunohistochemically, IPM is positive for smooth muscle actin and cyclin D1 and negative for S100, glial fibrillary acidic protein, CD34, and desmin, and it shows a low proliferative index of Ki-67. Electron microscopy demonstrates features of myofibroblasts and smooth muscle cells. Excellent prognosis is seen after surgical treatment, with an approximately 6% recurrence rate and no malignant transformation.

Intranodal palisaded myofibroblastoma (IPM) is a benign lesion of the lymph node that may be derived from myofibroblasts or smooth muscle cells. It almost always arises from the inguinal lymph nodes, but occurrence within other areas such as mediastinum and submandibular lymph nodes has been reported.1 

The initial case reports of IPM were published by Deligdish et al2 in 1968 and Katz3 in 1974. These authors reported 2 cases with clinical-pathologic features consistent with IPM, although the cases were diagnosed as malignant neurilemmoma by Deligdish et al and as neurilemmoma by Katz. This lesion was not well characterized at the time and was considered to belong to the schwannoma/neurilemmoma family. From 1968 to 1989, IPM was often diagnosed as the intranodal form of schwannoma or as leiomyoma.4 

In 1989, 3 different groups published their findings of IPM, establishing the characterization of the lesion. Weiss and colleagues4 first proposed the name palisaded myofibroblastoma, although the alternate names intranodal hemorrhagic spindle-cell tumor with amianthoid fibers and solitary spindle cell tumor with myoid differentiation of the lymph node were initially used as well by Suster and Rosai5 and Lee et al,6 respectively.

Despite the different names proposed at the time, all of the authors agreed that the lesion showed both myofibroblastic and smooth muscle differentiation by electron microscopic studies. Subsequent authors tended to adapt the name palisaded myofibroblastoma because it reflected the myofibroblastic origin of the tumor, as well as the prominent palisaded spindle cells, histologically.7,8 The term intranodal was later added to form the full name intranodal palisaded myofibroblastoma, reflecting its lymph node location.9–12 In summary, the name intranodal palisaded myofibroblastoma reflects the following: myofibroblastic or smooth muscle cell origin, nuclear palisading of spindle cells, and lymph node location. Until now, approximately 40 cases have been reported in the English-language literature.9 

We reviewed 42 cases from 13 publications; the data are summarized in the Table. The gender is specified in 41 cases, with a male-female ratio of approximately 2:1. This lesion has been diagnosed at a wide range of ages, from 19 to 78 years. Twelve of the 20 patients in whom the age was reported were between 45 and 55 years of age. This implies that approximately two thirds of the patients fall within this age range. There are no reported pediatric cases.

Summary of Sex, Age, Site of Occurrence, and Outcome of 42 Patients With Intranodal Palisaded Myofibroblastoma From 13 Publications

Summary of Sex, Age, Site of Occurrence, and Outcome of 42 Patients With Intranodal Palisaded Myofibroblastoma From 13 Publications
Summary of Sex, Age, Site of Occurrence, and Outcome of 42 Patients With Intranodal Palisaded Myofibroblastoma From 13 Publications

Intranodal palisaded myofibroblastoma has been reported in multiple races, including white, African, and Asian, and seems to have no predilection for any particular race. The most common sites are the inguinal lymph nodes. All 42 patients presented with inguinal lymph node enlargement. However, one must keep in mind that IPM can occur in other lymphoid tissue including the submandibular and mediastinal regions.1 The lesion often presents as a painless and slow-growing inguinal lymph node. The patient usually notices a groin mass, but since the lesion is asymptomatic, the patient may not seek medical attention. One patient reportedly noticed a groin mass but did not have surgery until 40 years later.12 With significant enlargement, the mass often becomes painful and restricts movement.

Grossly, the cut surface may have different appearances, but the most common feature is dark red areas of hemorrhage (Figure 1). These hemorrhagic areas may be focal, multifocal, or diffuse. As an intranodal lesion, IPM grows from the interior portion of the lymph node expanding outwardly to the periphery; thus, normal lymphoid tissue is compressed to the periphery.

Figure 1.

Gross appearance of intranodal palisaded myofibroblastoma with multifocal areas of dark red hemorrhage. Figure 2. The peripheral area shows remnants of lymphoid tissue being compressed by a collagenous pseudocapsule (arrow) (hematoxylin-eosin, original magnification ×4).

Figure 1.

Gross appearance of intranodal palisaded myofibroblastoma with multifocal areas of dark red hemorrhage. Figure 2. The peripheral area shows remnants of lymphoid tissue being compressed by a collagenous pseudocapsule (arrow) (hematoxylin-eosin, original magnification ×4).

Close modal

There are 5 histological features for IPM. First, IPM, which is an intranodal lesion, grows outward, compressing the remaining lymph node parenchyma against the capsule. At this interface, we see hemorrhage and a collagenous pseudocapsule surrounding the lesion (Figure 2). Second, IPM is composed of bland-looking spindle cells with abundant areas of nuclear palisading similar to that of the antoni-A pattern seen in schwannomas (Figure 3, A). Third, areas of intraparenchymal hemorrhage and extravasation of red blood cells between spindle cells are seen (Figure 3, B).

Figure 3.

Intranodal palisaded myofibroblastoma shows features of nuclear palisading (A) and extravasation of red blood cells into the interstitial space (B) (hematoxylin-eosin, original magnification ×20). Figure 4. A, The so-called amianthoid fiber of intranodal palisaded myofibroblastoma has a stellate shape with a deeply eosinophilic center and paler periphery (hematoxylin-eosin, original magnification ×40). B, Fuchsinophilic bodies show positive staining for smooth muscle actin (diaminobenzidine chromagen, hematoxylin counterstain, original magnification ×100 under oil).

Figure 3.

Intranodal palisaded myofibroblastoma shows features of nuclear palisading (A) and extravasation of red blood cells into the interstitial space (B) (hematoxylin-eosin, original magnification ×20). Figure 4. A, The so-called amianthoid fiber of intranodal palisaded myofibroblastoma has a stellate shape with a deeply eosinophilic center and paler periphery (hematoxylin-eosin, original magnification ×40). B, Fuchsinophilic bodies show positive staining for smooth muscle actin (diaminobenzidine chromagen, hematoxylin counterstain, original magnification ×100 under oil).

Close modal

Fourth, collagenous bundles of so-called amianthoid fibers are distributed throughout the lesion, and have a darker eosinophilic center surrounded by a paler eosinophilic, stellate-shaped periphery (Figure 4, A). Originally, Suster and Rosai5 believed that these fibers strongly resembled amianthoid fibers due to their stellate-shaped periphery; however, the electron microscopic data have revealed no features of amianthoid fibers, thus the present nomenclature, so-called amianthoid fiber. A later study by Skalova et al13 demonstrated that these are in fact normal collagen fibers. These fibers are not a pathognomonic feature of IPM because other tumors also demonstrate collagenous amianthoid change.5 If amianthoid change is seen in association with other features of IPM, then the amianthoid fibers can be a very sensitive indicator of IPM, as they occur in virtually all cases. The fifth histological feature of IPM is extracellular and intracellular fuchsinophilic bodies. These stain red with trichrome stain and show positive muscle specific actin reactivity in immunohistochemical studies, especially in intracellular inclusions.10 The fuchsinophilic body is difficult to detect under light microscopy with hematoxylin-eosin stain; however, it is readily detectable with smooth muscle actin immunohistochemical stain (Figure 4, B).

Immunohistochemical Profile

Immunohistochemical studies are useful in confirming the diagnosis of IPM. Classically, the spindle cells are positive for vimentin and muscle specific actin, which is consistent with smooth muscle origin (Figure 5, A). Recently, IPM has been shown to have strong expression of cyclin D1 and a low proliferative index of Ki-679 (Figure 5, B). It is negative for neural markers such as S100 and glial fibrillary acidic protein, endothelial markers such as CD34, and desmin. Immunohistochemical study of the so-called amianthoid fibers indicates that the center of these fibers is composed of collagen type I, while the periphery is made up of collagen type III.5,13 

Figure 5.

Immnunohistochemical stains for smooth muscle actin (A) and cyclin D1 (B) (diaminobenzidine chromagen, hematoxylin counterstain, original magnification ×40). Figure 6. A, Electron microscopy shows myofibroblastic features including peripheral intracytoplasmic density of myofilaments (arrow), and well-developed rough endoplasmic reticulum (original magnification ×31 625). B, Electron microscopy shows the external lamina (larger arrow) on one side of the plasma membrane, and the thinner, darker linear subplasmalemmal density with budding caveolae (smaller arrow) (original magnification ×14 300).

Figure 5.

Immnunohistochemical stains for smooth muscle actin (A) and cyclin D1 (B) (diaminobenzidine chromagen, hematoxylin counterstain, original magnification ×40). Figure 6. A, Electron microscopy shows myofibroblastic features including peripheral intracytoplasmic density of myofilaments (arrow), and well-developed rough endoplasmic reticulum (original magnification ×31 625). B, Electron microscopy shows the external lamina (larger arrow) on one side of the plasma membrane, and the thinner, darker linear subplasmalemmal density with budding caveolae (smaller arrow) (original magnification ×14 300).

Close modal

Electron Microscopy

Electron microscopy can be used to confirm the diagnosis of IPM, but the histological features and immunohistochemical profile are sufficient to make the diagnosis. Electron microscopy shows 2 main features. First, the so-called amianthoid fiber is a collagen fiber, not an amianthoid fiber. Specifically, this fiber has smaller width than the true amianthoid fiber, ranging from 80 to 150 nm versus 280 to 1000 nm.13,14 

Second, the spindle cell's ultrastructures have features consistent with myofibroblastic and smooth muscle cell differentiations.4,14 The nucleus has irregular contours and occasional cytoplasmic intranuclear pseudoinclusions due to cytoplasmic invagination. The scanty cytoplasm contains moderately developed to well-developed rough endoplasmic reticulum, few mitochondria, and focal densities believed to be smooth muscle myofilaments (Figure 6, A). These features signify myofibroblastic differentiation. On the other hand, 3 main features are seen at the plasma membrane, indicating smooth muscle differentiation (Figure 6, B). The external lamina forms a light linear density along the opposite side of the cytoplasm, while the subplasmalemmal density forms a denser, thinner linear density along the cytoplasmic side. Closely associated with the subplasmalemmal densities are caveolae, which appear as round, light densities budding from the subplasmalemmal densities.

Pathogenesis

Weiss et al4 proposed that IPM may be derived from myofibroblasts or smooth muscle cells of the lymph node blood vessels. The definitive origin of IPM has remained elusive for the following reasons. First, both myoid cells, which are believed to give rise to lymph node blood vessels, and myofibroblasts are found in higher concentrations in inguinal lymph nodes than in other lymph nodes.4,9 Thus, these 2 cell lines have an equal chance of giving rise to IPM. Second, the immunohistochemical and electron microscopic studies show features of both myofibroblasts and smooth muscle cells. The features consistent with myofibroblastic origin include actin positivity by immunohistochemistry and the presence of rough endoplasmic reticulum and intracytoplasmic densities of smooth muscle myofilaments by electron miscroscopy.13 The features consistent with smooth muscle cell origin include the absence of fibronexus junctions, the absence of numerous rough endoplasmic reticula in abundant cytoplasm, and the presence of external lamina with subplasmalemmal density associating with caveolae. The bottom line is that IPM most likely arises from either smooth muscle cells or myofibroblasts.

Kleist et al9 described a case of IPM with high expression of cyclin D1 in approximately 50% of the spindle cells and further demonstrated the following molecular findings. In the tested loci of the CCND1 gene coding for cyclin D1, there is no loss of heterogeneity, no amplification of CCND1, and no allelic loss. These findings are significant because they suggest that cyclin D1 plays a role in promoting the growth of IPM due to its high expression, in the absence of genetic disturbances. These findings prompt us to review the basic function of cyclin D1 in the normal cell cycle. In in vitro experiments with mammalian cells, the cell resting at G0 stage can be induced to enter mitosis by administering growth factor, which stimulates the expression of cyclin D1.15 However, the cyclin D1 protein and its mRNA are unstable and are quickly degraded. But if one keeps providing growth factor, cyclin D1 mRNA continues to be transcribed, cyclin D1 protein continues to be produced, and mitosis persists. This observation tells us that growth factor or a similar factor may be the determining factor in maintaining a high level of cyclin D1, thus promoting cell growth. In fact, the absence of DNA abnormalities in the CCND1 gene as demonstrated by Kleist et al further eliminates the possibility that an abnormal CCND1 gene leads to a high cyclin D1 level. It is possible that a factor functionally similar to growth factor stimulates the spindle cells in IPM, leading to high cyclin D1 expression, thus promoting tumor growth.

Differential Diagnosis

Because IPM is a spindle cell tumor, the list of differential diagnoses for IPM includes a wide range of soft tissue tumors. Histological features help us narrow the differential diagnoses to the following lesions: schwannoma, Kaposi sarcoma (KS), hemangioendothelioma, and metastatic tumors.

Spindle cells with nuclear palisading may be consistent with a schwannoma. Schwannomas occur in areas innervated by peripheral nerves because they arise from the Schwann cell of the nerve sheath. Peripheral nerves do not innervate lymph nodes; thus schwannoma is very unlikely to occur within the lymph node. If there is any doubt, S100 is useful, staining positive in schwannoma and negative in IPM.

Extravasation of erythrocytes into interstitial areas may be suggestive of KS. Furthermore, the fuchsinophilic bodies of IPM can look like the hyaline globules of KS, occuring in clusters with individual bodies smaller in size than red blood cells. However, a history of immunocompromised status and/or the human herpesvirus 8 polymerase chain reaction assay should be sufficient to distinguish KS. Furthermore, nuclear palisading and amianthoid-like changes are not features of KS.

Extensive hemorrhage and spindle cell proliferation raise the possibility of hemangioendothelioma, which could occur in the lymph node. Endothelial markers such as CD31, CD34, and factor VIII should aid in this differentiation because they are positive in hemangioendothelioma and negative in IPM.

Because IPM is a spindle cell lesion of the lymph node, one must rule out the possibility of metastases from malignant melanoma, carcinoma with pseudosarcomatous features, and sarcoma. Clinical history of primary tumors and an appropriate immunohistochemical profile should be obtained to identify these metastatic tumors.

Since IPM usually presents as inguinal lymph node enlargement, the practicing cytologist may encounter IPM in fine needle aspiration. In fact, Martinez-Onsurbe et al16 remind us to keep IPM in our differential list when examining a fine-needle aspiration specimen from an inguinal lymph node. They report 2 features suggestive of IPM including (1) a moderately cellular spindle cell lesion without nuclear atypia and with fibrillary stroma; and (2) hemosiderin granules seen by Papanicolaou stain. When this diagnosis is suspected, it is best to report this lesion as a low-grade spindle cell tumor and recommend surgical excision.

Intranodal palisaded myofibroblastoma is a benign lesion with a low rate of recurrence. Thirty cases have been reported in 11 publications.2,4–7,9–12,14,17 Twenty-eight of the 30 cases showed no evidence of recurrence in follow-up ranging from 6 months to 12 years. Six percent of the cases (2/30 cases) showed evidence of local recurrence, but the recurrent tumors had the same benign histological features without evidence of malignant transformation.7,11 There are no reported cases of distant metastasis. In conclusion, IPM is a benign tumor of the lymph node that usually occurs in the groin area, with distinct histological, immunohistochemical, and electron microscopic features and a favorable prognosis.

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Poster Presentation at Texas Society of Pathologists, the 85th Annual Meeting in Houston, TX. January 20 to January 22, 2006
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The authors have no relevant financial interest in the products or companies described in this article.

The data have been presented at the Texas Society of Pathologists 85th Annual Meeting in Houston.

Author notes

Reprints: Thong Nguyen, DO, Clinical Pathology Division, University of Texas Medical Branch (UTMB), 301 University Blvd, Route #0743, Galveston, TX 77555-0743 ([email protected])