EXTRAORDINARY CASE REPORT
Fibrolipomatous Hamartoma of the Nerve Arising in the Neck: A Case Report With Review of the Literature and Differential Diagnosis Lauren Philp, MD,* Karen A. Naert, MD,† and Danny Ghazarian, MB ChB, PhD†
Abstract: We report an unusual case of a fibrolipomatous hamar-
toma that arose in a nuchal nerve. Typically, fibrolipomatous hamartoma, otherwise known as a neural fibrolipoma or lipomatosis of nerve, arises in the median nerve, brachial plexus, cranial nerves, or plantar nerves. The differential diagnosis is broad and includes benign and malignant spindle cell lesions, such as spindle cell lipoma, perineurioma, and myxoid liposarcoma. We were able to identify the lesion based on the typical histology, including triphasic composition with spindle cell, neural, and adipocytic components and whorled architecture. Because of the atypical location in the neck, detailed immunohistochemical staining was performed. The lesional spindle cells were negative for SMA, CD10, CD68, EMA, S100, PGP9.5, CD34, CD56, and beta-catenin. Colloidal iron stain highlighted marked intralesional mucin deposition. This detailed immunohistochemical profile is a useful diagnostic aid and to our knowledge has not been previously described. Key Words: fibrolipomatous hamartoma of nerve, neural fibrolipoma, lipomatosis of nerve (Am J Dermatopathol 2015;37:e78–e82)
INTRODUCTION Fibrolipomatous hamartoma of nerve (FLH) is a rare benign fibroproliferative condition affecting peripheral nerves. Although the exact pathogenesis remains unknown, it is speculated that FLH is a congenital lesion.1,2 Clinically it presents as a gradually expanding mass, most commonly occurring in the median nerve followed by the ulnar, radial, peroneal, and cranial nerves.3 This fibrofatty overgrowth generally presents in children and young adults and is frequently associated with macrodactyly.4 Other symptoms can include pain, paresthesias, and compression neuropathies. However, the most common clinical presentation is that of a soft, mobile, slowly expanding painless mass.1 Histologically, these lesions show a concentric epineural and perineural expansion with From the *Department of Plastic Surgery, University of Toronto, Toronto, Ontario, Canada; and †Department of Laboratory Medicine and Pathobiology, University of Toronto and University Health Network, Toronto, Ontario, Canada. The authors declare no conflicts of interest. Reprints: Karen A. Naert, MD, Clinical Fellow, Department of Laboratory Medicine and Pathobiology, University of Toronto and University Health Network, Toronto General Hospital, 200 Elizabeth Street, Room 11E-407, Toronto, Ontario M5G 2C4, Canada (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
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a mature adipocyte proliferation and infiltrative fibrosis. Other names include lipomatosis of nerve or neural fibrolipoma. FLH was first described in the literature by Mason5 in 1953. Since then, many case reports have been published describing these lesions in the median nerve, brachial plexus,6 cranial nerves,7 and plantar nerves8; however, the involvement of nuchal nerves has not been described.
CASE REPORT A healthy 25-year-old man presented with a 7-month history of an enlarging painless nodule at the base of the left anterior triangle of the neck. There were no associated neurologic or constitutional symptoms and no personal or family history of neurofibromatosis or neurologic disease. On physical examination, the lesion was approximately 1.0 cm, firm, mobile, and nontender. There were no neurologic deficits or skin changes. No imaging was performed. An excisional biopsy was performed, and a 1.0 · 0.7 · 0.5-cm lesion was removed. Grossly, it was white and nodular with the appearance of a lipoma. The specimen was fixed in 10% neutral buffered formalin and processed routinely for hematoxylin and eosin staining. Immunohistochemistry was performed to the following antibodies: SMA (Dako; dilution 1:100, dilution 1:6000), CD10 (Novocastra; dilution 1:40), CD68 (Dako; dilution 1:40), EMA (Ventana; standard dilution), CD56 (Ventana; standard dilution), PGP9.5 (Ventana; dilution 1:2), CD34 (Ventana; standard dilution), and beta-catenin (Dako; dilution 1:50).
RESULTS Light Microscopy Microscopically, the lesion was poorly circumscribed and focally infiltrated between skeletal muscle bundles (Fig. 1). The lesion was triphasic, composed of spindle cells, adipocytes, and neural tissue (Fig. 2). The spindle cells showed bland cytomorphology and were embedded in a dense fibrous stroma that had numerous admixed mature adipocytes and foci of myxoid change (Fig. 3). There was no nuclear hyperchromasia or mitotic activity, and lipoblasts were not identified. Numerous small nerves were also intimately admixed with the other components with a focal whorling or “pseudo-onion bulb” appearance of spindle cells around the nerves. Numerous intralesional mast cells were present.
Ancillary Studies Hale colloidal iron stain highlighted abundant mucin mixed throughout the stroma. CD56 highlighted the involved nerves. The spindle cell population was negative for SMA, Am J Dermatopathol Volume 37, Number 7, July 2015
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Am J Dermatopathol Volume 37, Number 7, July 2015
FIGURE 1. FLH showing classic histology with adipose tissue and bland spindle cells showing concentric whorling arrangements. The lesion surrounds skeletal muscle. Hematoxylin and eosin, ·10 magnification.
CD10, CD68, EMA, S100, PGP9.5, CD34, CD56, and betacatenin. Representative negative immunostains are shown in Figure 4. Based on the morphology and the negativity of the immunohistochemical markers, a diagnosis of FLH was made.
DISCUSSION FLH has been described in the literature as a benign fibrolipomatous lesion affecting peripheral nerves. Although
FIGURE 2. Triphasic histology with spindle cells, adipocytes, and nerve tissue. Hematoxylin and eosin, ·10 magnification. Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
An Unusual Soft Tissue Tumor of the Neck
median nerve involvement is relatively common, involvement of a nuchal nerve has never been described. Also, detailed immunohistochemical staining of this lesion has not been reported in the literature. The differential diagnosis of FLH is broad and includes benign and malignant lesions, including intraneural lipoma, neurofibroma, perineurioma, spindle cell lipoma, cellular neurothekeoma, traumatic neuroma, schwannoma, and liposarcoma. All these lesions share a relatively bland spindle cell population with varying amounts of the other components seen in FLH. The majority can be excluded based on the morphologic features alone, but immunohistochemistry can be helpful, particularly in light of the negativity that we have observed for all markers tested in FLH. If the adipocytic component is prominent, intraneural lipoma or spindle cell lipoma may enter the differential diagnosis. Intraneural lipoma shares with FLH a combination of mature adipocytes and neural tissue; however, there should be no significant spindle cell or fibrous component.9 Spindle cell lipoma shows considerable overlap with FLH, including a spindle cell proliferation with scattered adipocytes and the frequent occurrence of a myxoid stroma and the presence of mast cells. However, neural tissue is not seen in spindle cell lipoma, and the whorling appearance seen in FLH is not a prominent feature of spindle cell lipoma. Furthermore, spindle cell lipoma frequently shows “ropey” collagen, which is not characteristic of FLH. Spindle cell lipoma is positive for CD34,11 whereas FLH was negative for this marker in our case. Further study is required to determine whether CD34 is universally negative in FLH or if some cases may show CD34 positivity. The bland spindle cell population in a variably fibrous stroma, particularly in lesions with paucity of the adipocytic component, raises the differential diagnosis of entities, such as neurofibroma, perineurioma, schwannoma, and neurothekeoma. Like FLH, perineurioma consists of a spindle cell population that shows focal whorling; however, distinct nerves are not seen, and the lesional cells are positive for EMA, which we have shown to be negative in FLH.10 Perineuriomas also typically lack an adipocytic component, although a lipomatous variant has been reported.12,13 Neurofibromas share with FLH a bland spindle cell population and the presence of scattered mast cells; however, well-formed nerves are not seen. Adipocytes are typically entrapped rather than an intrinsic part of the neurofibroma, although sometimes they are seen within the lesion14–16 with Val-Bernal et al15 reporting intratumoral fat in 6.9% of neurofibromas in their large series. Schwannoma may also enter the differential diagnosis but typically shows distinct morphology, including Verocay bodies and Antoni A and B areas which allow it to be readily diagnosed. As for neurofibroma and perineurioma, fat is not a normal component of schwannoma but has been reported in some cases.16 Neurofibroma and schwannoma are of Schwannian origin and express S100,1 which is negative in FLH. Cellular neurothekeoma, a lesion of uncertain origin with variable morphology, may also show similar features to FLH, with spindle cells in a nested or plexiform pattern, often www.amjdermatopathology.com |
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Philp et al
FIGURE 3. Colloidal iron stain showing extensive mucin deposition.
with associated fibrous stroma and myxoid change. Epithelioid morphology, frequently observed in neurothekeoma, is absent in FLH. Immunohistochemistry may be of help in the distinction of this tumor from FLH, as neurothekeoma is positive for PGP9.5 and NKI/C3,17 and we have found PGP9.5 to be negative in our case of FLH. Caution is advised, as PGP9.5 is a nonspecific marker, and our observation of PGP9.5 negativity is based on a single case only. The combination of nerve tissue and fibrosis seen in FLH may suggest traumatic neuroma as a possible differential
Am J Dermatopathol Volume 37, Number 7, July 2015
diagnosis. Often, there is a clinical history of trauma in patients with traumatic neuroma. These lesions consist of disrupted small nerve twigs embedded in scar tissue. Although there may be some spindle cells around the nerve fibers, they are not as prominent as expected in FLH, and adipocytes would be incidentally entrapped rather than lesional. Although a malignant process would not be high on the differential diagnosis given the very bland morphology of FLH, well-differentiated or myxoid liposarcoma may occasionally be a consideration. In the case of welldifferentiated liposarcoma, the presence of focal hyperchromatic and atypical cells within the fibrous bands is helpful as is the presence of amplification of MDM2.18 Lipoblasts may be helpful if identified but are rarely seen in well-differentiated liposarcoma.18 Myxoid liposarcoma similarly may show a spindle cell component with variable adipocytic cells but has a characteristic chicken-wire vascular pattern and the t (12;16) (q13;p11) translocation.19 A summary of the differential diagnosis for FLH is provided in Table 1. Overall, histologic features that are useful in making the diagnosis of FLH include the intimate arrangement of the 3 component tissues: neural, adipocytic, and spindle cell and the overall bland cytology. Myxoid or mucinous changes and mast cells are also common. To our knowledge, a detailed immunohistochemical profile has not yet been reported for FLH. Here, we provide a first case with extensive immunohistochemical evaluation and demonstrate that the lesional spindle cells are negative for all tested antibodies. Immunohistochemical evaluation of additional cases would be required to confirm this profile; however, if it is universal in FLH, it would be of diagnostic assistance in
FIGURE 4. Representative immunohistochemical findings: (A) EMA, ·10 magnification; (B) S100, ·10 magnification; (C) PGP9.5, ·10 magnification; and (D) CD56, ·10 magnification.
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Am J Dermatopathol Volume 37, Number 7, July 2015
An Unusual Soft Tissue Tumor of the Neck
TABLE 1. Differential Diagnosis Lesion FLH
Intraneural lipoma Spindle cell lipoma
Neurofibroma Schwannoma
Perineurioma
Traumatic neuroma
Neurothekeoma
Well-differentiated liposarcoma Myxoid liposarcoma
Histologic Features
Useful Ancillary Studies
Triphasic: neural, adipose, and spindle cell components Whorling perineural appearance Myxoid/mucinous stroma Adipocytes and neural tissue No significant spindle cell proliferation Adipocytes and bland spindle cells Myxoid/mucinous stroma No neural component Wavy spindle cells Usually no adipocytic or distinct nerve component Spindle cells forming Verocay bodies and Antoni A and B areas Usually no adipocytic component Spindle cells forming whorled configurations Usually no adipocytic or well-formed nerve component Nerves with disrupted orientation embedded in fibrous scar tissue No prominent spindle cell component Spindle or epithelioid cells, usually larger than FLH
Negative for S100, EMA, CD34, CD10, SMA, and PGP9.5 Colloidal iron highlights intralesional mucin
No adipocytic component Predominantly adipocytes, some showing nuclear atypia Spindle cells and adipocytes in myxoid stroma Chicken-wire vascular pattern Lipoblasts
difficult cases because the entities entering the differential diagnosis usually have characteristic positive immunohistochemical results for certain stains. The imaging characteristics of FLH are unique, and magnetic resonance imaging (MRI) may be considered the gold standard for diagnosis.2 The lesion appears as a number of serpentine structures of low signal intensity that are seen on both T1- and T2-weighted images,20 which are representative of the thickened nerve fascicles. Other findings, including a coaxial cable-like appearance on axial imaging and spaghetti-like appearance on coronal imaging, are considered pathognomonic.21 These characteristic imaging findings along with clinical suspicion may therefore obviate the need for a biopsy, particularly when the lesion arises in classic locations like the median nerve. However, as FLH is a rare lesion, an MRI may not be ordered in all cases and a biopsy may be performed instead, as occurred in our case. Therefore, an awareness of the existence of this entity and its morphologic features and immunohistochemical profile are important to practicing pathologists. In conclusion, we report what, to our knowledge, is the first case of FLH arising in the neck. Although further study is required on additional cases to confirm the immunoprofile identified here, our case showed negativity for a myriad of immunohistochemical markers. This, coupled with the presence of abundant lesional mucin, may be a helpful Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
Not required CD34 positive
S100 positive S100 positive
EMA positive
Not required
Positive for PGP9.5 and NKI/C3; sometimes CD68, factor XIIIA, and SMA positive Characteristic cytogenetic findings (see text) Positive for CD34 Characteristic cytogenetic findings (see text)
feature in making the diagnosis and ruling out potential mimickers. REFERENCES 1. Kameh DS, Perez-Berenguer JL, Pearl GS. Lipofibromatous hamartoma and related peripheral nerve lesions. South Med J. 2000;93:800–802. 2. Ha JF, Teh BM, Abeysuriya DT, et al. Fibrolipomatous hamartoma of median nerve in the elbow: a case report. Ochsner J. 2012;12: 152–154. 3. Laurino L, Paolo Dei Tos A. Adipocytic tumors. In: Hornick J, ed Practical Soft Tissue Pathology: A Diagnostic Approach. Philadelphia, PA: Elsevier Saunders; 2013:296–297. 4. Silvermann T, Enzinger F. Fibrolipomatous hamartoma of nerve: a clinicopathologic analysis of 26 cases. Am J Surg Pathol. 1985;9:7–14. 5. Mason ML. Presentation of cases: Proceedings of the American Society of Surgery of the hand. J Bone Joint Surg Am. 1953;1:273–275. 6. Price AJ, Compson JP, Calonje E. Fibrolipomatous hamartoma of nerve arising in the brachial plexus. J Hand Surg Br. 1995;20:16–18. 7. Berti E, Roncaroli F. Fibrolipomatous hamartoma of a cranial nerve. Histopathology. 1994;24:391–392. 8. Hirakawa E, Miki H, Kobayashi S, et al. Lipofibromatous hamartoma of nerve in the foot. Acta Pathol Jpn. 1993;43:265–267. 9. Chiao HC, Marks KE, Bauer TW, et al. Intraneural lipoma of the sciatic nerve. Clin Orthop Relat Res. 1987;267–271. 10. Lee HY, Manasseh RG, Edis RH, et al. Intraneural perineurioma. J Clin Neurosci. 2009;12:1633–1636. 11. French CA, Mentzel T, Kutzner H, et al. Intradermal spindle cell/pleomorphic lipoma: a distinct subset. Am J Dermatopathol. 2000;22:496–502. 12. Zamecnik M. Perineurioma with adipocytes (lipomatous perineurioma). Am J Dermatopathol. 2003;25:171–173.
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13. Macarenco AC, Macarenco RS. Cutaneous lipomatous sclerosing perineurioma. Am J Dermatopathol. 2008;30:291–294. 14. Ahn SK, Ahn HJ, Kim TH, et al. Intratumoral fat in neurofibroma. Am J Dermatopathol. 2002;24:326–329. 15. Val-Bernal JF, Gonzalez-Vela MC. Cutaneous lipomatous neurofibroma: characterization and frequency. J Cutan Pathol. 2005;32: 274–279. 16. Plaza JA, Wakely PE Jr, Suster S. Lipoblastic nerve sheath tumors: report of a distinctive variant of neural soft tissue neoplasm with adipocytic differentiation. Am J Surg Pathol. 2006;30:337–344. 17. Husain S, Silver DN, Halperin AJ, et al. Histologic spectrum of neurothekeoma and the value of immunoperoxidase staining for S-100 protein
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18. 19. 20. 21.
in distinguishing it from melanoma. Am J Dermatopathol. 1994;16: 496–503. Sheth S, Dry S. Well-differentiated/dedifferentiated liposarcomas: a review with emphasis on recent molecular developments and targeted therapies. Pathol Case Rev. 2012;17:14–24. Orvieto E, Furlanetto A, Laurino L, et al. Myxoid and round cell liposarcoma: a spectrum of myxoid adipocytic neoplasia. Semin Diagn Pathol. 2001;18:267–273. Jain TP, Srivastava DN, Mittal R, et al. Fibrolipomatous hamartoma of median nerve. Australas Radiol. 2007;51:B98–B100. Marom EM, Helms CA. Fibrolipomatous hamartoma: pathognomonic on MR imaging. Skeletal Radiol. 1999;28:260–264.
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Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Fibrolipomatous Hamartoma of the Nerve Arising in the Neck: A Case Report With Review of the Literature and Differential Diagnosis Lauren Philp, MD,* Karen A. Naert, MD,† and Danny Ghazarian, MB ChB, PhD†
Abstract: We report an unusual case of a fibrolipomatous hamar-
toma that arose in a nuchal nerve. Typically, fibrolipomatous hamartoma, otherwise known as a neural fibrolipoma or lipomatosis of nerve, arises in the median nerve, brachial plexus, cranial nerves, or plantar nerves. The differential diagnosis is broad and includes benign and malignant spindle cell lesions, such as spindle cell lipoma, perineurioma, and myxoid liposarcoma. We were able to identify the lesion based on the typical histology, including triphasic composition with spindle cell, neural, and adipocytic components and whorled architecture. Because of the atypical location in the neck, detailed immunohistochemical staining was performed. The lesional spindle cells were negative for SMA, CD10, CD68, EMA, S100, PGP9.5, CD34, CD56, and beta-catenin. Colloidal iron stain highlighted marked intralesional mucin deposition. This detailed immunohistochemical profile is a useful diagnostic aid and to our knowledge has not been previously described. Key Words: fibrolipomatous hamartoma of nerve, neural fibrolipoma, lipomatosis of nerve (Am J Dermatopathol 2015;37:e78–e82)
INTRODUCTION Fibrolipomatous hamartoma of nerve (FLH) is a rare benign fibroproliferative condition affecting peripheral nerves. Although the exact pathogenesis remains unknown, it is speculated that FLH is a congenital lesion.1,2 Clinically it presents as a gradually expanding mass, most commonly occurring in the median nerve followed by the ulnar, radial, peroneal, and cranial nerves.3 This fibrofatty overgrowth generally presents in children and young adults and is frequently associated with macrodactyly.4 Other symptoms can include pain, paresthesias, and compression neuropathies. However, the most common clinical presentation is that of a soft, mobile, slowly expanding painless mass.1 Histologically, these lesions show a concentric epineural and perineural expansion with From the *Department of Plastic Surgery, University of Toronto, Toronto, Ontario, Canada; and †Department of Laboratory Medicine and Pathobiology, University of Toronto and University Health Network, Toronto, Ontario, Canada. The authors declare no conflicts of interest. Reprints: Karen A. Naert, MD, Clinical Fellow, Department of Laboratory Medicine and Pathobiology, University of Toronto and University Health Network, Toronto General Hospital, 200 Elizabeth Street, Room 11E-407, Toronto, Ontario M5G 2C4, Canada (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
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a mature adipocyte proliferation and infiltrative fibrosis. Other names include lipomatosis of nerve or neural fibrolipoma. FLH was first described in the literature by Mason5 in 1953. Since then, many case reports have been published describing these lesions in the median nerve, brachial plexus,6 cranial nerves,7 and plantar nerves8; however, the involvement of nuchal nerves has not been described.
CASE REPORT A healthy 25-year-old man presented with a 7-month history of an enlarging painless nodule at the base of the left anterior triangle of the neck. There were no associated neurologic or constitutional symptoms and no personal or family history of neurofibromatosis or neurologic disease. On physical examination, the lesion was approximately 1.0 cm, firm, mobile, and nontender. There were no neurologic deficits or skin changes. No imaging was performed. An excisional biopsy was performed, and a 1.0 · 0.7 · 0.5-cm lesion was removed. Grossly, it was white and nodular with the appearance of a lipoma. The specimen was fixed in 10% neutral buffered formalin and processed routinely for hematoxylin and eosin staining. Immunohistochemistry was performed to the following antibodies: SMA (Dako; dilution 1:100, dilution 1:6000), CD10 (Novocastra; dilution 1:40), CD68 (Dako; dilution 1:40), EMA (Ventana; standard dilution), CD56 (Ventana; standard dilution), PGP9.5 (Ventana; dilution 1:2), CD34 (Ventana; standard dilution), and beta-catenin (Dako; dilution 1:50).
RESULTS Light Microscopy Microscopically, the lesion was poorly circumscribed and focally infiltrated between skeletal muscle bundles (Fig. 1). The lesion was triphasic, composed of spindle cells, adipocytes, and neural tissue (Fig. 2). The spindle cells showed bland cytomorphology and were embedded in a dense fibrous stroma that had numerous admixed mature adipocytes and foci of myxoid change (Fig. 3). There was no nuclear hyperchromasia or mitotic activity, and lipoblasts were not identified. Numerous small nerves were also intimately admixed with the other components with a focal whorling or “pseudo-onion bulb” appearance of spindle cells around the nerves. Numerous intralesional mast cells were present.
Ancillary Studies Hale colloidal iron stain highlighted abundant mucin mixed throughout the stroma. CD56 highlighted the involved nerves. The spindle cell population was negative for SMA, Am J Dermatopathol Volume 37, Number 7, July 2015
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Am J Dermatopathol Volume 37, Number 7, July 2015
FIGURE 1. FLH showing classic histology with adipose tissue and bland spindle cells showing concentric whorling arrangements. The lesion surrounds skeletal muscle. Hematoxylin and eosin, ·10 magnification.
CD10, CD68, EMA, S100, PGP9.5, CD34, CD56, and betacatenin. Representative negative immunostains are shown in Figure 4. Based on the morphology and the negativity of the immunohistochemical markers, a diagnosis of FLH was made.
DISCUSSION FLH has been described in the literature as a benign fibrolipomatous lesion affecting peripheral nerves. Although
FIGURE 2. Triphasic histology with spindle cells, adipocytes, and nerve tissue. Hematoxylin and eosin, ·10 magnification. Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
An Unusual Soft Tissue Tumor of the Neck
median nerve involvement is relatively common, involvement of a nuchal nerve has never been described. Also, detailed immunohistochemical staining of this lesion has not been reported in the literature. The differential diagnosis of FLH is broad and includes benign and malignant lesions, including intraneural lipoma, neurofibroma, perineurioma, spindle cell lipoma, cellular neurothekeoma, traumatic neuroma, schwannoma, and liposarcoma. All these lesions share a relatively bland spindle cell population with varying amounts of the other components seen in FLH. The majority can be excluded based on the morphologic features alone, but immunohistochemistry can be helpful, particularly in light of the negativity that we have observed for all markers tested in FLH. If the adipocytic component is prominent, intraneural lipoma or spindle cell lipoma may enter the differential diagnosis. Intraneural lipoma shares with FLH a combination of mature adipocytes and neural tissue; however, there should be no significant spindle cell or fibrous component.9 Spindle cell lipoma shows considerable overlap with FLH, including a spindle cell proliferation with scattered adipocytes and the frequent occurrence of a myxoid stroma and the presence of mast cells. However, neural tissue is not seen in spindle cell lipoma, and the whorling appearance seen in FLH is not a prominent feature of spindle cell lipoma. Furthermore, spindle cell lipoma frequently shows “ropey” collagen, which is not characteristic of FLH. Spindle cell lipoma is positive for CD34,11 whereas FLH was negative for this marker in our case. Further study is required to determine whether CD34 is universally negative in FLH or if some cases may show CD34 positivity. The bland spindle cell population in a variably fibrous stroma, particularly in lesions with paucity of the adipocytic component, raises the differential diagnosis of entities, such as neurofibroma, perineurioma, schwannoma, and neurothekeoma. Like FLH, perineurioma consists of a spindle cell population that shows focal whorling; however, distinct nerves are not seen, and the lesional cells are positive for EMA, which we have shown to be negative in FLH.10 Perineuriomas also typically lack an adipocytic component, although a lipomatous variant has been reported.12,13 Neurofibromas share with FLH a bland spindle cell population and the presence of scattered mast cells; however, well-formed nerves are not seen. Adipocytes are typically entrapped rather than an intrinsic part of the neurofibroma, although sometimes they are seen within the lesion14–16 with Val-Bernal et al15 reporting intratumoral fat in 6.9% of neurofibromas in their large series. Schwannoma may also enter the differential diagnosis but typically shows distinct morphology, including Verocay bodies and Antoni A and B areas which allow it to be readily diagnosed. As for neurofibroma and perineurioma, fat is not a normal component of schwannoma but has been reported in some cases.16 Neurofibroma and schwannoma are of Schwannian origin and express S100,1 which is negative in FLH. Cellular neurothekeoma, a lesion of uncertain origin with variable morphology, may also show similar features to FLH, with spindle cells in a nested or plexiform pattern, often www.amjdermatopathology.com |
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Philp et al
FIGURE 3. Colloidal iron stain showing extensive mucin deposition.
with associated fibrous stroma and myxoid change. Epithelioid morphology, frequently observed in neurothekeoma, is absent in FLH. Immunohistochemistry may be of help in the distinction of this tumor from FLH, as neurothekeoma is positive for PGP9.5 and NKI/C3,17 and we have found PGP9.5 to be negative in our case of FLH. Caution is advised, as PGP9.5 is a nonspecific marker, and our observation of PGP9.5 negativity is based on a single case only. The combination of nerve tissue and fibrosis seen in FLH may suggest traumatic neuroma as a possible differential
Am J Dermatopathol Volume 37, Number 7, July 2015
diagnosis. Often, there is a clinical history of trauma in patients with traumatic neuroma. These lesions consist of disrupted small nerve twigs embedded in scar tissue. Although there may be some spindle cells around the nerve fibers, they are not as prominent as expected in FLH, and adipocytes would be incidentally entrapped rather than lesional. Although a malignant process would not be high on the differential diagnosis given the very bland morphology of FLH, well-differentiated or myxoid liposarcoma may occasionally be a consideration. In the case of welldifferentiated liposarcoma, the presence of focal hyperchromatic and atypical cells within the fibrous bands is helpful as is the presence of amplification of MDM2.18 Lipoblasts may be helpful if identified but are rarely seen in well-differentiated liposarcoma.18 Myxoid liposarcoma similarly may show a spindle cell component with variable adipocytic cells but has a characteristic chicken-wire vascular pattern and the t (12;16) (q13;p11) translocation.19 A summary of the differential diagnosis for FLH is provided in Table 1. Overall, histologic features that are useful in making the diagnosis of FLH include the intimate arrangement of the 3 component tissues: neural, adipocytic, and spindle cell and the overall bland cytology. Myxoid or mucinous changes and mast cells are also common. To our knowledge, a detailed immunohistochemical profile has not yet been reported for FLH. Here, we provide a first case with extensive immunohistochemical evaluation and demonstrate that the lesional spindle cells are negative for all tested antibodies. Immunohistochemical evaluation of additional cases would be required to confirm this profile; however, if it is universal in FLH, it would be of diagnostic assistance in
FIGURE 4. Representative immunohistochemical findings: (A) EMA, ·10 magnification; (B) S100, ·10 magnification; (C) PGP9.5, ·10 magnification; and (D) CD56, ·10 magnification.
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Am J Dermatopathol Volume 37, Number 7, July 2015
An Unusual Soft Tissue Tumor of the Neck
TABLE 1. Differential Diagnosis Lesion FLH
Intraneural lipoma Spindle cell lipoma
Neurofibroma Schwannoma
Perineurioma
Traumatic neuroma
Neurothekeoma
Well-differentiated liposarcoma Myxoid liposarcoma
Histologic Features
Useful Ancillary Studies
Triphasic: neural, adipose, and spindle cell components Whorling perineural appearance Myxoid/mucinous stroma Adipocytes and neural tissue No significant spindle cell proliferation Adipocytes and bland spindle cells Myxoid/mucinous stroma No neural component Wavy spindle cells Usually no adipocytic or distinct nerve component Spindle cells forming Verocay bodies and Antoni A and B areas Usually no adipocytic component Spindle cells forming whorled configurations Usually no adipocytic or well-formed nerve component Nerves with disrupted orientation embedded in fibrous scar tissue No prominent spindle cell component Spindle or epithelioid cells, usually larger than FLH
Negative for S100, EMA, CD34, CD10, SMA, and PGP9.5 Colloidal iron highlights intralesional mucin
No adipocytic component Predominantly adipocytes, some showing nuclear atypia Spindle cells and adipocytes in myxoid stroma Chicken-wire vascular pattern Lipoblasts
difficult cases because the entities entering the differential diagnosis usually have characteristic positive immunohistochemical results for certain stains. The imaging characteristics of FLH are unique, and magnetic resonance imaging (MRI) may be considered the gold standard for diagnosis.2 The lesion appears as a number of serpentine structures of low signal intensity that are seen on both T1- and T2-weighted images,20 which are representative of the thickened nerve fascicles. Other findings, including a coaxial cable-like appearance on axial imaging and spaghetti-like appearance on coronal imaging, are considered pathognomonic.21 These characteristic imaging findings along with clinical suspicion may therefore obviate the need for a biopsy, particularly when the lesion arises in classic locations like the median nerve. However, as FLH is a rare lesion, an MRI may not be ordered in all cases and a biopsy may be performed instead, as occurred in our case. Therefore, an awareness of the existence of this entity and its morphologic features and immunohistochemical profile are important to practicing pathologists. In conclusion, we report what, to our knowledge, is the first case of FLH arising in the neck. Although further study is required on additional cases to confirm the immunoprofile identified here, our case showed negativity for a myriad of immunohistochemical markers. This, coupled with the presence of abundant lesional mucin, may be a helpful Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
Not required CD34 positive
S100 positive S100 positive
EMA positive
Not required
Positive for PGP9.5 and NKI/C3; sometimes CD68, factor XIIIA, and SMA positive Characteristic cytogenetic findings (see text) Positive for CD34 Characteristic cytogenetic findings (see text)
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