EXTRAORDINARY CASE REPORT
Congenital Granular Cell Tumor of the Arm: A Rare Presentation Asli Aksu Çerman, MD,* Damlanur Sakiz, MD,† Sezgi Sarikaya Solak, MD,* Ilknur Kivanç Altunay, MD,* and Özben Yalçin, MD†
Abstract: Congenital granular cell tumors are uncommon benign tumors of newborns that mainly affect oral mucosa, especially the maxillary alveolar ridge. They are predominantly seen in female newborns, and cutaneous involvement is extremely rare. In this report, we present a case of congenital granular cell tumor on the arm of one of the male monozygotic twins and discuss the differential diagnosis of granular cell phenotype. Key Word: congenital granular cell tumor (Am J Dermatopathol 2015;37:712–714)
INTRODUCTION Congenital granular cell tumor (CGCT) is a rare benign tumor that is present at birth. The case was first described by Neumann in 1871.1 The tumor is usually found in the alveolar ridges of neonates.2,3 The etiology and histogenesis is unknown. Granular cell cytoplasmic change is an unusual morphologic feature that may also lead to diagnostic confusion. We report an unusual occurrence of CGCT on the arm of one of the male monozygotic twins.
CASE REPORT A 1-day-old preterm male infant was born by cesarean section after an uncomplicated monozygotic twin pregnancy. He was referred to the dermatology clinic for evaluation of lesions on his left arm, which were present at birth. The dermatological examination revealed 4 small, flat yellowish plaques measuring 1 to 3 cm in size on the extensor surface of his left arm (Figs. 1A, B). No other pathological skin or mucocutaneous lesion was found. There was no associated abnormality in the antenatal history of his mother. His identical twin brother was healthy and he did not have any abnormal skin finding on examination. A 3-mm punch biopsy was performed for the differential diagnosis of juvenile xanthogranuloma and connective tissue nevi. The histopathological examination of the lesions showed diffuse infiltration of the dermis that was composed of large cells containing abundant granular cytoplasm with small, uniform round nuclei (Fig. 2A). The granules were periodic acid-Schiff–positive, and immunostaining for CD68 and vimentin was positive (Figs. 2B, C). The cells were nonreactive for S100, CD34, neuron-specific enolase From the Departments of *Dermatology, and †Pathology, S¸is¸li Etfal Training and Research Hospital, Istanbul, Turkey. The authors declare no conflicts of interest. Reprints: Asli Aksu Çerman, MD, Department of Dermatology, S¸is¸li Etfal Training and Research Hospital, Halaskargazi Cad., Etfal S., S¸is¸li, Istanbul 34371, Turkey (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
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| www.amjdermatopathology.com
(NSE), desmin, CD31, myoglobulin, PGP9,5, calretinin A, and keratins. Based on these findings, a diagnosis of CGCT was made. The patient was lost to follow-up later.
DISCUSSION CGCTs are uncommon benign tumors of newborns. They mainly affect the oral mucosa, especially the alveolar ridge, and are described as “congenital epulis.” This condition has a remarkable female preponderance, and 10% of patients have multiple tumors.2,3 The main differential diagnosis for CGCT is adult granular cell tumor (GCT). Early onset, the absence of pseudoepitheliomatous hyperplasia of the overlying squamous epithelium, and no nerve bundles make CGCT different from GCT.2 Although histologically, the granular cells in both forms are indistinguishable, one significant difference is that the cells in the acquired form typically stain positive for S100.2–4 In the literature, in CGCT cases, positive vimentin immunoreactivity has been most frequently reported (93% of the cases), followed by NSE (48% of the cases).3 Although CGCT is able to regress spontaneously, without recurrence, even after incomplete excision, GCT has no tendency toward spontaneous regression and may recur postresection.2–4 In our case, the lesion was negative for S100 and positive for vimentin, confirming that it was CGCT. The pathogenesis of these 2 lesions is still uncertain. It is widely accepted that GCT originates from peripheral nerve Schwann cells. However, it has also been hypothesized that CGCT originates from the degenerative processes affecting mesenchymal stem cells.3,4 The granular cell change is not specific for any particular cell type. Rather, this phenotype is related to increased lysosome content within cell cytoplasm. CD68 is a lysosome-associated glycoprotein, and increased immunoreactivity to it demonstrates the increased autophagocytic activity in our case.3,5 Granular changes because of the accumulation of lysosomes can be observed in a variety of neoplasms, including leiomyoma, leiomyosarcoma, dermatofibroma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, benign melanocytic lesion, melanoma, fibrous papule, angiosarcoma, basal cell carcinoma, metastatic tumors, and primitive nonneural GCTs (so-called primitive polypoid GCTs).5–11 Primitive polypoid GCT was first described by LeBoit et al6 in 1991. Subsequently, Lazar and Fletcher7 reported a series of similar tumors that they named “primitive nonneural granular cell tumor.” In contrast to our patient, this neoplasm is characterized by Am J Dermatopathol Volume 37, Number 9, September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 9, September 2015
FIGURE 1. A, CGCT. B, Yellowish, small flat plaques on the extensor surface of the left arm.
a cutaneous location typically in the papillary dermis, a polypoid configuration, an epidermal collarette, nuclear atypia, and numerous mitoses.5 The tumor cells do not stain for S100 protein and for other epithelial, melanocytic, and myoid markers. Positive reactivity is seen with CD68, NKI/C3, NSE, and factor XIIIa.7,8 The histomorphological appearance and absence of actin, desmin, and/or caldesmon immunoreactivity effectively exclude leiomyoma and leiomyosarcoma.8,9 Basal cell carcinomas with granular cell change are usually of the nodular type with an immunohistochemical profile demonstrating reactivity with cytokeratins.10 Granular cell atypical fibroxanthoma usually presents as a rapidly enlarging
Congenital Granular Cell Tumor of the Arm
dome-shaped nodule and typically located on sun-exposed areas of elderly patients. Histologically, it is characterized by spindle or polygonal cells containing foamy cytoplasm, nuclear polymorphism, and frequent mitotic figures.7,9 Dermatofibromas typically display epidermal hyperplasia, hyperpigmentation of the basal layer, multinucleate giant cells, and collagen sclerosis. Spindle-shaped cells are distributed between collagen bundles.11 Melanoma or a benign melanocytic lesion can demonstrate a junctional component or some nesting of cells and would have immunoreactivity for S100 protein.7–9 The granular cell variant of fibrous papule is restricted to the central face and is less cellular than other variants, containing only focal wispy histiocytes.12 Cutaneous involvement in CGCT, as in our patient, is extremely rare, and to the best of our knowledge, only 2 cases have been reported in the literature. One of them is a 1-day-old newborn girl, presenting with flesh-colored to slightly orange papules on her left arm.4 The second case was described by Chang et al,13 a congenital granular cell dendrocytosis in a boy presenting with numerous, pale flat papules located on the face and extremities. Compared with our case in these 2 cases, the CD34 was positive. Surgical excision is curative, and no recurrence even after incomplete excision has been reported in CGCT.2,3 It may regress spontaneously, and a malignant transformation has never been reported.2 Although frequent monitoring for regression may be used as a management option, conservative excision is the traditional treatment modality.2–4 In conclusion, CGCT’s clinical appearance may be variable, and it may be difficult to distinguish it from other diseases. Because histopathology is the gold standard in the diagnostic process, it is essential to perform it when there is a clinical suspicion of CGCT. It is important for dermatologists and dermatopathologists to be aware of the varying entities that may exhibit granular cell changes. The differential diagnosis may initially be broad, but careful evaluation of clinical, histological, and immunohistochemical findings should enable a precise diagnosis to be rendered.
FIGURE 2. A, Diffuse infiltration of the dermis that is composed of large cells containing abundant granular cytoplasm and small, uniform round nuclei (hematoxylin and eosin stain, original magnification, ·200). B, Positive immunostaining for CD68 (original magnification, ·400). C, Positive immunostaining for vimentin (original magnification, ·400). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.amjdermatopathology.com |
713
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 9, September 2015
Çerman et al
REFERENCES 1. Neumann E. Ein fall von kongenitaler epulis. Arch Heilkd. 1871;12: 189–190. 2. Conrad R, Perez MC. Congenital granular cell epulis. Arch Pathol Lab Med. 2014;138:128–131. 3. Vered M, Dobriyan A, Buchner A. Congenital granular cell epulis presents an immunohistochemical profile that distinguishes it from the granular cell tumor of the adult. Virchows Arch. 2009;454:303–310. 4. Zaenglein AL, Meehan SA, Orlow SJ. Congenital granular cell tumors localized to the arm. Pediatr Dermatol. 2001;18:234–237. 5. Schoedel KE, Bastacky S, Silverman A. An S-100 negative granular cell tumor with malignant potential: report of a case. J Am Acad Dermatol. 1998;39:894–898. 6. LeBoit PE, Barr RJ, Burall S, et al. Primitive polypoid granular-cell tumor and other cutaneous granular-cell neoplasms of apparent nonneural origin. Am J Surg Pathol. 1991;15:48–58.
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| www.amjdermatopathology.com
7. Lazar AJ, Fletcher CD. Primitive nonneural granular cell tumors of skin. Am J Surg Pathol. 2005;29:927–934. 8. Yeh I, Tran DT, Davis TL, et al. An infiltrative variant of nonneural granular cell tumor: a case report. J Cutan Pathol. 2009;36: 46–51. 9. Wright NA, Thomas CG, Calame A, et al. Granular cell atypical fibroxanthoma: case report and review of the literature. J Cutan Pathol. 2010;37:380–385. 10. Jedrych J, Busam KJ. Multiple lesions of granular cell basal cell carcinoma: a case report. J Cutan Pathol. 2014;41:45–50. 11. Soyer PH, Metze D, Kerl H. Granular cell dermatofibroma. Am J Dermatopathol. 1997;19:168–173. 12. Jacyk WK, Rütten A, Requena L. Fibrous papule of the face with granular cells. Dermatology. 2008;216:56–59. 13. Chang SE, Choi JH, Sung KJ, et al. Congenital CD34-positive granular cell dendrocytosis. J Cutan Pathol. 1999;26:253–258.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Congenital Granular Cell Tumor of the Arm: A Rare Presentation Asli Aksu Çerman, MD,* Damlanur Sakiz, MD,† Sezgi Sarikaya Solak, MD,* Ilknur Kivanç Altunay, MD,* and Özben Yalçin, MD†
Abstract: Congenital granular cell tumors are uncommon benign tumors of newborns that mainly affect oral mucosa, especially the maxillary alveolar ridge. They are predominantly seen in female newborns, and cutaneous involvement is extremely rare. In this report, we present a case of congenital granular cell tumor on the arm of one of the male monozygotic twins and discuss the differential diagnosis of granular cell phenotype. Key Word: congenital granular cell tumor (Am J Dermatopathol 2015;37:712–714)
INTRODUCTION Congenital granular cell tumor (CGCT) is a rare benign tumor that is present at birth. The case was first described by Neumann in 1871.1 The tumor is usually found in the alveolar ridges of neonates.2,3 The etiology and histogenesis is unknown. Granular cell cytoplasmic change is an unusual morphologic feature that may also lead to diagnostic confusion. We report an unusual occurrence of CGCT on the arm of one of the male monozygotic twins.
CASE REPORT A 1-day-old preterm male infant was born by cesarean section after an uncomplicated monozygotic twin pregnancy. He was referred to the dermatology clinic for evaluation of lesions on his left arm, which were present at birth. The dermatological examination revealed 4 small, flat yellowish plaques measuring 1 to 3 cm in size on the extensor surface of his left arm (Figs. 1A, B). No other pathological skin or mucocutaneous lesion was found. There was no associated abnormality in the antenatal history of his mother. His identical twin brother was healthy and he did not have any abnormal skin finding on examination. A 3-mm punch biopsy was performed for the differential diagnosis of juvenile xanthogranuloma and connective tissue nevi. The histopathological examination of the lesions showed diffuse infiltration of the dermis that was composed of large cells containing abundant granular cytoplasm with small, uniform round nuclei (Fig. 2A). The granules were periodic acid-Schiff–positive, and immunostaining for CD68 and vimentin was positive (Figs. 2B, C). The cells were nonreactive for S100, CD34, neuron-specific enolase From the Departments of *Dermatology, and †Pathology, S¸is¸li Etfal Training and Research Hospital, Istanbul, Turkey. The authors declare no conflicts of interest. Reprints: Asli Aksu Çerman, MD, Department of Dermatology, S¸is¸li Etfal Training and Research Hospital, Halaskargazi Cad., Etfal S., S¸is¸li, Istanbul 34371, Turkey (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
712
| www.amjdermatopathology.com
(NSE), desmin, CD31, myoglobulin, PGP9,5, calretinin A, and keratins. Based on these findings, a diagnosis of CGCT was made. The patient was lost to follow-up later.
DISCUSSION CGCTs are uncommon benign tumors of newborns. They mainly affect the oral mucosa, especially the alveolar ridge, and are described as “congenital epulis.” This condition has a remarkable female preponderance, and 10% of patients have multiple tumors.2,3 The main differential diagnosis for CGCT is adult granular cell tumor (GCT). Early onset, the absence of pseudoepitheliomatous hyperplasia of the overlying squamous epithelium, and no nerve bundles make CGCT different from GCT.2 Although histologically, the granular cells in both forms are indistinguishable, one significant difference is that the cells in the acquired form typically stain positive for S100.2–4 In the literature, in CGCT cases, positive vimentin immunoreactivity has been most frequently reported (93% of the cases), followed by NSE (48% of the cases).3 Although CGCT is able to regress spontaneously, without recurrence, even after incomplete excision, GCT has no tendency toward spontaneous regression and may recur postresection.2–4 In our case, the lesion was negative for S100 and positive for vimentin, confirming that it was CGCT. The pathogenesis of these 2 lesions is still uncertain. It is widely accepted that GCT originates from peripheral nerve Schwann cells. However, it has also been hypothesized that CGCT originates from the degenerative processes affecting mesenchymal stem cells.3,4 The granular cell change is not specific for any particular cell type. Rather, this phenotype is related to increased lysosome content within cell cytoplasm. CD68 is a lysosome-associated glycoprotein, and increased immunoreactivity to it demonstrates the increased autophagocytic activity in our case.3,5 Granular changes because of the accumulation of lysosomes can be observed in a variety of neoplasms, including leiomyoma, leiomyosarcoma, dermatofibroma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, benign melanocytic lesion, melanoma, fibrous papule, angiosarcoma, basal cell carcinoma, metastatic tumors, and primitive nonneural GCTs (so-called primitive polypoid GCTs).5–11 Primitive polypoid GCT was first described by LeBoit et al6 in 1991. Subsequently, Lazar and Fletcher7 reported a series of similar tumors that they named “primitive nonneural granular cell tumor.” In contrast to our patient, this neoplasm is characterized by Am J Dermatopathol Volume 37, Number 9, September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 9, September 2015
FIGURE 1. A, CGCT. B, Yellowish, small flat plaques on the extensor surface of the left arm.
a cutaneous location typically in the papillary dermis, a polypoid configuration, an epidermal collarette, nuclear atypia, and numerous mitoses.5 The tumor cells do not stain for S100 protein and for other epithelial, melanocytic, and myoid markers. Positive reactivity is seen with CD68, NKI/C3, NSE, and factor XIIIa.7,8 The histomorphological appearance and absence of actin, desmin, and/or caldesmon immunoreactivity effectively exclude leiomyoma and leiomyosarcoma.8,9 Basal cell carcinomas with granular cell change are usually of the nodular type with an immunohistochemical profile demonstrating reactivity with cytokeratins.10 Granular cell atypical fibroxanthoma usually presents as a rapidly enlarging
Congenital Granular Cell Tumor of the Arm
dome-shaped nodule and typically located on sun-exposed areas of elderly patients. Histologically, it is characterized by spindle or polygonal cells containing foamy cytoplasm, nuclear polymorphism, and frequent mitotic figures.7,9 Dermatofibromas typically display epidermal hyperplasia, hyperpigmentation of the basal layer, multinucleate giant cells, and collagen sclerosis. Spindle-shaped cells are distributed between collagen bundles.11 Melanoma or a benign melanocytic lesion can demonstrate a junctional component or some nesting of cells and would have immunoreactivity for S100 protein.7–9 The granular cell variant of fibrous papule is restricted to the central face and is less cellular than other variants, containing only focal wispy histiocytes.12 Cutaneous involvement in CGCT, as in our patient, is extremely rare, and to the best of our knowledge, only 2 cases have been reported in the literature. One of them is a 1-day-old newborn girl, presenting with flesh-colored to slightly orange papules on her left arm.4 The second case was described by Chang et al,13 a congenital granular cell dendrocytosis in a boy presenting with numerous, pale flat papules located on the face and extremities. Compared with our case in these 2 cases, the CD34 was positive. Surgical excision is curative, and no recurrence even after incomplete excision has been reported in CGCT.2,3 It may regress spontaneously, and a malignant transformation has never been reported.2 Although frequent monitoring for regression may be used as a management option, conservative excision is the traditional treatment modality.2–4 In conclusion, CGCT’s clinical appearance may be variable, and it may be difficult to distinguish it from other diseases. Because histopathology is the gold standard in the diagnostic process, it is essential to perform it when there is a clinical suspicion of CGCT. It is important for dermatologists and dermatopathologists to be aware of the varying entities that may exhibit granular cell changes. The differential diagnosis may initially be broad, but careful evaluation of clinical, histological, and immunohistochemical findings should enable a precise diagnosis to be rendered.
FIGURE 2. A, Diffuse infiltration of the dermis that is composed of large cells containing abundant granular cytoplasm and small, uniform round nuclei (hematoxylin and eosin stain, original magnification, ·200). B, Positive immunostaining for CD68 (original magnification, ·400). C, Positive immunostaining for vimentin (original magnification, ·400). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.amjdermatopathology.com |
713
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 9, September 2015
Çerman et al
REFERENCES 1. Neumann E. Ein fall von kongenitaler epulis. Arch Heilkd. 1871;12: 189–190. 2. Conrad R, Perez MC. Congenital granular cell epulis. Arch Pathol Lab Med. 2014;138:128–131. 3. Vered M, Dobriyan A, Buchner A. Congenital granular cell epulis presents an immunohistochemical profile that distinguishes it from the granular cell tumor of the adult. Virchows Arch. 2009;454:303–310. 4. Zaenglein AL, Meehan SA, Orlow SJ. Congenital granular cell tumors localized to the arm. Pediatr Dermatol. 2001;18:234–237. 5. Schoedel KE, Bastacky S, Silverman A. An S-100 negative granular cell tumor with malignant potential: report of a case. J Am Acad Dermatol. 1998;39:894–898. 6. LeBoit PE, Barr RJ, Burall S, et al. Primitive polypoid granular-cell tumor and other cutaneous granular-cell neoplasms of apparent nonneural origin. Am J Surg Pathol. 1991;15:48–58.
714
| www.amjdermatopathology.com
7. Lazar AJ, Fletcher CD. Primitive nonneural granular cell tumors of skin. Am J Surg Pathol. 2005;29:927–934. 8. Yeh I, Tran DT, Davis TL, et al. An infiltrative variant of nonneural granular cell tumor: a case report. J Cutan Pathol. 2009;36: 46–51. 9. Wright NA, Thomas CG, Calame A, et al. Granular cell atypical fibroxanthoma: case report and review of the literature. J Cutan Pathol. 2010;37:380–385. 10. Jedrych J, Busam KJ. Multiple lesions of granular cell basal cell carcinoma: a case report. J Cutan Pathol. 2014;41:45–50. 11. Soyer PH, Metze D, Kerl H. Granular cell dermatofibroma. Am J Dermatopathol. 1997;19:168–173. 12. Jacyk WK, Rütten A, Requena L. Fibrous papule of the face with granular cells. Dermatology. 2008;216:56–59. 13. Chang SE, Choi JH, Sung KJ, et al. Congenital CD34-positive granular cell dendrocytosis. J Cutan Pathol. 1999;26:253–258.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
