revue neurologique 170 (2014) 228–234
A. Bougea * E. Anagnostou E. Stamboulis E. Kararizou Department of Neurology, Athens National University, Aiginition Hospital, Vass. Sofias Ave. 72–74, 11528 Athens, Greece *Corresponding author. E-mail addresses: [email protected], [email protected] (A. Bougea) Received 15 October Received in revised form 27 October Accepted 20 November Available online 18 March
2013 2013 2013 2014
0035-3787/$ – see front matter # 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neurol.2013.11.004
Paraneoplastic dermatomyositis with glycogen accumulation in muscle Dermatomyosite parane´oplasique avec accumulation de glycoge`ne dans le muscle
A 60-year-old woman presented facial erythema exacerbated by sun exposure. One month later, she complained of diffuse
229
myalgia and arthralgia with moderate weakness, and a diagnosis of dermatomyositis was considered. Routine laboratory tests were normal, but creatine kinase level was increased (12,168 units/L; normal value 140 units/L). Needle electromyography showed myogenic patterns predominantly in girdle muscles. Body scan, upper gastrointestinal endoscopy and colonoscopy were normal. Prednisone therapy was introduced (60 mg per day), and deltoid muscle biopsy was performed 10 days after onset of corticotherapy. Paraffin sections showed variation in muscle fiber size, but neither necrosis nor inflammatory infiltrates. On frozen sections, a peripheral vacuolar appearance was consistent with glycogen accumulation in some muscle fibers. Histochemical reactions showed normal distribution of muscle fiber types, but myophosphorylase activity was deficient. Immunohistochemistry detected major histocompatibility complex class I antigen positivity on muscle fibers. Electron microscopy showed an accumulation of free glycogen in muscle fiber cytoplasm and tuboloreticular inclusions in endothelial cells (Fig. 1). One year later, the patient presented with a red-purple facial rash, eyelid swelling, and cutaneous ulceration over the index. Mobilization of wrists and finger joints was painful. She had some difficulties raising the arms and getting up from sitting, and complained of breath shortness. Chest X-ray showed a moderate bilateral pleural effusion and cardiac evaluation was in favor of a cardiomyopathy. Molecular analysis of myophosphorylase (PYGM) gene showed no sequence variations for type V glycogenosis. Biochemical studies showed moderate muscle glycogen elevation, decreased glycogenolysis and glycolysis, and reduced myophosphorylase activity. A second body scan
Fig. 1 – (A) Haematoxylin and eosin stained frozen section showing sub-sarcolemmal vacuoles in muscle fibers (at a higher magnification in inset) (scale = 100 mm). (B) Periodic acid-Schiff staining showing glycogen-filled vacuoles within muscle fibers (scale = 50 mm). Inset corresponds to myophosphorylase staining showing the complete loss of enzyme expression. (C) Immunostaining demonstrating expression of major histocompatibility complex class I antigens on muscle fibers (scale = 100 mm). (D) Electron microscopy showing a tubuloreticular inclusion in the cytoplasm of an endothelial cell (scale = 1 mm).
230
revue neurologique 170 (2014) 228–234
was performed which evidenced an ovarian tumor with liver metastasis, and the patient died a few months later. Our patient fulfilled clinico-pathological criteria for dermatomyositis [1]. Absence of inflammatory cells could be related to corticotherapy which had been introduced before muscle biopsy. Age, debilitating skin disease and cardiomyopathy suggested paraneoplastic dermatomyositis and an ovarian cancer was discovered, the most common underlying malignancy associated with dermatomyositis in women. However, glycogen accumulation and histochemical absence of myophosphorylase activity in muscle justified to consider an associated type V glycogenosis, inasmuch as Mc Ardle’s disease can mimic a refractory dermatomyositis. This was emphasized in a previous report concerning a 25-year-old woman who complained of recurrent muscle weakness and was diagnosed with a dermatomyositis on the presence of bilateral skin lesions on both arms. A first muscle biopsy showed intense inflammatory infiltrates, but a second biopsy showed a myophosphorylase deficiency, characteristic of Mc Ardle’s disease confirmed by R49X and W79R mutations in the PYGM gene [2]. On the other hand, and similarly to our observation, a case of juvenile dermatomyositis confirmed by muscle biopsy revealed an atypical perifascicular glycogen accumulation [3]. The mechanism for glycogen overload in such inflammatory conditions remains to be determined, but from exercise testing and muscle biopsy in a woman with dermatomyositis, it was demonstrated that an inflammatory mechanism interfered with myophosphorylase activity and muscle aerobic function, with a normalization of the responses of serum lactate and pyruvate after corticosteroid therapy [4]. Such interference possibly occurred in our patient, and glycogen accumulation confounded diagnosis.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
references
[1] Dubowitz V, Sewry CA. Muscle biopsy. A practical approach. Third edition, London: Saunders Elsevier; 2007. [2] Gomez-Cerezo JF, Pagan Munoz B, Gutierrez M, Alfageme M, Morales C, Barbado FJ, McArdle’s disease presented as refractory dermatomyositis, Eur J. Intern Med 2008;19:e20–2. [3] Sampson JB, Chin SS, Clayton FC, Pestronk A, Swoboda KJ, Flanigan KM. An unusual pathologic feature associated with dermatomyositis. Neuromuscul Disord 2006;16:391–3. [4] Kunishige M, Mitsui T, Endo I, Matsumoto T. Dermatomyositis associated with impairment in both muscle aerobic and anaerobic function. Clin Neuropathol 2005;24:32–5.
A. Lagueny M.L. Martin-Negrier A. Bredin Service de pathologie, universite´ Bordeaux, hoˆpital Pellegrin, place Ame´lie-Raba-Le´on, 33076 Bordeaux cedex, France
J.L. Berge-Lefranc Hoˆpital de la Conception, 147, boulevard Baille, 13385 Marseille cedex 5, France M. Piraud Hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron cedex, France A. Vital* Service de pathologie, universite´ Bordeaux, hoˆpital Pellegrin, place Ame´lie-Raba-Le´on, 33076 Bordeaux cedex, France *Corresponding author. E-mail address: [email protected] (M.L. Martin-Negrier) Received 16 July Received in revised form 12 September Accepted 13 September Available online 6 March
2013 2013 2013 2014
0035-3787/$ – see front matter # 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neurol.2013.09.009
Intramedullary metastasis of a cutaneous squamous cell carcinoma Me´tastase intrame´dullaire d’un carcinome cutane´ e´pidermoı¨de
A 69-year-old patient with nasal cutaneous squamous cell carcinoma (CSCC) presented with progressive right leg monoplegia. Clinical examination revealed Brown-Se´quard syndrome with a loss of motor function, proprioception and fine touch in her right leg and a loss of pain and temperature sensation in her left leg and a C3 sensory level. Spinal cord MRI showed an intramedullary lesion from the D1 to D3 level with gadolinium enhancement and a spinal cord edema (Fig. 1). Pathologic examination after stereotaxic biopsy confirmed CSCC metastasis (Fig. 2). The patient received corticosteroids (1 mg per kg per day), which moderately improved the neurological symptoms, and radiation therapy was proposed. CSCC metastases are rare, and high-risk CSCC can spread along nerves, fascial or bony planes and via lymphatics. Distant metastasis can affect the lungs, liver, bones, other cutaneous sites and, in extremely rare cases, the central nervous system [1,2]. Intramedullary metastasis of CSCC has never been reported.
A. Bougea * E. Anagnostou E. Stamboulis E. Kararizou Department of Neurology, Athens National University, Aiginition Hospital, Vass. Sofias Ave. 72–74, 11528 Athens, Greece *Corresponding author. E-mail addresses: [email protected], [email protected] (A. Bougea) Received 15 October Received in revised form 27 October Accepted 20 November Available online 18 March
2013 2013 2013 2014
0035-3787/$ – see front matter # 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neurol.2013.11.004
Paraneoplastic dermatomyositis with glycogen accumulation in muscle Dermatomyosite parane´oplasique avec accumulation de glycoge`ne dans le muscle
A 60-year-old woman presented facial erythema exacerbated by sun exposure. One month later, she complained of diffuse
229
myalgia and arthralgia with moderate weakness, and a diagnosis of dermatomyositis was considered. Routine laboratory tests were normal, but creatine kinase level was increased (12,168 units/L; normal value 140 units/L). Needle electromyography showed myogenic patterns predominantly in girdle muscles. Body scan, upper gastrointestinal endoscopy and colonoscopy were normal. Prednisone therapy was introduced (60 mg per day), and deltoid muscle biopsy was performed 10 days after onset of corticotherapy. Paraffin sections showed variation in muscle fiber size, but neither necrosis nor inflammatory infiltrates. On frozen sections, a peripheral vacuolar appearance was consistent with glycogen accumulation in some muscle fibers. Histochemical reactions showed normal distribution of muscle fiber types, but myophosphorylase activity was deficient. Immunohistochemistry detected major histocompatibility complex class I antigen positivity on muscle fibers. Electron microscopy showed an accumulation of free glycogen in muscle fiber cytoplasm and tuboloreticular inclusions in endothelial cells (Fig. 1). One year later, the patient presented with a red-purple facial rash, eyelid swelling, and cutaneous ulceration over the index. Mobilization of wrists and finger joints was painful. She had some difficulties raising the arms and getting up from sitting, and complained of breath shortness. Chest X-ray showed a moderate bilateral pleural effusion and cardiac evaluation was in favor of a cardiomyopathy. Molecular analysis of myophosphorylase (PYGM) gene showed no sequence variations for type V glycogenosis. Biochemical studies showed moderate muscle glycogen elevation, decreased glycogenolysis and glycolysis, and reduced myophosphorylase activity. A second body scan
Fig. 1 – (A) Haematoxylin and eosin stained frozen section showing sub-sarcolemmal vacuoles in muscle fibers (at a higher magnification in inset) (scale = 100 mm). (B) Periodic acid-Schiff staining showing glycogen-filled vacuoles within muscle fibers (scale = 50 mm). Inset corresponds to myophosphorylase staining showing the complete loss of enzyme expression. (C) Immunostaining demonstrating expression of major histocompatibility complex class I antigens on muscle fibers (scale = 100 mm). (D) Electron microscopy showing a tubuloreticular inclusion in the cytoplasm of an endothelial cell (scale = 1 mm).
230
revue neurologique 170 (2014) 228–234
was performed which evidenced an ovarian tumor with liver metastasis, and the patient died a few months later. Our patient fulfilled clinico-pathological criteria for dermatomyositis [1]. Absence of inflammatory cells could be related to corticotherapy which had been introduced before muscle biopsy. Age, debilitating skin disease and cardiomyopathy suggested paraneoplastic dermatomyositis and an ovarian cancer was discovered, the most common underlying malignancy associated with dermatomyositis in women. However, glycogen accumulation and histochemical absence of myophosphorylase activity in muscle justified to consider an associated type V glycogenosis, inasmuch as Mc Ardle’s disease can mimic a refractory dermatomyositis. This was emphasized in a previous report concerning a 25-year-old woman who complained of recurrent muscle weakness and was diagnosed with a dermatomyositis on the presence of bilateral skin lesions on both arms. A first muscle biopsy showed intense inflammatory infiltrates, but a second biopsy showed a myophosphorylase deficiency, characteristic of Mc Ardle’s disease confirmed by R49X and W79R mutations in the PYGM gene [2]. On the other hand, and similarly to our observation, a case of juvenile dermatomyositis confirmed by muscle biopsy revealed an atypical perifascicular glycogen accumulation [3]. The mechanism for glycogen overload in such inflammatory conditions remains to be determined, but from exercise testing and muscle biopsy in a woman with dermatomyositis, it was demonstrated that an inflammatory mechanism interfered with myophosphorylase activity and muscle aerobic function, with a normalization of the responses of serum lactate and pyruvate after corticosteroid therapy [4]. Such interference possibly occurred in our patient, and glycogen accumulation confounded diagnosis.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
references
[1] Dubowitz V, Sewry CA. Muscle biopsy. A practical approach. Third edition, London: Saunders Elsevier; 2007. [2] Gomez-Cerezo JF, Pagan Munoz B, Gutierrez M, Alfageme M, Morales C, Barbado FJ, McArdle’s disease presented as refractory dermatomyositis, Eur J. Intern Med 2008;19:e20–2. [3] Sampson JB, Chin SS, Clayton FC, Pestronk A, Swoboda KJ, Flanigan KM. An unusual pathologic feature associated with dermatomyositis. Neuromuscul Disord 2006;16:391–3. [4] Kunishige M, Mitsui T, Endo I, Matsumoto T. Dermatomyositis associated with impairment in both muscle aerobic and anaerobic function. Clin Neuropathol 2005;24:32–5.
A. Lagueny M.L. Martin-Negrier A. Bredin Service de pathologie, universite´ Bordeaux, hoˆpital Pellegrin, place Ame´lie-Raba-Le´on, 33076 Bordeaux cedex, France
J.L. Berge-Lefranc Hoˆpital de la Conception, 147, boulevard Baille, 13385 Marseille cedex 5, France M. Piraud Hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron cedex, France A. Vital* Service de pathologie, universite´ Bordeaux, hoˆpital Pellegrin, place Ame´lie-Raba-Le´on, 33076 Bordeaux cedex, France *Corresponding author. E-mail address: [email protected] (M.L. Martin-Negrier) Received 16 July Received in revised form 12 September Accepted 13 September Available online 6 March
2013 2013 2013 2014
0035-3787/$ – see front matter # 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.neurol.2013.09.009
Intramedullary metastasis of a cutaneous squamous cell carcinoma Me´tastase intrame´dullaire d’un carcinome cutane´ e´pidermoı¨de
A 69-year-old patient with nasal cutaneous squamous cell carcinoma (CSCC) presented with progressive right leg monoplegia. Clinical examination revealed Brown-Se´quard syndrome with a loss of motor function, proprioception and fine touch in her right leg and a loss of pain and temperature sensation in her left leg and a C3 sensory level. Spinal cord MRI showed an intramedullary lesion from the D1 to D3 level with gadolinium enhancement and a spinal cord edema (Fig. 1). Pathologic examination after stereotaxic biopsy confirmed CSCC metastasis (Fig. 2). The patient received corticosteroids (1 mg per kg per day), which moderately improved the neurological symptoms, and radiation therapy was proposed. CSCC metastases are rare, and high-risk CSCC can spread along nerves, fascial or bony planes and via lymphatics. Distant metastasis can affect the lungs, liver, bones, other cutaneous sites and, in extremely rare cases, the central nervous system [1,2]. Intramedullary metastasis of CSCC has never been reported.
