578
Journal of the Royal Society of Medicine Volume 85 September 1992
Discussion Although rare, adrenal apoplexy has long been associated with heparin therapy'3, perhaps as a result of heparininduced thrombocytopenia24 which occurs in about 5% of heparin-treated patients6. The adrenal glands are usually supplied with three arteries which branch into many subdivisions, making infarction very unlikely. In contrast, they are drained by a single vein, and adrenal vein thrombosis has been implicated in adrenal apoplexy and may contribute to adrenal haemorrhage associated with heparin-induced thrombocytopenia4. Furthermore, experimental evidence suggests that it is the stressed adrenal gland, ie the ACTH-stimulated gland (as might be expected after major heart surgery), which is more susceptible to haemorrhage7. Our patient exhibited typical clinical findings associated with adrenal apoplexy, namely: abdominal pain radiating to the flank, vomiting, fever and a leucocytosis. In the context of heparin therapy, and particularly if the patient becomes thrombocytopenic, these findings should lead to a presumptive diagnosis of adrenal haemorrhage, which may be confirmed by computed tomography of the abdomen8'9. Although unilateral adrenal haemorrhage has been described10-12, bilateral haemorrhage is more common13, so that the CT scan findings in our patient of unilateral gland enlargement were presumably associated with occult damage to the other gland. The resultant hypoadrenalism may, as in this case, be diagnosed by a short Synacthen test, and should be treated immediately with appropriate steroid replacement.
2 Scully RE, Mark EJ, McNeely WF, McNeely BU. Case records of the Massachusetts General Hospital. N Engi J Med 1989;321:1595-603 3 Harper JR, Ginn WM, Taylor WJ. Bilateral adrenal hemorrhage - a complication of anticoagulant therapy. Am J-Med 1962;32:984-8 4 Findling JW, Korducki JM, Lahiri PK, Miller DD,. Raff H. Bilateral adrenal hemorrhage associated with heparin4nduced thrombocytopenia. Wisconsin Med J 1987;86:27-9 5 King DJ, Kelton JG. Heparin-associated thrombcytope cA Intern Med 1984;100:535-40 6 Clark OH, Hall AD, Schambelan M. Clinical manifestations of adrenal hemorrhage. Am J Surg 1974;128:219-24 7 Xarli VP, Steele AA, Davis PJ, Buescher ES, Rios Cn, Garcia; Bunuel R. Adrenal hemorrhage in the adult. Medicine 1978; 57:211-21 8 Liu L, Haskin ME, Rose LI, Bemis CE. Diagnosis of bilateral adrenocortical hemorrhage by computed tomography. Ann Intern Med 1982;97:720-1 9 Wheatley T, Gallagher S, Dixon AK. Adrenal insufficiency and bilateral adrenal enlargement: demonstration by computed tomography. Postgrad Med J 1985;61:435-8 10 Galin MA. Unilateral adrenal hemorrhage d4uring ACTHtherapy. N Engl J Med 195825:945-6 11 Miller A. Adrenal apoplexy. A report of two ca. Proc R Soc Med 1960;53:345-8 12 Castleman B, McNeely BU. Case records of the Mchusetts General Hospital. N Engi J Med 1969;280:772-6 13 Clark OH. Postoperative adrenal hemorrha. Ann- $g 1975;182:124-9
References 1 Amador E. Adrenal hemorrhage during anticoagulant therapy. A clinical and pathological study of ten cases. Ann Intern Med 1965;63:559-71
(Accepted 2 July 1991)
Granular cell tumour: an underdiagnosed cause of multifocal subcutaneous swellings
F Patel MB ChB MRCPath Department ofMorbid Anatomy and Histopathology, King's College Hospital, London Keywords: granular cell tumour; schwannoma; neurofibromatosis; multifocal subcutaneous swellings; clinical diagnosis
Granular cell tumours (GCT) are a recognized cause of multiple cutaneous swellings but the clinical diagnosis is rarely forthcoming. A preoperative diagnosis based on clinical grounds alone gives only 3% correct yield'. The diagnosis of malignancy is paradoxically not made histologically. This report of multifocal cutaneous GCT draws attention to the clinical dilemma in the management of the GCT and the need for an understanding of the condition. Case report An 18-year-old Afro-Caribbean male was referred with a slow growing swelling which had been present for at least 10 years on his buttock. He complained of discomfort on sitting. Correspondence to: Dr F Patel, Department of Forensic Medicine, Medical School, Guy's Hospital, London SE1 9RT
Figure 1. GCT. Low power view ofH&E sectiorn Note mitotic inactivity antd absence of cross striation
On examination the patient was a fit young man and had 12 other smaller identifiable cutaneous swellings which were non-tender. Some of the lesions had hyperpigmented skin. The lesions were smooth, firm and well circumscribed and appeared to be either intradermal or subcutaneous. There was no clinical evidence of visceral involvement. The specimen was 4.5x3.5x2.5 cm and showed a white soft tissue mass with a whorled cut surface. The histological sections showed large polygonal cells with strap-like forms in the dermis. The cytoplasm had characteristic eosinophilic coarse granules (Figure 1). The tumour was mitotically inactive and no cross-striation was visible. The granules together with larger eosinophilic cytoplasm bodies with halos stained positively with the PAS-diastase
0141-0768/92 090578-02/$02.00/0 © 1992 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 85 September 1992
klkk
-fi.
i.. ....:e...|
i 7" j
*ton pSiit favousqa nerv sheath'origin-
^strn postvt faor
a nerve
shath origi
preparation and for S-100 protein (Figure 2). Some of the small nerve bundles within the tumour were involved. A second lesion excised one month later had similar histopathological features.
Discussion GCT is a controversial lesion with many synonyms and an unresolved histogenesis4. It was originally thought to arise from muscle and known as 'granular cell myoblastoma'2. The term 'granular cell tumour' is desirable as the neoplastic nature of the lesion is uncertainiSAi. Most leading authors on this topic accept it as being of nerve sheath origin and prefer the nomenclature 'granular cell schwannoma' which incorporates the neuroectodermal derivation24. The ultrastructure and histochemical evidence, in particular staining for the S-100 protein support an origin from Schwann cells4"6. This neuroectodermal connection suggests that GCT may be similar to lesions seen in neurofibromatosis2'. There have been no accounts of GCT occurring in patients with von Recklinghausen's disease2. GCT is more common in the black population and multiple lesions are particularly frequent in this group7. Multiple lesions otherwise are uncommon' and familial cases are extremely rare8. The lesions occur in diverse anatomical sites24'7. GCT follows a benign clinical course although a malignant variant is known to occur rarely24. The symptoms will depend on the site and size of the lesion3 but are usually asymptomatic in the skin tissue. There may be tenderness suggesting neural involvement9.
Persistent diplopia following Streptococcus suis type 2 meningiti
J S MeechamMB ChB R C WorthMRcP Countess of Chester Hospital, Liverpool Road, Chester CHI 3ST Keywords: streptococcus suis type 2 meningitis; diplopia
Streptococcus suis type 2 meningitis is a zoonosis which is uncommon in the UK. It occurs in pig handlers and handlers of pig carcasses2. Previously documented sequelae include permanent deafness and vertigo;-this case was complicated by persistent diplopia.
579
The surgical differential diagnoses are numerous and an excisional biopsy is the only confirmatory diagnostic modality. GCT is usually diagnosed first at microscopy2. The histological confirmation in addition may demonstrate the clinically malignant variants. This is of paramount importance in the surgical management of these patients. The histological diagnosis of malignancy in GCT is, however, subjective', and may in fact not always be possible as similar morphology may be seen in the benign tumour"35. The diagnosis of malignancy is often based on the clinical behaviour of the lesion especially if there is metastatic spread, usually after several years2'3. GCT do not appear to regress spontaneously. Radiotherapy has no beneficial effect. When GCT is solitary, complete surgical excision with a rim ofperipheral tissue seems most appropriate and is effectively curative24. The recurrence rate (8%) is similar in lesions that are incompletely excised and suggests that a subsequent wider clearance is not necessary'. A clinical follow-up will enable symptomatic or rapidly growing lesions to be referred for local excision8'9. References 1 Lack EE, Worsham GF, Callihan MD, et aL Granular cell tumor: a clinicopathological study of 110 patients. J Surg Oncol 1980;13:301-16 2 Enzinger FM, Weis SW. Benign tumors and tumorlike lesions of uncertain histogenesis. In: Soft tissue tumor. St Louis: The CV Mosby company, 1983 3 Hajdu SI. Miscellaneous soft tissue tumors. In: Pathology ofsoft tissue tumors. Philadelphia: Lea & Febiger, 1979:510-35 4 Ashley DJ. Supporting tissues ofthe body - voluntary muscle. In: Evans' histological appearances oftumours, 3rd edn. Edinburgh: Churchill Livingstone, 1978:50-3 5 Buley ID, Gatter KC, Kelly PM,- et aL Granulosa cell tumours revisited. An immunohistological and ultrastructural study. Histopathology 1988;12:263-74 6 Armin A, Conelly EM, Rowden G. An immunoperoxidase investigation of S-100 protein in granular cell myoblastomas. Evidence of schwann cell derivation. Am J Clin Pathol 1983;
79:37-44 7 Vance 5, Hudson RP. Granular cell myoblastoma. Clinicopathological study of 42 patients. Am J Clin Pathol 1969; 52:208-11 8 Riflkin RH, Blocker SH, Palmer JO, Ternberg JL. Multiple granular cell tumors. A familial occurrence in children. Arch Surg 1986;121:945-7 9 White SW, Gallagher RL, Rodman OG. Multiple granular-cell tumors. J Dermatol Surg Oncol 1980;6:57-61
(Accepted 5 July 1991)
Case report A 46-year-old pig farmer was admitted having been unwell for 3 days. He described a sudden onset of clumsiness and vertigo, followed after 2 days by a severe frontal headache, high fever, confusion and vomiting. He owned approximately 200 pigs, all of which were healthy, and was not involved with their slaughter. There had been no recent travel abroad. Examination showed him to be disorientated, agitated, but afebrile; there were no rashes. nitially, there was no evidence of meningeal irritation, or focal neurological abnormality.- Within 2 h of admission, there had been a marked deterioration; he was pyrexal (39°C), and had obvious nuchaI rigidity with photophobia. After immediate treatment with 2.4 g intravenous benzyl penicillin and 1.0 g intravenous chloramphenicol,' a CT scan was performed to exclude a cerebral abscess. A lumbair puncture showed turbid cerebrinal fliid (CSF) underrad pre e, with a WBC of 10x10011 (95% polymorphs) and abundant gram-positive cocci. CSF protein was 4.5 gAl and glucose 0.6 mmol/l (plasma
0141-0768/92 090579-02/$02.00/0 X 1992 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 85 September 1992
Discussion Although rare, adrenal apoplexy has long been associated with heparin therapy'3, perhaps as a result of heparininduced thrombocytopenia24 which occurs in about 5% of heparin-treated patients6. The adrenal glands are usually supplied with three arteries which branch into many subdivisions, making infarction very unlikely. In contrast, they are drained by a single vein, and adrenal vein thrombosis has been implicated in adrenal apoplexy and may contribute to adrenal haemorrhage associated with heparin-induced thrombocytopenia4. Furthermore, experimental evidence suggests that it is the stressed adrenal gland, ie the ACTH-stimulated gland (as might be expected after major heart surgery), which is more susceptible to haemorrhage7. Our patient exhibited typical clinical findings associated with adrenal apoplexy, namely: abdominal pain radiating to the flank, vomiting, fever and a leucocytosis. In the context of heparin therapy, and particularly if the patient becomes thrombocytopenic, these findings should lead to a presumptive diagnosis of adrenal haemorrhage, which may be confirmed by computed tomography of the abdomen8'9. Although unilateral adrenal haemorrhage has been described10-12, bilateral haemorrhage is more common13, so that the CT scan findings in our patient of unilateral gland enlargement were presumably associated with occult damage to the other gland. The resultant hypoadrenalism may, as in this case, be diagnosed by a short Synacthen test, and should be treated immediately with appropriate steroid replacement.
2 Scully RE, Mark EJ, McNeely WF, McNeely BU. Case records of the Massachusetts General Hospital. N Engi J Med 1989;321:1595-603 3 Harper JR, Ginn WM, Taylor WJ. Bilateral adrenal hemorrhage - a complication of anticoagulant therapy. Am J-Med 1962;32:984-8 4 Findling JW, Korducki JM, Lahiri PK, Miller DD,. Raff H. Bilateral adrenal hemorrhage associated with heparin4nduced thrombocytopenia. Wisconsin Med J 1987;86:27-9 5 King DJ, Kelton JG. Heparin-associated thrombcytope cA Intern Med 1984;100:535-40 6 Clark OH, Hall AD, Schambelan M. Clinical manifestations of adrenal hemorrhage. Am J Surg 1974;128:219-24 7 Xarli VP, Steele AA, Davis PJ, Buescher ES, Rios Cn, Garcia; Bunuel R. Adrenal hemorrhage in the adult. Medicine 1978; 57:211-21 8 Liu L, Haskin ME, Rose LI, Bemis CE. Diagnosis of bilateral adrenocortical hemorrhage by computed tomography. Ann Intern Med 1982;97:720-1 9 Wheatley T, Gallagher S, Dixon AK. Adrenal insufficiency and bilateral adrenal enlargement: demonstration by computed tomography. Postgrad Med J 1985;61:435-8 10 Galin MA. Unilateral adrenal hemorrhage d4uring ACTHtherapy. N Engl J Med 195825:945-6 11 Miller A. Adrenal apoplexy. A report of two ca. Proc R Soc Med 1960;53:345-8 12 Castleman B, McNeely BU. Case records of the Mchusetts General Hospital. N Engi J Med 1969;280:772-6 13 Clark OH. Postoperative adrenal hemorrha. Ann- $g 1975;182:124-9
References 1 Amador E. Adrenal hemorrhage during anticoagulant therapy. A clinical and pathological study of ten cases. Ann Intern Med 1965;63:559-71
(Accepted 2 July 1991)
Granular cell tumour: an underdiagnosed cause of multifocal subcutaneous swellings
F Patel MB ChB MRCPath Department ofMorbid Anatomy and Histopathology, King's College Hospital, London Keywords: granular cell tumour; schwannoma; neurofibromatosis; multifocal subcutaneous swellings; clinical diagnosis
Granular cell tumours (GCT) are a recognized cause of multiple cutaneous swellings but the clinical diagnosis is rarely forthcoming. A preoperative diagnosis based on clinical grounds alone gives only 3% correct yield'. The diagnosis of malignancy is paradoxically not made histologically. This report of multifocal cutaneous GCT draws attention to the clinical dilemma in the management of the GCT and the need for an understanding of the condition. Case report An 18-year-old Afro-Caribbean male was referred with a slow growing swelling which had been present for at least 10 years on his buttock. He complained of discomfort on sitting. Correspondence to: Dr F Patel, Department of Forensic Medicine, Medical School, Guy's Hospital, London SE1 9RT
Figure 1. GCT. Low power view ofH&E sectiorn Note mitotic inactivity antd absence of cross striation
On examination the patient was a fit young man and had 12 other smaller identifiable cutaneous swellings which were non-tender. Some of the lesions had hyperpigmented skin. The lesions were smooth, firm and well circumscribed and appeared to be either intradermal or subcutaneous. There was no clinical evidence of visceral involvement. The specimen was 4.5x3.5x2.5 cm and showed a white soft tissue mass with a whorled cut surface. The histological sections showed large polygonal cells with strap-like forms in the dermis. The cytoplasm had characteristic eosinophilic coarse granules (Figure 1). The tumour was mitotically inactive and no cross-striation was visible. The granules together with larger eosinophilic cytoplasm bodies with halos stained positively with the PAS-diastase
0141-0768/92 090578-02/$02.00/0 © 1992 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 85 September 1992
klkk
-fi.
i.. ....:e...|
i 7" j
*ton pSiit favousqa nerv sheath'origin-
^strn postvt faor
a nerve
shath origi
preparation and for S-100 protein (Figure 2). Some of the small nerve bundles within the tumour were involved. A second lesion excised one month later had similar histopathological features.
Discussion GCT is a controversial lesion with many synonyms and an unresolved histogenesis4. It was originally thought to arise from muscle and known as 'granular cell myoblastoma'2. The term 'granular cell tumour' is desirable as the neoplastic nature of the lesion is uncertainiSAi. Most leading authors on this topic accept it as being of nerve sheath origin and prefer the nomenclature 'granular cell schwannoma' which incorporates the neuroectodermal derivation24. The ultrastructure and histochemical evidence, in particular staining for the S-100 protein support an origin from Schwann cells4"6. This neuroectodermal connection suggests that GCT may be similar to lesions seen in neurofibromatosis2'. There have been no accounts of GCT occurring in patients with von Recklinghausen's disease2. GCT is more common in the black population and multiple lesions are particularly frequent in this group7. Multiple lesions otherwise are uncommon' and familial cases are extremely rare8. The lesions occur in diverse anatomical sites24'7. GCT follows a benign clinical course although a malignant variant is known to occur rarely24. The symptoms will depend on the site and size of the lesion3 but are usually asymptomatic in the skin tissue. There may be tenderness suggesting neural involvement9.
Persistent diplopia following Streptococcus suis type 2 meningiti
J S MeechamMB ChB R C WorthMRcP Countess of Chester Hospital, Liverpool Road, Chester CHI 3ST Keywords: streptococcus suis type 2 meningitis; diplopia
Streptococcus suis type 2 meningitis is a zoonosis which is uncommon in the UK. It occurs in pig handlers and handlers of pig carcasses2. Previously documented sequelae include permanent deafness and vertigo;-this case was complicated by persistent diplopia.
579
The surgical differential diagnoses are numerous and an excisional biopsy is the only confirmatory diagnostic modality. GCT is usually diagnosed first at microscopy2. The histological confirmation in addition may demonstrate the clinically malignant variants. This is of paramount importance in the surgical management of these patients. The histological diagnosis of malignancy in GCT is, however, subjective', and may in fact not always be possible as similar morphology may be seen in the benign tumour"35. The diagnosis of malignancy is often based on the clinical behaviour of the lesion especially if there is metastatic spread, usually after several years2'3. GCT do not appear to regress spontaneously. Radiotherapy has no beneficial effect. When GCT is solitary, complete surgical excision with a rim ofperipheral tissue seems most appropriate and is effectively curative24. The recurrence rate (8%) is similar in lesions that are incompletely excised and suggests that a subsequent wider clearance is not necessary'. A clinical follow-up will enable symptomatic or rapidly growing lesions to be referred for local excision8'9. References 1 Lack EE, Worsham GF, Callihan MD, et aL Granular cell tumor: a clinicopathological study of 110 patients. J Surg Oncol 1980;13:301-16 2 Enzinger FM, Weis SW. Benign tumors and tumorlike lesions of uncertain histogenesis. In: Soft tissue tumor. St Louis: The CV Mosby company, 1983 3 Hajdu SI. Miscellaneous soft tissue tumors. In: Pathology ofsoft tissue tumors. Philadelphia: Lea & Febiger, 1979:510-35 4 Ashley DJ. Supporting tissues ofthe body - voluntary muscle. In: Evans' histological appearances oftumours, 3rd edn. Edinburgh: Churchill Livingstone, 1978:50-3 5 Buley ID, Gatter KC, Kelly PM,- et aL Granulosa cell tumours revisited. An immunohistological and ultrastructural study. Histopathology 1988;12:263-74 6 Armin A, Conelly EM, Rowden G. An immunoperoxidase investigation of S-100 protein in granular cell myoblastomas. Evidence of schwann cell derivation. Am J Clin Pathol 1983;
79:37-44 7 Vance 5, Hudson RP. Granular cell myoblastoma. Clinicopathological study of 42 patients. Am J Clin Pathol 1969; 52:208-11 8 Riflkin RH, Blocker SH, Palmer JO, Ternberg JL. Multiple granular cell tumors. A familial occurrence in children. Arch Surg 1986;121:945-7 9 White SW, Gallagher RL, Rodman OG. Multiple granular-cell tumors. J Dermatol Surg Oncol 1980;6:57-61
(Accepted 5 July 1991)
Case report A 46-year-old pig farmer was admitted having been unwell for 3 days. He described a sudden onset of clumsiness and vertigo, followed after 2 days by a severe frontal headache, high fever, confusion and vomiting. He owned approximately 200 pigs, all of which were healthy, and was not involved with their slaughter. There had been no recent travel abroad. Examination showed him to be disorientated, agitated, but afebrile; there were no rashes. nitially, there was no evidence of meningeal irritation, or focal neurological abnormality.- Within 2 h of admission, there had been a marked deterioration; he was pyrexal (39°C), and had obvious nuchaI rigidity with photophobia. After immediate treatment with 2.4 g intravenous benzyl penicillin and 1.0 g intravenous chloramphenicol,' a CT scan was performed to exclude a cerebral abscess. A lumbair puncture showed turbid cerebrinal fliid (CSF) underrad pre e, with a WBC of 10x10011 (95% polymorphs) and abundant gram-positive cocci. CSF protein was 4.5 gAl and glucose 0.6 mmol/l (plasma
0141-0768/92 090579-02/$02.00/0 X 1992 The Royal Society of Medicine
