380
Pathology (2015), 47(4), June
CORRESPONDENCE
Malignant inflammatory myofibroblastic tumour of the uterus Sir, Inflammatory myofibroblastic tumour (IMT) is a distinctive mesenchymal neoplasm characterised by a spindle cell proliferation with admixed lymphocytes, plasma cells and/or eosinophils.1 It occurs mainly in children and young adults in the lungs or soft tissue, but may arise from many sites over a wide age range. Uterine IMT is rare. Previous reports have stressed its good prognosis, with a complete absence of recurrences or metastases.2,3 However, we have recently encountered a case which metastasised and led to the death of the patient. Our case was of a 72-year-old woman who presented with post-menopausal vaginal bleeding. The patient presented with a history of mild pelvic pain and 2 weeks of post-menopausal spotting. She had a known fibroid uterus for the previous decade but this was noted to be enlarging on recent ultrasound. She had no history of unexplained weight loss and no fever. Blood results at diagnosis revealed a normal haemoglobin, platelet count and white cell count. Gamma globulins and other inflammatory markers were not tested. On examination, she had an enlarged uterus and two vaginal masses. One vaginal mass was biopsied. Following a diagnosis of malignancy, she had a total abdominal hysterectomy, bilateral salpingo-oophorectomy and excision of the vaginal masses. Macroscopic examination showed that the uterus was distorted by a single 105 100 95 mm ovoid mass within the anterior wall of the myometrium. The cut surface showed a well demarcated tumour with extensive haemorrhagic necrosis and jelly-like mucoid material seeping through the cut surface (Fig. 1). The anterior vaginal mass was 23 mm in diameter and the posterior was 10 mm and both were composed of similar mucoid material. Microscopic examination of the uterine and vaginal masses showed a spindle cell tumour with marked tumour cell necrosis and haemorrhage (Fig.?2A). The tumour cells formed fascicles of spindle cells with eosinophilic cytoplasm, marked nuclear atypia and a mitotic rate of 10 per 10 high power fields. The spindle cells were separated by a myxoid background with admixed lymphocytes and plasma cells (Fig.?2B). Immunohistochemistry showed the spindle cells were diffusely strongly
A
B
C Fig. 2 (A) Spindle cell tumour with tumour cell necrosis. (B) Atypical spindle cells, admixed lymphocytes and myxoid stroma (H&E). (C) ALK 1 positive in nuclei and cytoplasm (immunoperoxidase).
Fig. 1 Uterus showing a large necrotic haemorrhagic myometrial tumour.
positive for ALK 1 in nuclei and cytoplasm, diffusely strongly positive for CD10, and rarely positive for desmin; smooth muscle actin, calponin, Myo-D1, myogenin, S100, CAM 5.2, CD21, CD35, Epstein–Barr virus (EBV) and Herpes hominis virus type 8 (HHV8) were negative (Fig.?2C). The cervix, endometrium, uterine serosa, fallopian tubes and ovaries were?unremarkable. FISH testing was performed using the Vysis ALK breakapart probe located at chromosome 2p23. A total of 250 tumour cells were analysed and a normal signal pattern, indicated by the presence of two fusion signals, was observed in all tumour cells. There was no evidence of either additional signals indicating
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
copy number change for ALK 1, or, a separation of the ALK 1 fusion signal demonstrating a rearrangement of the ALK 1 gene. Despite the negative fluorescence in situ hybridisation (FISH), a diagnosis of IMT was made on the routine histology of a myxoid spindle cell tumour with admixed lymphocytes and plasma cells, supported by the positive ALK 1. ALK 1 immunohistochemical stain positivity, although supportive of the diagnosis of IMT, is not entirely specific as positivity has been detected in leiomyosarcomas, rhabdomyosarcomas, malignant peripheral nerve sheath tumour, malignant fibrous histiocytoma, primitive neuroectodermal tumour (PNET) and Ewing’s sarcoma.4 In our case, the lack of routine histological or immunohistochemical differentiation towards one of these tumours and presence of admixed inflammatory cells favoured IMT over these other diagnoses. Cytokeratin positivity has been reported in 89–24% of IMT, but was negative in our case.5,6 Positive dendritic cell markers such as CD21 and CD35 have been reported in IMT and indicate a similar abnormality of chromosome 2p23 as ALK 1, but these markers were negative in our case.4 Viral markers of follicular dendritic cell tumour, i.e., EBV and HHV8, were also negative. Post-operatively the patient developed pulmonary emboli. When recovered, she received pelvic radiotherapy. Five months later, she developed a large anterior vaginal recurrence which extended almost to the introitus, a second mass at the vaginal vault and third lesion posterior to the vault. A CT scan showed pulmonary metastases. The patient elected not to have chemotherapy and died of progressive disease 20 months after diagnosis. What is the best nomenclature for our case? Coffin and Fletcher in the WHO ‘blue book’ use the non-committal term ‘tumour’ to describe IMT as they state that, while IMT has a 25% recurrence rate and 2% metastatic rate, histological criteria cannot be used as a guide to prognosis.1 Contrary to the WHO, our case was clearly malignant histologically and clinically, so a diagnosis of IMT with its relatively good prognosis is misleading. Montgomery et al. get around this predicament by using the term ‘malignant IMT’ for their unusual bladder tumour which appeared 4 years post-irradiation for prostate cancer, and although it had ALK rearrangement, immunohistochemical staining for ALK was negative.7 Our case is also best described as a ‘malignant IMT’. The question arises whether IMT encompasses two different tumours, depending on age and site. The usual type of IMT occurs in the lungs and soft tissue of children and young adults and has a generally good, but occasionally unpredictable course. Another form may arise in the viscera of middle-aged to elderly adults where malignancy is more predictable on histological criteria. Supporting the two tumour types hypothesis, ALK 1 gene fusion is uncommon in IMT diagnosed in adults >40 years, yet is seen in about half of IMT overall.5 It may also help to explain the overlap between IMT and smooth muscle tumours in mature adults as both may be ALK 1 positive on immunohistochemistry. Li et al. found ALK 1 positive in three of 18 (17%) cases of LMS. Further studies are needed to clarify the nature of this adult form of IMT.8 In conclusion, we report a malignant IMT in a 72-year-old female who died of this unusual tumour previously reported to have a good outcome in the uterus. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose.
381
Gabriella Ak1 Kenneth Jaaback2 Hui Yin3 Paul Maley4 James Scurry3 1
Pathology Department, Port Moresby General Hospital, Port Moresby, Papua and New Guinea; 2Hunter Centre for Gynaecological Cancer, John Hunter Hospital, New Lambton Heights, 3Division of Anatomical Pathology, Pathology North, Hunter New England, John Hunter Hospital, New Lambton Heights and Faculty of Health Sciences, University of Newcastle, Callaghan, and 4 Molecular Cytogenetics, Department of Molecular Medicine, Pathology North, Hunter New England, John Hunter Hospital, New Lambton Heights, NSW, Australia Contact A/Prof James Scurry. E-mail: [email protected] 1. Coffin CM, Fletcher JA. Inflammatory myofibroblastic tumour. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon: IARC Press, 2013; 83–4. 2. Rabban JT, Zaloudek CJ, Shekitka KM, Tavassoli FA. Inflammatory myofibroblastictumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. Am J Surg Pathol 2005; 29: 1348–55. 3. Shintaku M, Fukushima A. Inflammatory myofibroblastictumor of the uterus with prominent myxoid change. Pathol Int 2006; 56: 625–8. 4. Cessna MH, Zhou H, Sanger WG, et al. Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases. Mod Pathol 2002; 15: 931–8. 5. Freeman A, Geddes N, Munson P, et al. Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature. Mod Pathol 2004; 17: 765–71. 6. Sukov WR, Cheville JC, Carlson AW, et al. Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastictumor from malignant spindle cell lesions of the urinary bladder. Mod Pathol 2007; 20: 592–603. 7. Montgomery EA, Shuster DD, Burkart AL, et al. Inflammatory myofibroblastictumors of the urinary tract: a clinicopathologic study of 46 cases, including a malignant example inflammatory fibrosarcoma and a subset associated with high-grade urothelial carcinoma. Am J Surg Pathol 2006; 30: 1502–12. 8. Li XQ, Hisaoka M, Shi DR, Zhu XZ, Hashimoto H. Expression of anaplastic lymphoma kinase in soft tissue tumors: an immunohistochemical and molecular study of 249 cases. Hum Pathol 2004; 35: 711–21.
DOI: 10.1097/PAT.0000000000000260
Tophaceous gout in the pelvis Sir, Gout is the clinical manifestation of hyperuricaemia and is characterised by the deposition of monosodium urate crystals in soft tissues, which invokes an inflammatory response.1 Hyperuricaemia occurs when there is an imbalance between uric acid production and excretion. For more than 90% of patients the primary problem is reduced renal excretion of uric acid.2 Gout usually presents acutely and intermittently as pain and swelling in and around joints of the distal extremities because uric acid precipitates first in relatively avascular, low temperature environments.3 Uncommonly, gout first presents in its chronic form as tophaceous gout, with no history of an acute intermittent stage.3–5 Rarely, tophaceous gout develops in deep soft
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
Pathology (2015), 47(4), June
CORRESPONDENCE
Malignant inflammatory myofibroblastic tumour of the uterus Sir, Inflammatory myofibroblastic tumour (IMT) is a distinctive mesenchymal neoplasm characterised by a spindle cell proliferation with admixed lymphocytes, plasma cells and/or eosinophils.1 It occurs mainly in children and young adults in the lungs or soft tissue, but may arise from many sites over a wide age range. Uterine IMT is rare. Previous reports have stressed its good prognosis, with a complete absence of recurrences or metastases.2,3 However, we have recently encountered a case which metastasised and led to the death of the patient. Our case was of a 72-year-old woman who presented with post-menopausal vaginal bleeding. The patient presented with a history of mild pelvic pain and 2 weeks of post-menopausal spotting. She had a known fibroid uterus for the previous decade but this was noted to be enlarging on recent ultrasound. She had no history of unexplained weight loss and no fever. Blood results at diagnosis revealed a normal haemoglobin, platelet count and white cell count. Gamma globulins and other inflammatory markers were not tested. On examination, she had an enlarged uterus and two vaginal masses. One vaginal mass was biopsied. Following a diagnosis of malignancy, she had a total abdominal hysterectomy, bilateral salpingo-oophorectomy and excision of the vaginal masses. Macroscopic examination showed that the uterus was distorted by a single 105 100 95 mm ovoid mass within the anterior wall of the myometrium. The cut surface showed a well demarcated tumour with extensive haemorrhagic necrosis and jelly-like mucoid material seeping through the cut surface (Fig. 1). The anterior vaginal mass was 23 mm in diameter and the posterior was 10 mm and both were composed of similar mucoid material. Microscopic examination of the uterine and vaginal masses showed a spindle cell tumour with marked tumour cell necrosis and haemorrhage (Fig.?2A). The tumour cells formed fascicles of spindle cells with eosinophilic cytoplasm, marked nuclear atypia and a mitotic rate of 10 per 10 high power fields. The spindle cells were separated by a myxoid background with admixed lymphocytes and plasma cells (Fig.?2B). Immunohistochemistry showed the spindle cells were diffusely strongly
A
B
C Fig. 2 (A) Spindle cell tumour with tumour cell necrosis. (B) Atypical spindle cells, admixed lymphocytes and myxoid stroma (H&E). (C) ALK 1 positive in nuclei and cytoplasm (immunoperoxidase).
Fig. 1 Uterus showing a large necrotic haemorrhagic myometrial tumour.
positive for ALK 1 in nuclei and cytoplasm, diffusely strongly positive for CD10, and rarely positive for desmin; smooth muscle actin, calponin, Myo-D1, myogenin, S100, CAM 5.2, CD21, CD35, Epstein–Barr virus (EBV) and Herpes hominis virus type 8 (HHV8) were negative (Fig.?2C). The cervix, endometrium, uterine serosa, fallopian tubes and ovaries were?unremarkable. FISH testing was performed using the Vysis ALK breakapart probe located at chromosome 2p23. A total of 250 tumour cells were analysed and a normal signal pattern, indicated by the presence of two fusion signals, was observed in all tumour cells. There was no evidence of either additional signals indicating
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
CORRESPONDENCE
copy number change for ALK 1, or, a separation of the ALK 1 fusion signal demonstrating a rearrangement of the ALK 1 gene. Despite the negative fluorescence in situ hybridisation (FISH), a diagnosis of IMT was made on the routine histology of a myxoid spindle cell tumour with admixed lymphocytes and plasma cells, supported by the positive ALK 1. ALK 1 immunohistochemical stain positivity, although supportive of the diagnosis of IMT, is not entirely specific as positivity has been detected in leiomyosarcomas, rhabdomyosarcomas, malignant peripheral nerve sheath tumour, malignant fibrous histiocytoma, primitive neuroectodermal tumour (PNET) and Ewing’s sarcoma.4 In our case, the lack of routine histological or immunohistochemical differentiation towards one of these tumours and presence of admixed inflammatory cells favoured IMT over these other diagnoses. Cytokeratin positivity has been reported in 89–24% of IMT, but was negative in our case.5,6 Positive dendritic cell markers such as CD21 and CD35 have been reported in IMT and indicate a similar abnormality of chromosome 2p23 as ALK 1, but these markers were negative in our case.4 Viral markers of follicular dendritic cell tumour, i.e., EBV and HHV8, were also negative. Post-operatively the patient developed pulmonary emboli. When recovered, she received pelvic radiotherapy. Five months later, she developed a large anterior vaginal recurrence which extended almost to the introitus, a second mass at the vaginal vault and third lesion posterior to the vault. A CT scan showed pulmonary metastases. The patient elected not to have chemotherapy and died of progressive disease 20 months after diagnosis. What is the best nomenclature for our case? Coffin and Fletcher in the WHO ‘blue book’ use the non-committal term ‘tumour’ to describe IMT as they state that, while IMT has a 25% recurrence rate and 2% metastatic rate, histological criteria cannot be used as a guide to prognosis.1 Contrary to the WHO, our case was clearly malignant histologically and clinically, so a diagnosis of IMT with its relatively good prognosis is misleading. Montgomery et al. get around this predicament by using the term ‘malignant IMT’ for their unusual bladder tumour which appeared 4 years post-irradiation for prostate cancer, and although it had ALK rearrangement, immunohistochemical staining for ALK was negative.7 Our case is also best described as a ‘malignant IMT’. The question arises whether IMT encompasses two different tumours, depending on age and site. The usual type of IMT occurs in the lungs and soft tissue of children and young adults and has a generally good, but occasionally unpredictable course. Another form may arise in the viscera of middle-aged to elderly adults where malignancy is more predictable on histological criteria. Supporting the two tumour types hypothesis, ALK 1 gene fusion is uncommon in IMT diagnosed in adults >40 years, yet is seen in about half of IMT overall.5 It may also help to explain the overlap between IMT and smooth muscle tumours in mature adults as both may be ALK 1 positive on immunohistochemistry. Li et al. found ALK 1 positive in three of 18 (17%) cases of LMS. Further studies are needed to clarify the nature of this adult form of IMT.8 In conclusion, we report a malignant IMT in a 72-year-old female who died of this unusual tumour previously reported to have a good outcome in the uterus. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose.
381
Gabriella Ak1 Kenneth Jaaback2 Hui Yin3 Paul Maley4 James Scurry3 1
Pathology Department, Port Moresby General Hospital, Port Moresby, Papua and New Guinea; 2Hunter Centre for Gynaecological Cancer, John Hunter Hospital, New Lambton Heights, 3Division of Anatomical Pathology, Pathology North, Hunter New England, John Hunter Hospital, New Lambton Heights and Faculty of Health Sciences, University of Newcastle, Callaghan, and 4 Molecular Cytogenetics, Department of Molecular Medicine, Pathology North, Hunter New England, John Hunter Hospital, New Lambton Heights, NSW, Australia Contact A/Prof James Scurry. E-mail: [email protected] 1. Coffin CM, Fletcher JA. Inflammatory myofibroblastic tumour. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon: IARC Press, 2013; 83–4. 2. Rabban JT, Zaloudek CJ, Shekitka KM, Tavassoli FA. Inflammatory myofibroblastictumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. Am J Surg Pathol 2005; 29: 1348–55. 3. Shintaku M, Fukushima A. Inflammatory myofibroblastictumor of the uterus with prominent myxoid change. Pathol Int 2006; 56: 625–8. 4. Cessna MH, Zhou H, Sanger WG, et al. Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases. Mod Pathol 2002; 15: 931–8. 5. Freeman A, Geddes N, Munson P, et al. Anaplastic lymphoma kinase (ALK 1) staining and molecular analysis in inflammatory myofibroblastic tumours of the bladder: a preliminary clinicopathological study of nine cases and review of the literature. Mod Pathol 2004; 17: 765–71. 6. Sukov WR, Cheville JC, Carlson AW, et al. Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastictumor from malignant spindle cell lesions of the urinary bladder. Mod Pathol 2007; 20: 592–603. 7. Montgomery EA, Shuster DD, Burkart AL, et al. Inflammatory myofibroblastictumors of the urinary tract: a clinicopathologic study of 46 cases, including a malignant example inflammatory fibrosarcoma and a subset associated with high-grade urothelial carcinoma. Am J Surg Pathol 2006; 30: 1502–12. 8. Li XQ, Hisaoka M, Shi DR, Zhu XZ, Hashimoto H. Expression of anaplastic lymphoma kinase in soft tissue tumors: an immunohistochemical and molecular study of 249 cases. Hum Pathol 2004; 35: 711–21.
DOI: 10.1097/PAT.0000000000000260
Tophaceous gout in the pelvis Sir, Gout is the clinical manifestation of hyperuricaemia and is characterised by the deposition of monosodium urate crystals in soft tissues, which invokes an inflammatory response.1 Hyperuricaemia occurs when there is an imbalance between uric acid production and excretion. For more than 90% of patients the primary problem is reduced renal excretion of uric acid.2 Gout usually presents acutely and intermittently as pain and swelling in and around joints of the distal extremities because uric acid precipitates first in relatively avascular, low temperature environments.3 Uncommonly, gout first presents in its chronic form as tophaceous gout, with no history of an acute intermittent stage.3–5 Rarely, tophaceous gout develops in deep soft
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
