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EQUINE VETERINARY JOURNAL Equine vet. J . (1992) 24 (6) 492-493
Pulmonary plasma cell granuloma (inflammatory pseudotumour) in a horse R. F. SLOCOMBE, C. L. MILLER’ and A. A. MACLEAN Veterinary Clinical Centre, University of Melbourne, Princes Hlghwax Werribee, Victoria 3030, Australia. Introduction Plasma cell granulomas are rare benign lesions that have been reported with greatest frequency in children (Bahadori and Liebow 1973; Berardi et al. 1983; Spencer 1984; Lebecque et al. 1987). They have not been previously reported in animals. The classification of the condition remains difficult and at least 17 different terms have been used in naming this lesion (Bahadori and Liebow 1983; Berardi et a l . 1983; Spencer 1984). These masses are thought to arise as a consequence of an atypical inflammatory response.
Case Report
frequently indented. Poorly formed capillaries and haemorrhages were common, and the mass contained numerous small collections of lymphocytes, macrophages and plasma cells, with lesser numbers of neutrophils, eosinophils and mast cells (Fig 4). Towards the periphery, tissues were less oedematous and consisted of dense connective tissue, with foci of hyalinisation. Transmission electron microscopy of formalin-fixed portions of the mass revealed a mixed population of cells, most of which lacked tight junctions, and which contained prominent granular endoplasmic reticulum. No intracellular filaments were seen. Many pyrinophilic cells were present within the mass, although not all were morphologically compatible with plasma cells. Immunoperoxidase stains for gamma globulins, using formalin-
A Thoroughbred gelding, aged 6 years, was admitted to the Veterinary Clinical Centre, University of Melbourne, Werribee, following lameness over the previous 7 weeks caused by swelling of the distal parts of all limbs. There were also intermittent bouts of epistaxis. Radiographs of the lower limbs confirmed that the swelling was associated with subperiosteal new bone formation. Thoracic radiographs showed the presence of a large pulmonary mass dorsal to the heart. Fibre-optic examination of the respiratory tract showed that blood was coming from the lungs. A pulmonary neoplasm was suspected, the animal was subjected to euthanasia by barbiturate overdosage and a necropsy performed.
Pathology Significant pulmonary changes consisted of a solitary, well circumscribed mass, 15 cm in diameter, in the dorsal aspect of the left lung, adjacent to the tracheal bifurcation (Fig 1). Adjacent pleural lymphatics an veins were tortuous and distended but the remainder of the lung, bronchial lymph nodes and mediastinal tissues were unremarkable. The lung mass had a necrotic centre filled with blood; surrounding tissue was tan, friable and soft, about 2 cm thick, with a thin outer zone of fibrous connective tissue. No discrete site for the pulmonary haemorrhage was found. Bones distal to the carpi and tarsi had irregular subperiosteal proliferations of new bone up to 1 cm thick, with increased density of adjacent fibrous connective tissue. Joint capsules were involved at the points of attachment to the bones, but articular surfaces were unaffected. Histopathological examination confirmed the presence of subperiosteal new bone involving the bones of the distal limbs. The lung mass was characterised by oedematous inflamed granulation tissue. Pleomorphic populations of generally fusiform cells were loosely arranged in whorls and intersecting fascicles in a poorly developed storiform pattern (Figs 2 and 3). Mitotic figures were scarce, and cell nuclei were round to oval and ‘Present address: Veterinary Teaching Hospital, Colorado State University, Fort Collins, Colorado 80523, USA.
Fig I : A large mass from the dorsal aspect of the lef! lung. The lesion has dark mottled areas of necrosis and haemorrhage. Bar = 10 cm
Fig 2: Arrangement of granulation tissue in a loose sroriform pattern with interspersed inflammatory c e l l s . Haematoxylin and eosin (H&E),x125
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EQUINE VETERINARY JOURNAL
Fig 3: Granulation tissue and lymphoplasmacytic infiltrates. H&E, x 315
immunofluorescence to determine whether polyclonal immunoglobulins were present within cells of the mass. No staining was observed, even in cells that were morphologically compatible with mature plasma cells, and the negative result was therefore considered erroneous, presumably because of the detrimental effects of formalin fixation on antigen presentation. The biological cause of this lesion is generally benign, although malignant transformation and recurrence after surgical excision have been reported (Spencer 1984; Warter et a/. 1987; Weinberg ef a/. 1987). There is conflicting evidence regarding an association with previous pulmonary infections (Berardi et al. 1983), but the lesion has been associated with infections in a few instances (Berardi et al. 1983; Janigan and Marie 1983; Harjula et al. 1986). Pulmonary osteoarthropathy in children is not uncommon in association with this condition, and in a recent case, disturbances in mineral metabolism were associated with production of 1.25dihydroxy vitamin D3 by plasma cells which had induced hypercalcaemia (Helikson et al. 1986). The clinical and pathological features of this case are similar to those reported for plasma cell granulomas of children. The differential diagnosis includes abscesses and benign and malignant neoplasms, especially those of lymphoreticular or connective tissue origin. Indeed, plasma cell granulomas might be easily mistaken for inflamed benign connective tissue neoplasms, except that such neoplasms are not generally associated with widespread intense vascular and inflammatory cell infiltration. This report should familiarise veterinary pathologists with the condition and documents the first case in a horse.
Acknowledgements Fig 4: Derail of inflammatory cells: many cells are plasma interspersed between of irregular clusters fibroblasts. H & E , x 750
We thank Dr P. Ironside, Peter MacCallum Institute, Melbourne, for advice on the diagnosis of this tumour; Mr P. Crammer for assistance with the photographs; and Dr R. W. Fisher for the case referral.
References fixed tissues, were negative (courtesy of Dr Michael Day, Division of Veterinary Biology, School of Veterinary Studies, Murdoch, Western Australia).
Bahadori, M. and Liebow. A.A. (1973)Plasma cell granulomas of the lung. Cancer
Discussion
Berardi, R.S., Lee, S.S., Chen. H.P. and Stines, E.J. (1983) Inflammatory pseudotumours of the lung. Surg. Cynecol. Ohstet. 156,89-96. Fassina, S.A., Rugge, M., Scapinello. A., Viale. 0.. Dell'Orto, P. and Ninfo, V. (1986)Plasma cell granuloma of the lung (Inflammatory Pseudotumor). Tumor
In children, plasma cell granulomas often present with the symptoms of persistent cough, thoracic pain, fever, haemoptysis, dyspnoea, malaise and clubbing of the digits (Berardi et al. 1983; Spencer 1984; Lebecque et a/. 1987). Radiographically, plasma cell granulomas appear as well delineated, round, solitary intrapulmonary masses (Berardi et a/. 1983). Histologically, at least three cell types are round in plasma cell granulomas, including lymphocytes, plasma cells, macrophages and fibroblasts. Great variability in the appearance and arrangement of these cells has led to many classifications of this lesion. Plasma cell granuloma and inflammatory pseudotumour are the two most commonly accepted names at this time (Bahadori and Liebow 1973; Berardi et a/. 1983). The pathogenesis of these masses remains uncertain. Positive intermediate filament staining for vimentin by immunofluorescence confirms their mesenchymal derivation (Huszar et a/. 1986) and in tissue culture, the pattern of this growth is typical for granulation tissue (Fernandez and Escanola-Zapata 1983). Their inflammatory nature is further supported by the polyclonal nature of the immunoglobulins produced by the plasma cells in the mass (Monzon et a/. 1982; Fassina et a/. 1986) and also because they bear some similarity to lesions produced in mice following intrapulmonary inoculation with Freunds complete adjuvant (Hamamoto er al. 1983). An attempt was made using indirect
31,191-208.
72,529-534.
-
Fernandez, E.A. and Escalona-Zapata, 1. (1983)Pulmonary plasma cell granuloma an electron microscopic and tissue culture study. Histopathalogy 7.279-286. Hamamoto, Y., Hashimoto, K.. Baba, M.. Kinoshita, K. and Yasuhira, K. (1983) Experimental production of pulmonary granulomas: 111 Plasma cell granulomas in mice. Br. J. exp. Path. 64.93-99. Harjula, A., Mattila. S.. Kyosola. K.. Heikkila. L. and Milkinen, J. (1986)Plasma cell granuloma of lung and pleura. Scand. J. rhor. cardiovasc.Surg. 20, 119-121. Helikson. M.A.. Havey, A.D., Zenvekh. J.E., Breslau, N.A. and Gardner, D.W. (1986)Plasma cell granuloma producing calcitriol and hypercalcaemia. Ann. int. Med. 105,379-38I. Huszar. M., Suster. S., Herczeg. E. and Geiger, B. (1986)Sclerosing hemangioma of the lung. Cancer 58,2422-2427. Janigan, D.T. and Mane, T.J.(1983)An inflammatory pseudotumor of lung in Q Fever pneumonia. New Engl. J. Med. 308.86-88. Lebecque, P., Lapieme, J.G., Brochu. P.. Spiers, S. and Lamane, A. (1987) Pulmonary plasma cell granuloma. Eur. J. Paediarr. 146, 174-176. Monzon, C.M., Gilchrist, G.S., Burgert, E.O.. OConnell, E.J., Telander. R.L.. Hoffman, A.D. and Li, C-Y. (1982)Plasma cell granuloma in the lung of children. Pediarrics 70,268-274. Spencer, H. (1984) The pulmonary plasma cellhistiocytoma complex. HisfopatholoRy8., 903-916. Warter, A., Satge, D. and Roeslin. N. (1987)Angio invasive plasma cell granulomas of the lung. Cancer 59,435-443. Weinberg, P.B.. Bromberg, P.A. and Askin, F.B. (1987)Recumnce of a plasma cell granuloma 1 I years after initial resection. Southern med. J. 80.519-521.
EQUINE VETERINARY JOURNAL Equine vet. J . (1992) 24 (6) 492-493
Pulmonary plasma cell granuloma (inflammatory pseudotumour) in a horse R. F. SLOCOMBE, C. L. MILLER’ and A. A. MACLEAN Veterinary Clinical Centre, University of Melbourne, Princes Hlghwax Werribee, Victoria 3030, Australia. Introduction Plasma cell granulomas are rare benign lesions that have been reported with greatest frequency in children (Bahadori and Liebow 1973; Berardi et al. 1983; Spencer 1984; Lebecque et al. 1987). They have not been previously reported in animals. The classification of the condition remains difficult and at least 17 different terms have been used in naming this lesion (Bahadori and Liebow 1983; Berardi et a l . 1983; Spencer 1984). These masses are thought to arise as a consequence of an atypical inflammatory response.
Case Report
frequently indented. Poorly formed capillaries and haemorrhages were common, and the mass contained numerous small collections of lymphocytes, macrophages and plasma cells, with lesser numbers of neutrophils, eosinophils and mast cells (Fig 4). Towards the periphery, tissues were less oedematous and consisted of dense connective tissue, with foci of hyalinisation. Transmission electron microscopy of formalin-fixed portions of the mass revealed a mixed population of cells, most of which lacked tight junctions, and which contained prominent granular endoplasmic reticulum. No intracellular filaments were seen. Many pyrinophilic cells were present within the mass, although not all were morphologically compatible with plasma cells. Immunoperoxidase stains for gamma globulins, using formalin-
A Thoroughbred gelding, aged 6 years, was admitted to the Veterinary Clinical Centre, University of Melbourne, Werribee, following lameness over the previous 7 weeks caused by swelling of the distal parts of all limbs. There were also intermittent bouts of epistaxis. Radiographs of the lower limbs confirmed that the swelling was associated with subperiosteal new bone formation. Thoracic radiographs showed the presence of a large pulmonary mass dorsal to the heart. Fibre-optic examination of the respiratory tract showed that blood was coming from the lungs. A pulmonary neoplasm was suspected, the animal was subjected to euthanasia by barbiturate overdosage and a necropsy performed.
Pathology Significant pulmonary changes consisted of a solitary, well circumscribed mass, 15 cm in diameter, in the dorsal aspect of the left lung, adjacent to the tracheal bifurcation (Fig 1). Adjacent pleural lymphatics an veins were tortuous and distended but the remainder of the lung, bronchial lymph nodes and mediastinal tissues were unremarkable. The lung mass had a necrotic centre filled with blood; surrounding tissue was tan, friable and soft, about 2 cm thick, with a thin outer zone of fibrous connective tissue. No discrete site for the pulmonary haemorrhage was found. Bones distal to the carpi and tarsi had irregular subperiosteal proliferations of new bone up to 1 cm thick, with increased density of adjacent fibrous connective tissue. Joint capsules were involved at the points of attachment to the bones, but articular surfaces were unaffected. Histopathological examination confirmed the presence of subperiosteal new bone involving the bones of the distal limbs. The lung mass was characterised by oedematous inflamed granulation tissue. Pleomorphic populations of generally fusiform cells were loosely arranged in whorls and intersecting fascicles in a poorly developed storiform pattern (Figs 2 and 3). Mitotic figures were scarce, and cell nuclei were round to oval and ‘Present address: Veterinary Teaching Hospital, Colorado State University, Fort Collins, Colorado 80523, USA.
Fig I : A large mass from the dorsal aspect of the lef! lung. The lesion has dark mottled areas of necrosis and haemorrhage. Bar = 10 cm
Fig 2: Arrangement of granulation tissue in a loose sroriform pattern with interspersed inflammatory c e l l s . Haematoxylin and eosin (H&E),x125
493
EQUINE VETERINARY JOURNAL
Fig 3: Granulation tissue and lymphoplasmacytic infiltrates. H&E, x 315
immunofluorescence to determine whether polyclonal immunoglobulins were present within cells of the mass. No staining was observed, even in cells that were morphologically compatible with mature plasma cells, and the negative result was therefore considered erroneous, presumably because of the detrimental effects of formalin fixation on antigen presentation. The biological cause of this lesion is generally benign, although malignant transformation and recurrence after surgical excision have been reported (Spencer 1984; Warter et a/. 1987; Weinberg ef a/. 1987). There is conflicting evidence regarding an association with previous pulmonary infections (Berardi et al. 1983), but the lesion has been associated with infections in a few instances (Berardi et al. 1983; Janigan and Marie 1983; Harjula et al. 1986). Pulmonary osteoarthropathy in children is not uncommon in association with this condition, and in a recent case, disturbances in mineral metabolism were associated with production of 1.25dihydroxy vitamin D3 by plasma cells which had induced hypercalcaemia (Helikson et al. 1986). The clinical and pathological features of this case are similar to those reported for plasma cell granulomas of children. The differential diagnosis includes abscesses and benign and malignant neoplasms, especially those of lymphoreticular or connective tissue origin. Indeed, plasma cell granulomas might be easily mistaken for inflamed benign connective tissue neoplasms, except that such neoplasms are not generally associated with widespread intense vascular and inflammatory cell infiltration. This report should familiarise veterinary pathologists with the condition and documents the first case in a horse.
Acknowledgements Fig 4: Derail of inflammatory cells: many cells are plasma interspersed between of irregular clusters fibroblasts. H & E , x 750
We thank Dr P. Ironside, Peter MacCallum Institute, Melbourne, for advice on the diagnosis of this tumour; Mr P. Crammer for assistance with the photographs; and Dr R. W. Fisher for the case referral.
References fixed tissues, were negative (courtesy of Dr Michael Day, Division of Veterinary Biology, School of Veterinary Studies, Murdoch, Western Australia).
Bahadori, M. and Liebow. A.A. (1973)Plasma cell granulomas of the lung. Cancer
Discussion
Berardi, R.S., Lee, S.S., Chen. H.P. and Stines, E.J. (1983) Inflammatory pseudotumours of the lung. Surg. Cynecol. Ohstet. 156,89-96. Fassina, S.A., Rugge, M., Scapinello. A., Viale. 0.. Dell'Orto, P. and Ninfo, V. (1986)Plasma cell granuloma of the lung (Inflammatory Pseudotumor). Tumor
In children, plasma cell granulomas often present with the symptoms of persistent cough, thoracic pain, fever, haemoptysis, dyspnoea, malaise and clubbing of the digits (Berardi et al. 1983; Spencer 1984; Lebecque et a/. 1987). Radiographically, plasma cell granulomas appear as well delineated, round, solitary intrapulmonary masses (Berardi et a/. 1983). Histologically, at least three cell types are round in plasma cell granulomas, including lymphocytes, plasma cells, macrophages and fibroblasts. Great variability in the appearance and arrangement of these cells has led to many classifications of this lesion. Plasma cell granuloma and inflammatory pseudotumour are the two most commonly accepted names at this time (Bahadori and Liebow 1973; Berardi et a/. 1983). The pathogenesis of these masses remains uncertain. Positive intermediate filament staining for vimentin by immunofluorescence confirms their mesenchymal derivation (Huszar et a/. 1986) and in tissue culture, the pattern of this growth is typical for granulation tissue (Fernandez and Escanola-Zapata 1983). Their inflammatory nature is further supported by the polyclonal nature of the immunoglobulins produced by the plasma cells in the mass (Monzon et a/. 1982; Fassina et a/. 1986) and also because they bear some similarity to lesions produced in mice following intrapulmonary inoculation with Freunds complete adjuvant (Hamamoto er al. 1983). An attempt was made using indirect
31,191-208.
72,529-534.
-
Fernandez, E.A. and Escalona-Zapata, 1. (1983)Pulmonary plasma cell granuloma an electron microscopic and tissue culture study. Histopathalogy 7.279-286. Hamamoto, Y., Hashimoto, K.. Baba, M.. Kinoshita, K. and Yasuhira, K. (1983) Experimental production of pulmonary granulomas: 111 Plasma cell granulomas in mice. Br. J. exp. Path. 64.93-99. Harjula, A., Mattila. S.. Kyosola. K.. Heikkila. L. and Milkinen, J. (1986)Plasma cell granuloma of lung and pleura. Scand. J. rhor. cardiovasc.Surg. 20, 119-121. Helikson. M.A.. Havey, A.D., Zenvekh. J.E., Breslau, N.A. and Gardner, D.W. (1986)Plasma cell granuloma producing calcitriol and hypercalcaemia. Ann. int. Med. 105,379-38I. Huszar. M., Suster. S., Herczeg. E. and Geiger, B. (1986)Sclerosing hemangioma of the lung. Cancer 58,2422-2427. Janigan, D.T. and Mane, T.J.(1983)An inflammatory pseudotumor of lung in Q Fever pneumonia. New Engl. J. Med. 308.86-88. Lebecque, P., Lapieme, J.G., Brochu. P.. Spiers, S. and Lamane, A. (1987) Pulmonary plasma cell granuloma. Eur. J. Paediarr. 146, 174-176. Monzon, C.M., Gilchrist, G.S., Burgert, E.O.. OConnell, E.J., Telander. R.L.. Hoffman, A.D. and Li, C-Y. (1982)Plasma cell granuloma in the lung of children. Pediarrics 70,268-274. Spencer, H. (1984) The pulmonary plasma cellhistiocytoma complex. HisfopatholoRy8., 903-916. Warter, A., Satge, D. and Roeslin. N. (1987)Angio invasive plasma cell granulomas of the lung. Cancer 59,435-443. Weinberg, P.B.. Bromberg, P.A. and Askin, F.B. (1987)Recumnce of a plasma cell granuloma 1 I years after initial resection. Southern med. J. 80.519-521.
