270
Journal of the Royal Society of Medicine Volume 83 April 1990
Case reports I.I-'I
Thymoma with bone marrow eosinophilia
R J Fitzmaurice MB ChB D L Gardner MD PhD Department ofHistopathology, University Hospital of South Manchester, Nell Lane, West Didsbury, Manchester MZO 8LR Keywords: thymoma; eosinophilia Thymomas are uncommon neoplasms which occur at a mean age of 50 years1, rarely in children23 and have no sex or race predilection1'4. We describe a case of a benign thymoma, which initially presented radiographically and which, was found to be associated with a significantly increased proportion of eosinophils and precursors in the bone marrow. Case report An 83-year-old woman complained in 1986 of increasing breathlessness. Examination revealed cyanosis. Haemoglobin was 3.8 d/gl and white cell count 9.6x 109". In 1977, a lobulated lesion at the hilum of the left lung was noted radiographically. After further radiography and tomography, thymoma was diagnosed. The mass caused no respiratory embarrassment and resection was not advised. She developed severe cardiac failure and died. The cause of death' was pulmonary embolism. The left anterior mediastinum contained a firm, encapsulated, ovoid mass 12 cm across, the cut surface of which was lobulated and pale. Paraffin sections were stained with haematoxylin and eosin (HE), Grimelius and chromotrope 2R5. Immunocytochemical procedures for cytokeratin filaments (Dako Cytokeratin A575) were performed by the immunogold silver technique6 and for neuron specific enolase by the PAP method. The mediastinal mass was a lobular, cellular tumour composed of spindle-shaped, epithelial cells and a scanty lymphocyte infiltrate (Figure 1). The epithelial nature of the tumour cells was confirmed by positive cytokeratin staining7',. Grimelius and neuron-specific enolase stains were negative. The bone marrow was of high cellularity, with foci of lymphocytes and greatly increased numbers of eosinophil granulocytes and eosinophil myelocytes.
Figure 1. Thymoma. Spindle cell epithelial cells with scanty lymphocytic infiltrate, H&Ex288
Figure 2. Bone marrow. Cellular marrow with high proportion of eosinophil granulocytes, chromotrope 2Rx 732
Eosinophilic granules were clearly demonstrated using the chromotrope 2R stain (Figure 2). The proportion of eosinophils in the bone marrow was 10%, and focally up to 20-25%.
Discussion Thymoma implies a neoplasm of thymic epithelial cells, regardless of the propotion of lymphoqtes'O. True thymomas occur in 1 in 10 000 to 20 000 hospital admissions'0, and account for 20-25% of all mediastinal tumours2. Most are benign. The lymphocytes are not neoplastic and possess markers for normal thymocytes'. Malignant thymomas display little cytological atypia: recognition rests on the absence of an intact capsule or on lymphatic or haematogenous spread',2. Spindle cell thymomas account for 5-9% of these neoplasms; rarely invasive, they frequently are associated with a haematological or immunological disorder and seldom occur under 60 years2'7"'l. Haematological and immunological manifestations associated with thymoma almost always take the form of a decrease in the affected component. A case of thymoma with a polyclonal increase of IgG, IgA and IgM has been recorded, with neoplastic recurrence4 and two cases in which there was eosinophilic granulocytosis""'. In our case, there was a differential increase in the proportion of eosinophil and precursors in the bone marrow. This change was not noted in the peripheral blood, and there was no local, systemic or infective cause for peripheral eosinophilia and therefore, no explanation for bone marrow eosinophilia other than the presence of the thymoma. Possible reasons for the bone marrow eosinophilia include eosinophilic leukaemia and thymoma. The former is extremely rare and consistently displays peripheral leukocytosis. Leukaemia associated with thymoma is usually of acute lymphoblastic type. The latter appears to be a previously unrecorded association. Synthesis by the neoplasm of an eosinophil-stimulating factor is possible. The factor could derive either from the neoplastic cells themselves or from the associated lymphocytes. However, in a benign thymoma of spindlecell type, in which thymectomy and immunosuppression produced clinical remission", there was cell-mediated inhibition of erythropoiesis and in most published cases where thymoma has influenced the growth of lymphoreticular or haemopoietic cells, the influence ofthe neoplasm has been suppressive. Acknowledgments: The authors would like to thank Dr E Freeman for allowing us to report this case.
0141-0768/90/
040270-02/$02.00/0 © 1990 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 83 April 1990 References 1 Robbins SL, Cotran RS, Kumar V. Pathological basis ofdisease, 3rd edn. Philadelphia: WB Saunders, 1984:1250-2 2 Craig JB, Powell BC, Muss HB. Thymoma. Am Fam Physician 1984;29:229-34 3 Khope SS, Desmukh SS, Gandhi RK, Borwaukar SS, Kashyape S. Lymphocytic thymoma. Indian Pediatr 1984;21:977-81 4 Garfield GC. Thymoma: Unusual case and review of the literature. J Med Soc NJ 1983;80:826-8 5 Lendrum AC. The staining of eosinophil polymorphs and enterochromaffin cells in histological sections. J Pathol Bact 1944;56: 441 6 Holgate CS, Jackson P, Cowen PN, Bird CC. Immunogoldsilver staining: a new method of immunostaining with enhanced sensitivity. J Histochem Cytochem 1983;31:938-44 7 Ring NP, Addis BJ. Thymoma: an integrated clinico-pathological and immunohistochemical study. J Pathol 1986;149:327-37 8 Kodama T, Watanabe S, Sato Y, Shimosata Y, Miyazawa N. An immunohistochemical study of thymic epithelial tumours, I. Epithelial component. Am J Surg Pathol 1986;10:26-33
271
9 Rosai J, Levine CP. Tumours of the thymus. In: Atlas of tumour pathology, 2nd series. 1976:34-7 Fasc. 13 AFIP Washington DC 10 Kissane JM, ed. Anderson's pathology, 8th edn. St. Louis: CV Mosby, 1985:1362-5 11 Blom P, Johannessen JV. A tumour ofthe anterior mediastinum. Pathol Res Pract 1983;178:83-5 12 Mitchell EB, Platts-Mills JA, Pereira RS, Malkovska V, Webster AD. Acquired basophil and eosinophil deficiency in a patient with hypogammaglobulinaemia assocated with thymoma. Clin Lab Haematol 1983;5:253-7 13 Juhlin L, Michaelson G. A new syndrome characterized by absence of eosinophils and basophils. Lancet 1977;i:1233-5 14 Milnes JP, Goorney BP, Wallington TB. Pure red cell aplasia and thymoma associated with high levels of the suppresor/ cytotoxic T lymphocyte subset. Br Med J 1984289:1333-4 (Accepted 10 February 1989. Correspondence to Dr R JFitzmaurice, Department of Pathological Sciences, The Medical School, Stopford Buikling, Uniesity of Mahester, Oxford Road, Manchester M13 9P7)
Enalapril-related cholestatic jaundice \
Journal of the Royal Society of Medicine Volume 83 April 1990
Case reports I.I-'I
Thymoma with bone marrow eosinophilia
R J Fitzmaurice MB ChB D L Gardner MD PhD Department ofHistopathology, University Hospital of South Manchester, Nell Lane, West Didsbury, Manchester MZO 8LR Keywords: thymoma; eosinophilia Thymomas are uncommon neoplasms which occur at a mean age of 50 years1, rarely in children23 and have no sex or race predilection1'4. We describe a case of a benign thymoma, which initially presented radiographically and which, was found to be associated with a significantly increased proportion of eosinophils and precursors in the bone marrow. Case report An 83-year-old woman complained in 1986 of increasing breathlessness. Examination revealed cyanosis. Haemoglobin was 3.8 d/gl and white cell count 9.6x 109". In 1977, a lobulated lesion at the hilum of the left lung was noted radiographically. After further radiography and tomography, thymoma was diagnosed. The mass caused no respiratory embarrassment and resection was not advised. She developed severe cardiac failure and died. The cause of death' was pulmonary embolism. The left anterior mediastinum contained a firm, encapsulated, ovoid mass 12 cm across, the cut surface of which was lobulated and pale. Paraffin sections were stained with haematoxylin and eosin (HE), Grimelius and chromotrope 2R5. Immunocytochemical procedures for cytokeratin filaments (Dako Cytokeratin A575) were performed by the immunogold silver technique6 and for neuron specific enolase by the PAP method. The mediastinal mass was a lobular, cellular tumour composed of spindle-shaped, epithelial cells and a scanty lymphocyte infiltrate (Figure 1). The epithelial nature of the tumour cells was confirmed by positive cytokeratin staining7',. Grimelius and neuron-specific enolase stains were negative. The bone marrow was of high cellularity, with foci of lymphocytes and greatly increased numbers of eosinophil granulocytes and eosinophil myelocytes.
Figure 1. Thymoma. Spindle cell epithelial cells with scanty lymphocytic infiltrate, H&Ex288
Figure 2. Bone marrow. Cellular marrow with high proportion of eosinophil granulocytes, chromotrope 2Rx 732
Eosinophilic granules were clearly demonstrated using the chromotrope 2R stain (Figure 2). The proportion of eosinophils in the bone marrow was 10%, and focally up to 20-25%.
Discussion Thymoma implies a neoplasm of thymic epithelial cells, regardless of the propotion of lymphoqtes'O. True thymomas occur in 1 in 10 000 to 20 000 hospital admissions'0, and account for 20-25% of all mediastinal tumours2. Most are benign. The lymphocytes are not neoplastic and possess markers for normal thymocytes'. Malignant thymomas display little cytological atypia: recognition rests on the absence of an intact capsule or on lymphatic or haematogenous spread',2. Spindle cell thymomas account for 5-9% of these neoplasms; rarely invasive, they frequently are associated with a haematological or immunological disorder and seldom occur under 60 years2'7"'l. Haematological and immunological manifestations associated with thymoma almost always take the form of a decrease in the affected component. A case of thymoma with a polyclonal increase of IgG, IgA and IgM has been recorded, with neoplastic recurrence4 and two cases in which there was eosinophilic granulocytosis""'. In our case, there was a differential increase in the proportion of eosinophil and precursors in the bone marrow. This change was not noted in the peripheral blood, and there was no local, systemic or infective cause for peripheral eosinophilia and therefore, no explanation for bone marrow eosinophilia other than the presence of the thymoma. Possible reasons for the bone marrow eosinophilia include eosinophilic leukaemia and thymoma. The former is extremely rare and consistently displays peripheral leukocytosis. Leukaemia associated with thymoma is usually of acute lymphoblastic type. The latter appears to be a previously unrecorded association. Synthesis by the neoplasm of an eosinophil-stimulating factor is possible. The factor could derive either from the neoplastic cells themselves or from the associated lymphocytes. However, in a benign thymoma of spindlecell type, in which thymectomy and immunosuppression produced clinical remission", there was cell-mediated inhibition of erythropoiesis and in most published cases where thymoma has influenced the growth of lymphoreticular or haemopoietic cells, the influence ofthe neoplasm has been suppressive. Acknowledgments: The authors would like to thank Dr E Freeman for allowing us to report this case.
0141-0768/90/
040270-02/$02.00/0 © 1990 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 83 April 1990 References 1 Robbins SL, Cotran RS, Kumar V. Pathological basis ofdisease, 3rd edn. Philadelphia: WB Saunders, 1984:1250-2 2 Craig JB, Powell BC, Muss HB. Thymoma. Am Fam Physician 1984;29:229-34 3 Khope SS, Desmukh SS, Gandhi RK, Borwaukar SS, Kashyape S. Lymphocytic thymoma. Indian Pediatr 1984;21:977-81 4 Garfield GC. Thymoma: Unusual case and review of the literature. J Med Soc NJ 1983;80:826-8 5 Lendrum AC. The staining of eosinophil polymorphs and enterochromaffin cells in histological sections. J Pathol Bact 1944;56: 441 6 Holgate CS, Jackson P, Cowen PN, Bird CC. Immunogoldsilver staining: a new method of immunostaining with enhanced sensitivity. J Histochem Cytochem 1983;31:938-44 7 Ring NP, Addis BJ. Thymoma: an integrated clinico-pathological and immunohistochemical study. J Pathol 1986;149:327-37 8 Kodama T, Watanabe S, Sato Y, Shimosata Y, Miyazawa N. An immunohistochemical study of thymic epithelial tumours, I. Epithelial component. Am J Surg Pathol 1986;10:26-33
271
9 Rosai J, Levine CP. Tumours of the thymus. In: Atlas of tumour pathology, 2nd series. 1976:34-7 Fasc. 13 AFIP Washington DC 10 Kissane JM, ed. Anderson's pathology, 8th edn. St. Louis: CV Mosby, 1985:1362-5 11 Blom P, Johannessen JV. A tumour ofthe anterior mediastinum. Pathol Res Pract 1983;178:83-5 12 Mitchell EB, Platts-Mills JA, Pereira RS, Malkovska V, Webster AD. Acquired basophil and eosinophil deficiency in a patient with hypogammaglobulinaemia assocated with thymoma. Clin Lab Haematol 1983;5:253-7 13 Juhlin L, Michaelson G. A new syndrome characterized by absence of eosinophils and basophils. Lancet 1977;i:1233-5 14 Milnes JP, Goorney BP, Wallington TB. Pure red cell aplasia and thymoma associated with high levels of the suppresor/ cytotoxic T lymphocyte subset. Br Med J 1984289:1333-4 (Accepted 10 February 1989. Correspondence to Dr R JFitzmaurice, Department of Pathological Sciences, The Medical School, Stopford Buikling, Uniesity of Mahester, Oxford Road, Manchester M13 9P7)
Enalapril-related cholestatic jaundice \
