G Model PRP-51409; No. of Pages 4
ARTICLE IN PRESS Pathology – Research and Practice xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Pathology – Research and Practice journal homepage: www.elsevier.com/locate/prp
Teaching cases
Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass Junko Ito a , Akihiko Yoshida a , Akiko Miyagi Maeshima a , Kazuo Nakagawa b , Shun-ichi Watanabe b , Yukio Kobayashi c , Suguru Fukuhara c , Koji Tsuta a,∗ a
Division of Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo 104-0045, Japan c Department of Hematology, National Cancer Center Hospital, Tokyo 104-0045, Japan b
a r t i c l e
i n f o
Article history: Received 25 March 2015 Received in revised form 17 May 2015 Accepted 5 June 2015 Keywords: Thymus Thymoma T lymphoblastic leukemia/lymphoma Thymic carcinoma
a b s t r a c t We report a case of a 62-year-old man with concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma. Computed tomography revealed a 5.5-cm anterior mediastinal mass, and surgical resection was performed. Histologically, the mass showed concurrent thymoma (type AB), thymic carcinoma, and T lymphoblastic leukemia/lymphoma. Lymphoma cells infiltrated in the left lung, pulmonary hilar lymph nodes, and involved bone marrow. The patient underwent chemotherapy for T lymphoblastic leukemia/lymphoma and achieved remission. One year after surgery, he remains free of both thymoma and thymic carcinoma, and T lymphoblastic leukemia/lymphoma remains complete remission under maintenance therapy. Thymoma and T lymphoblastic leukemia/lymphoma can combine in the same mass, although this is quite rare. At the time of the diagnosis of thymoma, additional attention should be directed toward lymphocytes in the background. © 2015 Elsevier GmbH. All rights reserved.
1. Introduction Thymoma is a neoplasm that originates from thymic epithelial cells and is frequently associated with mature or immature non-neoplastic lymphocytes. On the other hand, T lymphoblastic leukemia/lymphoma is a neoplasm of lymphoblasts committed to the T-cell lineage, and it frequently shows mediastinal involvement. The distinction between thymoma and T lymphoblastic leukemia/lymphoma is occasionally difficult, because the immature lymphocytes associated with thymoma may resemble T lymphoblastic leukemia/lymphoma cells, both morphologically and immunohistochemically. Here, we report an extraordinary case of concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma presenting as an anterior mediastinal mass.
mass in the left anterior mediastinum. Surgical resection for the mass was performed in addition to the lobectomy of the left upper lobe of the lung; pulmonary hilar lymph nodes were also dissected. On post-operative day 6, the platelet counts decreased markedly (from 314,000/l before surgery to 77,000/l on day 6). Because the possibility of hematologic malignancy could not be excluded as the cause of the thrombocytopenia, bone marrow aspiration was performed from the ilium, which lead to the diagnosis of T lymphoblastic leukemia/lymphoma. There were no blast cells in the peripheral blood. The patient underwent chemotherapy for T lymphoblastic leukemia/lymphoma, and achieved remission. One year after surgery, he remains free of both thymoma and thymic carcinoma, and T lymphoblastic leukemia/lymphoma remains in complete remission under maintenance therapy. Informed consent was obtained from the patient for publication of this case report.
2. Clinical history A 62-year-old man complained of fever and chest pain. Computed tomography (CT) scan of the chest demonstrated a 5.5-cm
∗ Corresponding author at: The Division of Pathology, National Cancer Center Hospital, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. Tel.: +81 3 3542 2511; fax: +81 3 3545 3567. E-mail address: [email protected] (K. Tsuta).
3. Pathological findings Grossly, the resected specimen showed a multinodular tumor in the anterior mediastinum, measuring 9.2 cm × 5.7 cm × 5.2 cm. The cut surface of the tumor was multiple tan-colored nodules with fibrosis and necrosis (Fig. 1). The tumor was encapsulated, but the demarcation from the lung and fat tissue was partly ill-defined.
http://dx.doi.org/10.1016/j.prp.2015.06.002 0344-0338/© 2015 Elsevier GmbH. All rights reserved.
Please cite this article in press as: J. Ito, et al., Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass, Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.06.002
G Model PRP-51409; No. of Pages 4
ARTICLE IN PRESS
2
J. Ito et al. / Pathology – Research and Practice xxx (2015) xxx–xxx
Fig. 1. The gross cut surface of the tumor showed multiple tan-colored nodules with fibrosis and necrosis. In inset, the components of thymoma and thymic carcinoma were shown with white and red, respectively. The rest of the tumor consisted of fibrosis and necrosis, which was shown with green oblique lines. The capsule of the thymoma was indicated with black line. The infiltration of T lymphoblastic leukemia/lymphoma cells was shown with blue dots. (For interpretation of the references to color in figure legend, the reader is referred to the web version of the article.)
Histologically, approximately 30% of the mediastinal tumor showed features of type AB thymoma, consisting of a mixture of lymphocyte-poor type A thymoma component and lymphocyterich type B thymoma-like component. Type A thymoma component showed diffuse growth of short spindle cells with focal rosettelike structures and a few mature lymphocytes (Fig. 2A and B). Type B thymoma-like component showed scattered polygonal or round epithelial cells in a prominent population of lymphocytes (Fig. 2C). The epithelial tumor cells were immunopositive for AE1/AE3 cytokeratins (Fig. 2D), p40, and focally positive for CD20. Foci of microinvasion into perithymic adipose tissue and left lung parenchyma were noted. In addition to the above thymoma morphology, multiple nests of malignant component were noted, in which pleomorphic cells proliferated (Fig. 2E and F). These areas were poorly differentiated thymic squamous cell carcinomas, and the diagnosis was immunohistochemically supported by focal positivity to CD5 and p40. The thymic carcinoma component accounted for approximately 5% of the mediastinal tumor. The rest of the tumor consisted of fibrosis and necrosis. We also noted a mix of atypical lymphocytes and small nonatypical lymphocytes in the background of the thymoma. The atypical lymphocytes showed medium-sized, irregular-shaped nuclei with condensed chromatin and mitotic activity (Fig. 3A). These cells infiltrated into the left lung and the pulmonary hilar lymph nodes without accompanying epithelial tumor cells (Fig. 3B and C). Both atypical and non-atypical lymphocytes were positive for TdT (Fig. 3A inset), CD1a, CD99, CD5, CD3, CD7, CD4, and CD8, but they were negative for CD20. Clonal rearrangement of the T-cell receptor  chain gene was identified from the atypical lymphocytes by polymerase chain reaction (PCR), and these cells were diagnosed as T lymphoblastic leukemia/lymphoma. T lymphoblastic leukemia/lymphoma cells accounted for approximately 70% of the lymphocytes in the background of the thymoma, and infiltrated
into the adjacent left lung and the pulmonary hilar lymph nodes. Bone marrow aspiration revealed that lymphoblasts represented 83% of the bone marrow (Fig. 3D). 4. Discussion Both thymoma and T lymphoblastic leukemia/lymphoma arise in mediastinum, and the immature lymphocytes associated with thymoma may resemble T lymphoblastic leukemia/lymphoma cells. Therefore, it is occasionally difficult to distinguish these two lesions. The presence of neoplastic epithelial cells in thymoma is the important clue for distinguishing thymoma from T lymphoblastic leukemia/lymphoma. In our case, epithelial cells were diffusely present in the mediastinal mass, but only atypical lymphocytes infiltrated into the lung, lymph nodes, and bone marrow without epithelial cells. Furthermore, molecular genetic analyses revealed clonal rearrangement of the T-cell receptor  chain gene. These findings altogether helped us make definitive diagnosis of concurrent thymoma and T lymphoblastic leukemia/lymphoma. Concurrent thymoma and malignant leukemia/lymphoma is rare [1–7], and only two reports have previously described the coexistence of thymoma and T lymphoblastic leukemia/lymphoma in the same lesion [4,6]. Although the pathogenesis of concurrent thymoma and T lymphoblastic leukemia/lymphoma is still unclear, two theories are conceivable. First, lymphocytes in the thymoma may have transformed into T lymphoblastic leukemia/lymphoma [1,4,7,8]. Second, T lymphoblastic leukemia/lymphoma may have occurred coincidentally, and infiltrated into the thymoma [7]. The neoplastic epithelial cells of thymoma may retain the function of attracting immature T cells, akin to the normal thymus. In some previously reported cases, malignant lymphoma/leukemia arose after chemotherapy or radiation therapy for thymoma, and some authors have discussed the possibility of secondary malignant lymphoma
Please cite this article in press as: J. Ito, et al., Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass, Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.06.002
G Model PRP-51409; No. of Pages 4
ARTICLE IN PRESS J. Ito et al. / Pathology – Research and Practice xxx (2015) xxx–xxx
3
Fig. 2. Histological findings of the type AB thymoma and thymic carcinoma. (A) Type A thymoma component showed diffuse growth of short spindle cells with a few mature lymphocytes (HE, 200×). (B) The tumor cells partly formed rosette-like structures in the type A thymoma component (HE, 200×). (C) Type B thymoma-like component showed scattered polygonal or round epithelial cells in a prominent population of lymphocytes (HE, 200×). (D) The epithelial tumor cells were positive for AE1/AE3 cytokeratins (200×). (E) The nests of the thymic carcinoma (left side) were adjacent to thymoma (right side) (HE, 100×). (F) High-power view of the thymic carcinoma showed pleomorphic malignant cells arranged in the nest. Mitotic figures were frequently encountered (HE, 200×).
that is triggered by thymoma treatment [4,7]. However, our patient did not receive any treatment before surgery. In the present case, the possibility of T-cell lymphocytosis was initially considered. This is a phenomenon in which polyclonal, non-neoplastic T cells proliferate in peripheral blood, bone marrow and other parenchymal organs, usually associated with lymphocyte-rich and invasive thymoma. Although this phenomenon is very rare, a few cases have been reported [9,10]. However, this is not applicable to our case because we observed clonal rearrangement of the T-cell receptor  chain gene. In addition to thymoma and T lymphoblastic leukemia/ lymphoma, thymic carcinoma was also present in our case. On rare occasions, thymoma can undergo malignant transformation into
thymic carcinoma [11,12]. However, the literature does not include any reports of the coexistence of thymic carcinoma and malignant lymphoma. In our patient, T lymphoblastic leukemia/lymphoma did not infiltrate into the area of the thymic carcinoma. There was probably no direct relationship between the occurrence of thymic carcinoma and T lymphoblastic leukemia/lymphoma, but they may have both arisen coincidentally in association with thymoma. In summary, we report a case of concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma presenting as an anterior mediastinal mass. Thymoma and T lymphoblastic leukemia/lymphoma can combine in the same mass, although this is quite rare. T lymphoblastic leukemia/lymphoma resembles the activated immature non-neoplastic lymphocytes of thymoma in
Please cite this article in press as: J. Ito, et al., Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass, Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.06.002
G Model PRP-51409; No. of Pages 4
ARTICLE IN PRESS
4
J. Ito et al. / Pathology – Research and Practice xxx (2015) xxx–xxx
Fig. 3. In the background of the thymoma, atypical lymphoid component was identified. (A) The atypical lymphocytes showed medium-sized, irregular-shaped nuclei with condensed chromatin (HE, 400×). These cells were positive for TdT (inset). (B) Atypical lymphocytes infiltrated into the left lung (b: HE, 40×). (C) Infiltrating atypical lymphocytes in the lung were not accompanied by thymic epithelial cells (AE1/AE3, 200×). (D) Lymphoblasts represented 83% of the bone marrow (HE, 200×).
terms of their morphology and immunophenotype. Therefore, the presence of T lymphoblastic leukemia/lymphoma in the thymoma can be misinterpreted as non-neoplastic lymphocytes. However, T lymphoblastic leukemia/lymphoma cells have larger and more irregular nuclei, with condensed chromatin, in comparison with non-neoplastic lymphocytes. At the time of the diagnosis of thymoma, additional attention should be directed toward lymphocytes in the background. When the lymphocytes in the thymoma have atypia which cannot be considered as activated immature non-neoplastic lymphocytes, molecular genetic analysis should be considered to rule out the possibility of concurrent T lymphoblastic leukemia/lymphoma. References [1] V. Ertel, M. Fruh, A. Guenther, T. Cerny, C. Fretz, S. Cogliatti, Thymoma with molecularly verified “conversion” to T lymphoblastic leukemia/lymphoma over 9 years, Leuk. Lymphoma 54 (2013) 2765–2768. [2] H.D. Friedman, D.A. Inman, R.E. Hutchison, B.J. Poiesz, Concurrent invasive thymoma and T-cell lymphoblastic leukemia and lymphoma. A case report with necropsy findings and literature review of thymoma and associated hematologic neoplasm, Am. J. Clin. Pathol. 101 (1994) 432–437.
[3] T.S. Gould, P.R. Tanguay, R. Delellis, Thymoma and primary lymphoma of the small intestine, Cancer 40 (1977) 1755–1758. [4] W.R. Macon, T.H. Rynalski, S.H. Swerdlow, J.B. Cousar, T-cell lymphoblastic leukemia/lymphoma presenting in a recurrent thymoma, Mod. Pathol. 4 (1991) 524–528. [5] L.F. Skinnider, S. Alexander, D. Horsman, Concurrent thymoma and lymphoma: a report of two cases, Hum. Pathol. 13 (1982) 163–166. [6] F. Rovera, P. Billo, C. Capella, L. Dominioni, Concurrent epithelial thymoma and T-cell lymphoblastic lymphoma, Interact. Cardiovasc. Thorac. Surg. 2 (2003) 537–540. [7] R. Nishioka, S. Nakajima, Y. Morimoto, H. Suzuki, H. Nakamura, M. Suzuki, T-cell acute lymphoblastic leukemia with transient pure red cell aplasia associated with myasthenia gravis and invasive thymoma, Intern. Med. 34 (1995) 127–130. [8] J.V. Souadjian, P. Enriquez, M.N. Silverstein, J.M. Pepin, The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch. Intern. Med. 134 (1974) 374–379. [9] G.P. Smith, S.L. Perkins, G.H. Segal, C.R. Kjeldsberg, T-cell lymphocytosis associated with invasive thymomas, Am. J. Clin. Pathol. 102 (1994) 447–453. [10] A.D. Barton, T-cell lymphocytosis associated with lymphocyte-rich thymoma, Cancer 80 (1997) 1409–1417. [11] T.T. Kuo, J.K. Chan, Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile, Am. J. Surg. Pathol. 22 (1998) 1474–1481. [12] S. Suster, C.A. Moran, Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases, Am. J. Surg. Pathol. 20 (1996) 1469–1480.
Please cite this article in press as: J. Ito, et al., Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass, Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.06.002
ARTICLE IN PRESS Pathology – Research and Practice xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Pathology – Research and Practice journal homepage: www.elsevier.com/locate/prp
Teaching cases
Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass Junko Ito a , Akihiko Yoshida a , Akiko Miyagi Maeshima a , Kazuo Nakagawa b , Shun-ichi Watanabe b , Yukio Kobayashi c , Suguru Fukuhara c , Koji Tsuta a,∗ a
Division of Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo 104-0045, Japan c Department of Hematology, National Cancer Center Hospital, Tokyo 104-0045, Japan b
a r t i c l e
i n f o
Article history: Received 25 March 2015 Received in revised form 17 May 2015 Accepted 5 June 2015 Keywords: Thymus Thymoma T lymphoblastic leukemia/lymphoma Thymic carcinoma
a b s t r a c t We report a case of a 62-year-old man with concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma. Computed tomography revealed a 5.5-cm anterior mediastinal mass, and surgical resection was performed. Histologically, the mass showed concurrent thymoma (type AB), thymic carcinoma, and T lymphoblastic leukemia/lymphoma. Lymphoma cells infiltrated in the left lung, pulmonary hilar lymph nodes, and involved bone marrow. The patient underwent chemotherapy for T lymphoblastic leukemia/lymphoma and achieved remission. One year after surgery, he remains free of both thymoma and thymic carcinoma, and T lymphoblastic leukemia/lymphoma remains complete remission under maintenance therapy. Thymoma and T lymphoblastic leukemia/lymphoma can combine in the same mass, although this is quite rare. At the time of the diagnosis of thymoma, additional attention should be directed toward lymphocytes in the background. © 2015 Elsevier GmbH. All rights reserved.
1. Introduction Thymoma is a neoplasm that originates from thymic epithelial cells and is frequently associated with mature or immature non-neoplastic lymphocytes. On the other hand, T lymphoblastic leukemia/lymphoma is a neoplasm of lymphoblasts committed to the T-cell lineage, and it frequently shows mediastinal involvement. The distinction between thymoma and T lymphoblastic leukemia/lymphoma is occasionally difficult, because the immature lymphocytes associated with thymoma may resemble T lymphoblastic leukemia/lymphoma cells, both morphologically and immunohistochemically. Here, we report an extraordinary case of concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma presenting as an anterior mediastinal mass.
mass in the left anterior mediastinum. Surgical resection for the mass was performed in addition to the lobectomy of the left upper lobe of the lung; pulmonary hilar lymph nodes were also dissected. On post-operative day 6, the platelet counts decreased markedly (from 314,000/l before surgery to 77,000/l on day 6). Because the possibility of hematologic malignancy could not be excluded as the cause of the thrombocytopenia, bone marrow aspiration was performed from the ilium, which lead to the diagnosis of T lymphoblastic leukemia/lymphoma. There were no blast cells in the peripheral blood. The patient underwent chemotherapy for T lymphoblastic leukemia/lymphoma, and achieved remission. One year after surgery, he remains free of both thymoma and thymic carcinoma, and T lymphoblastic leukemia/lymphoma remains in complete remission under maintenance therapy. Informed consent was obtained from the patient for publication of this case report.
2. Clinical history A 62-year-old man complained of fever and chest pain. Computed tomography (CT) scan of the chest demonstrated a 5.5-cm
∗ Corresponding author at: The Division of Pathology, National Cancer Center Hospital, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. Tel.: +81 3 3542 2511; fax: +81 3 3545 3567. E-mail address: [email protected] (K. Tsuta).
3. Pathological findings Grossly, the resected specimen showed a multinodular tumor in the anterior mediastinum, measuring 9.2 cm × 5.7 cm × 5.2 cm. The cut surface of the tumor was multiple tan-colored nodules with fibrosis and necrosis (Fig. 1). The tumor was encapsulated, but the demarcation from the lung and fat tissue was partly ill-defined.
http://dx.doi.org/10.1016/j.prp.2015.06.002 0344-0338/© 2015 Elsevier GmbH. All rights reserved.
Please cite this article in press as: J. Ito, et al., Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass, Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.06.002
G Model PRP-51409; No. of Pages 4
ARTICLE IN PRESS
2
J. Ito et al. / Pathology – Research and Practice xxx (2015) xxx–xxx
Fig. 1. The gross cut surface of the tumor showed multiple tan-colored nodules with fibrosis and necrosis. In inset, the components of thymoma and thymic carcinoma were shown with white and red, respectively. The rest of the tumor consisted of fibrosis and necrosis, which was shown with green oblique lines. The capsule of the thymoma was indicated with black line. The infiltration of T lymphoblastic leukemia/lymphoma cells was shown with blue dots. (For interpretation of the references to color in figure legend, the reader is referred to the web version of the article.)
Histologically, approximately 30% of the mediastinal tumor showed features of type AB thymoma, consisting of a mixture of lymphocyte-poor type A thymoma component and lymphocyterich type B thymoma-like component. Type A thymoma component showed diffuse growth of short spindle cells with focal rosettelike structures and a few mature lymphocytes (Fig. 2A and B). Type B thymoma-like component showed scattered polygonal or round epithelial cells in a prominent population of lymphocytes (Fig. 2C). The epithelial tumor cells were immunopositive for AE1/AE3 cytokeratins (Fig. 2D), p40, and focally positive for CD20. Foci of microinvasion into perithymic adipose tissue and left lung parenchyma were noted. In addition to the above thymoma morphology, multiple nests of malignant component were noted, in which pleomorphic cells proliferated (Fig. 2E and F). These areas were poorly differentiated thymic squamous cell carcinomas, and the diagnosis was immunohistochemically supported by focal positivity to CD5 and p40. The thymic carcinoma component accounted for approximately 5% of the mediastinal tumor. The rest of the tumor consisted of fibrosis and necrosis. We also noted a mix of atypical lymphocytes and small nonatypical lymphocytes in the background of the thymoma. The atypical lymphocytes showed medium-sized, irregular-shaped nuclei with condensed chromatin and mitotic activity (Fig. 3A). These cells infiltrated into the left lung and the pulmonary hilar lymph nodes without accompanying epithelial tumor cells (Fig. 3B and C). Both atypical and non-atypical lymphocytes were positive for TdT (Fig. 3A inset), CD1a, CD99, CD5, CD3, CD7, CD4, and CD8, but they were negative for CD20. Clonal rearrangement of the T-cell receptor  chain gene was identified from the atypical lymphocytes by polymerase chain reaction (PCR), and these cells were diagnosed as T lymphoblastic leukemia/lymphoma. T lymphoblastic leukemia/lymphoma cells accounted for approximately 70% of the lymphocytes in the background of the thymoma, and infiltrated
into the adjacent left lung and the pulmonary hilar lymph nodes. Bone marrow aspiration revealed that lymphoblasts represented 83% of the bone marrow (Fig. 3D). 4. Discussion Both thymoma and T lymphoblastic leukemia/lymphoma arise in mediastinum, and the immature lymphocytes associated with thymoma may resemble T lymphoblastic leukemia/lymphoma cells. Therefore, it is occasionally difficult to distinguish these two lesions. The presence of neoplastic epithelial cells in thymoma is the important clue for distinguishing thymoma from T lymphoblastic leukemia/lymphoma. In our case, epithelial cells were diffusely present in the mediastinal mass, but only atypical lymphocytes infiltrated into the lung, lymph nodes, and bone marrow without epithelial cells. Furthermore, molecular genetic analyses revealed clonal rearrangement of the T-cell receptor  chain gene. These findings altogether helped us make definitive diagnosis of concurrent thymoma and T lymphoblastic leukemia/lymphoma. Concurrent thymoma and malignant leukemia/lymphoma is rare [1–7], and only two reports have previously described the coexistence of thymoma and T lymphoblastic leukemia/lymphoma in the same lesion [4,6]. Although the pathogenesis of concurrent thymoma and T lymphoblastic leukemia/lymphoma is still unclear, two theories are conceivable. First, lymphocytes in the thymoma may have transformed into T lymphoblastic leukemia/lymphoma [1,4,7,8]. Second, T lymphoblastic leukemia/lymphoma may have occurred coincidentally, and infiltrated into the thymoma [7]. The neoplastic epithelial cells of thymoma may retain the function of attracting immature T cells, akin to the normal thymus. In some previously reported cases, malignant lymphoma/leukemia arose after chemotherapy or radiation therapy for thymoma, and some authors have discussed the possibility of secondary malignant lymphoma
Please cite this article in press as: J. Ito, et al., Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass, Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.06.002
G Model PRP-51409; No. of Pages 4
ARTICLE IN PRESS J. Ito et al. / Pathology – Research and Practice xxx (2015) xxx–xxx
3
Fig. 2. Histological findings of the type AB thymoma and thymic carcinoma. (A) Type A thymoma component showed diffuse growth of short spindle cells with a few mature lymphocytes (HE, 200×). (B) The tumor cells partly formed rosette-like structures in the type A thymoma component (HE, 200×). (C) Type B thymoma-like component showed scattered polygonal or round epithelial cells in a prominent population of lymphocytes (HE, 200×). (D) The epithelial tumor cells were positive for AE1/AE3 cytokeratins (200×). (E) The nests of the thymic carcinoma (left side) were adjacent to thymoma (right side) (HE, 100×). (F) High-power view of the thymic carcinoma showed pleomorphic malignant cells arranged in the nest. Mitotic figures were frequently encountered (HE, 200×).
that is triggered by thymoma treatment [4,7]. However, our patient did not receive any treatment before surgery. In the present case, the possibility of T-cell lymphocytosis was initially considered. This is a phenomenon in which polyclonal, non-neoplastic T cells proliferate in peripheral blood, bone marrow and other parenchymal organs, usually associated with lymphocyte-rich and invasive thymoma. Although this phenomenon is very rare, a few cases have been reported [9,10]. However, this is not applicable to our case because we observed clonal rearrangement of the T-cell receptor  chain gene. In addition to thymoma and T lymphoblastic leukemia/ lymphoma, thymic carcinoma was also present in our case. On rare occasions, thymoma can undergo malignant transformation into
thymic carcinoma [11,12]. However, the literature does not include any reports of the coexistence of thymic carcinoma and malignant lymphoma. In our patient, T lymphoblastic leukemia/lymphoma did not infiltrate into the area of the thymic carcinoma. There was probably no direct relationship between the occurrence of thymic carcinoma and T lymphoblastic leukemia/lymphoma, but they may have both arisen coincidentally in association with thymoma. In summary, we report a case of concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma presenting as an anterior mediastinal mass. Thymoma and T lymphoblastic leukemia/lymphoma can combine in the same mass, although this is quite rare. T lymphoblastic leukemia/lymphoma resembles the activated immature non-neoplastic lymphocytes of thymoma in
Please cite this article in press as: J. Ito, et al., Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass, Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.06.002
G Model PRP-51409; No. of Pages 4
ARTICLE IN PRESS
4
J. Ito et al. / Pathology – Research and Practice xxx (2015) xxx–xxx
Fig. 3. In the background of the thymoma, atypical lymphoid component was identified. (A) The atypical lymphocytes showed medium-sized, irregular-shaped nuclei with condensed chromatin (HE, 400×). These cells were positive for TdT (inset). (B) Atypical lymphocytes infiltrated into the left lung (b: HE, 40×). (C) Infiltrating atypical lymphocytes in the lung were not accompanied by thymic epithelial cells (AE1/AE3, 200×). (D) Lymphoblasts represented 83% of the bone marrow (HE, 200×).
terms of their morphology and immunophenotype. Therefore, the presence of T lymphoblastic leukemia/lymphoma in the thymoma can be misinterpreted as non-neoplastic lymphocytes. However, T lymphoblastic leukemia/lymphoma cells have larger and more irregular nuclei, with condensed chromatin, in comparison with non-neoplastic lymphocytes. At the time of the diagnosis of thymoma, additional attention should be directed toward lymphocytes in the background. When the lymphocytes in the thymoma have atypia which cannot be considered as activated immature non-neoplastic lymphocytes, molecular genetic analysis should be considered to rule out the possibility of concurrent T lymphoblastic leukemia/lymphoma. References [1] V. Ertel, M. Fruh, A. Guenther, T. Cerny, C. Fretz, S. Cogliatti, Thymoma with molecularly verified “conversion” to T lymphoblastic leukemia/lymphoma over 9 years, Leuk. Lymphoma 54 (2013) 2765–2768. [2] H.D. Friedman, D.A. Inman, R.E. Hutchison, B.J. Poiesz, Concurrent invasive thymoma and T-cell lymphoblastic leukemia and lymphoma. A case report with necropsy findings and literature review of thymoma and associated hematologic neoplasm, Am. J. Clin. Pathol. 101 (1994) 432–437.
[3] T.S. Gould, P.R. Tanguay, R. Delellis, Thymoma and primary lymphoma of the small intestine, Cancer 40 (1977) 1755–1758. [4] W.R. Macon, T.H. Rynalski, S.H. Swerdlow, J.B. Cousar, T-cell lymphoblastic leukemia/lymphoma presenting in a recurrent thymoma, Mod. Pathol. 4 (1991) 524–528. [5] L.F. Skinnider, S. Alexander, D. Horsman, Concurrent thymoma and lymphoma: a report of two cases, Hum. Pathol. 13 (1982) 163–166. [6] F. Rovera, P. Billo, C. Capella, L. Dominioni, Concurrent epithelial thymoma and T-cell lymphoblastic lymphoma, Interact. Cardiovasc. Thorac. Surg. 2 (2003) 537–540. [7] R. Nishioka, S. Nakajima, Y. Morimoto, H. Suzuki, H. Nakamura, M. Suzuki, T-cell acute lymphoblastic leukemia with transient pure red cell aplasia associated with myasthenia gravis and invasive thymoma, Intern. Med. 34 (1995) 127–130. [8] J.V. Souadjian, P. Enriquez, M.N. Silverstein, J.M. Pepin, The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch. Intern. Med. 134 (1974) 374–379. [9] G.P. Smith, S.L. Perkins, G.H. Segal, C.R. Kjeldsberg, T-cell lymphocytosis associated with invasive thymomas, Am. J. Clin. Pathol. 102 (1994) 447–453. [10] A.D. Barton, T-cell lymphocytosis associated with lymphocyte-rich thymoma, Cancer 80 (1997) 1409–1417. [11] T.T. Kuo, J.K. Chan, Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile, Am. J. Surg. Pathol. 22 (1998) 1474–1481. [12] S. Suster, C.A. Moran, Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases, Am. J. Surg. Pathol. 20 (1996) 1469–1480.
Please cite this article in press as: J. Ito, et al., Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass, Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.06.002
