Type AB thymoma accompanied by pure red cell aplasia and Good syndrome with CMV infection of tumor cells

Reported herein is a case of type AB thymoma accompanied by pure red cell aplasia (PRCA) and Good syndrome. The patient was a 55-year-old woman who was found to be anemic and to have an abnormal shadow at the left pulmonary hilus on routine medical examination. Bone marrow aspiration was performed and she was diagnosed as having PRCA. She also had hypogammaglobulinemia. The anemia was temporarily cured with oral prednisolone and cyclosporin A, and the patient underwent total thymectomy. The tumor was type AB thymoma, composed mainly of type A components; widespread spindle cell components showed slight to moderate infiltration of immature T-cells. In addition, CMV inclusion bodies were scattered throughout this tumor. The CMV-infected cells were tumor cells, because they were positive for pancytokeratin and negative for CD34. Several cases of Good syndrome with widespread CMV infection have been reported, but it is extremely rare for CMV-inclusion bodies to be found in tumor cells. No thymoma cases involving CMV infection of tumor cells have been reported.     

Severe T- and B-cell immune deficiency associated with malignant thymoma.

BACKGROUND: Immunodeficiency with thymoma syndrome is a rare disorder that generally occurs after the fourth decade of life. Typically, thymic tumors are benign, and gradually developing immunodeficiency consists of hypogammaglobulinemia with low B-cell counts and an inverted CD4+/CD8+ T-cell ratio due to excessive CD8+ T cells. OBJECTIVE: To report the case of a 32-year-old, white man with an invasive malignant thymoma and profound combined T- and B-cell immunodeficiency associated with a normal CD4+/CD8+ T-cell ratio, absence of circulating B cells, and infection with an unusual organism. METHODS: The patient presented with a superior vena cava syndrome caused by a malignant thymoma. During chemotherapy and radiotherapy, he experienced recurrent episodes of pulmonary infections due to Haemophilus influenza and Serratia marcescens and persistent oral thrush. He was diagnosed as having thymoma and underwent immunological evaluation. RESULTS: Sixteen months after the diagnosis of thymoma, the immunological evaluation revealed profound lymphopenia, eosinopenia, very low counts of both CD4+ T cells and CD8+ T cells, and a normal CD4+/CD8+ ratio with negative delayed-type hypersensitivity skin test results. Hypogammaglobulinemia and absent specific antibody responses were associated with a lack of peripheral blood CD19+ B cells. Despite treatment with intravenous immunoglobulin, the patient died of respiratory insufficiency and sepsis secondary to a chronic pulmonary infection. CONCLUSIONS: Malignant thymoma may be associated with severe combined immunodeficiency. A normal CD4+/CD8+ ratio and the absence of peripheral B cells suggest a bone marrow defect that affects both T and B cells in the pathogenesis of this syndrome. Comprehensive immunological evaluation should be performed when thymoma is diagnosed to initiate an early and effective treatment to prevent life-threatening complications.     

Clonality analysis performed using human androgen receptor assay in a rare case of undifferentiated thymic carcinoma coexisting with type AB thymoma

We report a very rare case of combined thymic carcinomas: undifferentiated thymic carcinoma coexisting with type AB thymoma. The precise mechanism underlying the coexistence of these tumors remains unknown. Therefore, we used clonality analysis to ascertain whether the two tumors were clonally related. A 63‐year‐old woman with thyroid cancer visited our hospital. Chest computed tomography also revealed an anterior mediastinal tumor. The patient was treated with total thyroidectomy and surgery for mediastinal tumors together with left upper lobe partial resection. The mediastinal tumor was pathologically diagnosed as undifferentiated thymic carcinoma coexisting with type AB thymoma. Multiple pulmonary metastases were detected in the patient and stage IV disease was diagnosed. The tumor was treatment‐resistant, and the patient received fourth‐line chemotherapy. We conducted clonality analysis using an improved human androgen receptor gene‐amplification assay that involves random X‐chromosome inactivation through methylation, followed by methylated gene‐specific PCR amplification after sample DNA digestion with HpaII, a methylation‐sensitive restriction enzyme. Clonality analysis demonstrated identical X‐chromosome inactivation in cells present in both thymoma and thymic carcinoma areas, and thus revealed clonal proliferation. The two lesions in the patient might have arisen through the transformation of a preexisting thymoma into a more malignant lesion.     

Treatment of acute myeloid leukaemia in a renal allograft recipient: implications of cyclosporin immunosuppressive treatment.

The clinical effects of cyclosporin were evaluated during cytotoxic treatment in a 61 year old man with acute myeloid leukaemia. He had required a renal transplant 18 months before presenting with acute myeloid leukaemia (FAB subtype M4). He had received cyclosporin 3.5-4.0 mg/kg daily to maintain a plasma cyclosporin concentration of 75-150 ng/ml. Cyclosporin was continued during induction chemotherapy with daunorubicin, cytarabine, and 6-thioguanine (DAT). He had fever and oropharyngeal candidiasis that was unresponsive to anti-bacterial drugs but responsive to systemic amphotericin. Bone marrow examination 14 days after chemotherapy showed complete haematological remission. Subsequently he tolerated consolidation treatment with DAT with no serious complications. Unfortunately he developed fatal septicaemia following a second consolidation with mitozantrone and cytarabine. Inhibition of P-glycoprotein activity by cyclosporin may not significantly increase the toxicity of aggressive chemotherapeutic regimens, and as benefit may be achieved by this approach further clinical evaluation is justified.     

T-cell lymphoblastic leukemia/lymphoma presenting in a recurrent thymoma

A lymphoblastic malignancy presented as the lymphoid component of a recurrent invasive lymphocyte-rich thymoma that had been previously resected and treated with chemotherapy. This high grade lymphoid neoplasm concurrently involved mediastinal nodes and subsequently disseminated to pleural fluid and peripheral blood. Lymphocytes with convoluted nuclei demonstrated a T-lymphoblastic phenotype (UCHL1+, Leu-22+, TdT+) by immunohistochemical studies. T-cell lymphoblastic leukemia/lymphomas in this clinical setting have not been reported, and this case suggests that neoplastic transformation of lymphocytes may occur in longstanding refractory thymomas.     

Degree of malignancy of thymic epithelial tumors in terms of nuclear DNA content and nuclear area. An analysis of 39 cases.

For determination of the degree of malignancy among thymic epithelial tumors, the DNA content and area of nuclei in 13 cases each of noninvasive thymoma, invasive thymoma, and thymic carcinoma were investigated by cytofluorometry and morphometry. The nuclear DNA content was determined in terms of the mean nuclear DNA content, DNA histogram pattern, and the occurrence of the aneuploid stem cell line. The mean nuclear DNA content of the thymic carcinoma was significantly higher than that of both subgroups of thymoma (P less than 0.01), but there was no significant difference between noninvasive and invasive thymomas. The aneuploid stem cell line appeared in 92.3% of thymic carcinomas, one case (7.7%) of invasive thymomas, and none of noninvasive thymomas. Abnormal DNA histogram patterns were seen in 53.8% of thymic carcinomas and none of the thymomas. The mean nuclear area increased significantly in the increasing order of noninvasive thymoma, invasive thymoma, and thymic carcinoma (P less than 0.01). The cytofluorometric and morphometric results demonstrated a significant difference in degree of malignancy between thymic carcinoma and thymoma; however, there was a trend toward an increasing degree of malignancy from noninvasive to invasive thymomas, yet there was a sizeable overlap in results between the two groups. Therefore, these two methods are not satisfactory for predicting the behavior of an individual case of noninvasive or invasive thymoma.     

侵袭性与非侵袭性胸腺瘤的影像特征及临床分型特点

目的 分析侵袭性与非侵袭性胸腺瘤的影像特征及临床分型分期、鉴别诊断。方法 选取2013年1月~2018年12月我院经术后病理证实的胸腺瘤患者25例,根据2015年WHO胸腺瘤诊断标准及Masaoka临床分期及对胸腺瘤进行侵袭性和非侵袭性分组,并对胸腺瘤的CT/MR表现与临床分型分期进行分析。结果 共25例胸腺瘤患者,其中非侵袭性13例,侵袭性12例。侵袭性胸腺瘤CT表现:肿瘤位置为基本中央型1例、左偏型6例、右偏型5例;肿瘤形态为浅分叶形4例、不规则形8例;肿块周围脂肪间隙为狭窄6例、消失4例、模糊2例;肿瘤无钙化6例、钙化6例;肿瘤包膜完整3例、不完整9例。非侵袭性胸腺瘤CT表现:肿瘤位置为基本中央型3例、左偏型3例、右偏型7例;肿瘤形态为类圆形8例,浅分叶形5例;肿块周围脂肪间隙清晰存在13例;肿瘤无钙化9例,边缘钙化4例;肿瘤包膜完整13例。6例侵袭性胸腺瘤MR表现为等T1WI、长/稍长T2WI信号。结论 侵袭性与非侵袭性胸腺瘤各自有一定的影像特征,且与临床分型、分期可能存在联系,根据其影像表现并结合临床症状,可准确鉴别其是否为侵袭性。     

Polypoid endobronchial extension from invasive thymoma

Summary A case of invasive thymoma which was manifest clinically as bronchial obstruction and metastatic liver tumour is presented. Autopsy revealed a unique polypoid endobronchial extension of the neoplasm. This represents a previously unrecognized pattern of secondary bronchial involvement by invasive thymoma.     

Cytologic patterns of metastatic thymoma: Diagnosis by fine-needle aspiration biopsy

Thymomas are the most frequent primary tumors of the anterior mediastinum. These lesions are slow growing and can be locally invasive, but extrathoracic metastases are rare, occurring in less than 2% of cases. Fine-needle aspiration biopsy (FNAB) may be helpful in making the diagnosis of metastatic thymoma, with or without a clinical history of primary mediastinal thymoma. We report three cases of metastatic thymoma diagnosed by FNAB. Each case illustrates a distinctive cytologic pattern. While two of the patients had a history of histologically confirmed thymoma 11 and 13 years previously, a third patient presented with an enlarged supraclavicular lymph node and pulmonary nodules, and no prior diagnosis of thymoma. These cases demonstrate that based on distinctive cytologic patterns and features, a diagnosis of metastatic thymoma can be made with FNAB. Ancillary studies will often confirm the diagnosis. Diagn Cytopathol 1994;11:182–187. © 1994 Wiley-Liss, Inc.     

Intracaval and intracardiac extension of invasive thymoma complicated by superior and inferior vena cava syndrome

We present a case of an aged male with invasive thymoma that extended into the right atrium and led to superior and inferior vena cava syndrome. The patient initially presented with edema of the face and bilateral lower extremities. Echocardiography revealed a mass within the right atrium. Imaging studies demonstrated an anterior mediastinal tumor that continuously occupied the bilateral brachiocephalic veins, superior vena cava, and right atrium. Pathological diagnosis of the tumor biopsy was highly suspicious of thymoma. Due to the high risk of wide spread of the tumor, treatments including resection of the tumor were impossible. Several days later he died, and an autopsy was performed. The tumor was type B2 thymoma invading bilateral brachiocephalic veins, superior vena cava and right atrium. Multiple tumor emboli within the pulmonary arteries were identified. Direct cause of death was deemed to be tumor strangulation at the tricuspid orifice. In addition to the superior vena cava syndrome, inferior vena cava syndrome including ectasia of the intrahepatic vessels was confirmed along with pericarditis. To our knowledge, this is the first English report of an autopsy case of intracardiac thymoma extension, and a detailed literature review of similar cases is also presented.     

Malignant germ cell tumor of the anterior mediastinum with leukemia-like infiltration

We present here a rare autopsy case of malignant germ cell tumor with leukemia-like infiltration of the anterior mediastinum in a 35-year-old male. Chest X-rays revealed an abnormal mediastinum, which was diagnosed as thymoma. During the course of treatment, huge abnormal cells 40-50 mu in size were found in the peripheral blood smear and disseminated bone metastasis of the malignant thymoma was suspected. The tumor was resistant to both chemotherapy and radiotherapy. The patient died of respiratory failure. The autopsy disclosed a huge tumor measuring 24 X 13 X 10 cm in the anterior mediastinum. Histological findings of the tumor revealed cells which had spread to almost all organs, indicating leukemia-like infiltration. This pattern of metastasis has been reported in the cancer of non-hematologic origin under the term "carcinocythemia (CCA)". To our knowledge, the present case is the first report of a leukemia-like infiltration in case of malignant germ cell tumor. Careful serial section revealed no primary foci in either testis.     

Clinical and laboratory features of seventy-eight UK patients with Good’s syndrome (thymoma and hypogammaglobulinaemia)

Good’s syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were female, were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and nine (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were significantly lower in these patients with malignant thymoma. Seventy-four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren’s syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good’s syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinaemia.     

全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤30例

目的：探讨全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤的临床价值。方法：回顾性分析30例经全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤患者的临床资料,总结其手术方法、分期、病理学类型、后续治疗、并发症、随访结果等。结果：30例患者全部经右侧胸腔镜完成胸腺切除术,其中男性12例、女性18例,无中转开胸,无围手术期死亡和严重并发症;手术时间40—200min,平均（91．7±38．1）min,出血量30～300ml,平均（106±75）ml;术后住院时间5—7d,平均（5．1±0．8）d。术后临床分期,I期17例（56．7％）、II期13例（43．3％）。病理学类型,A型14例、AB型10例、B1型5例、B2型1例。Ⅱ期患者术后均接受辅助放疗。患者全部随访,随访时间6—72个月,中位随访时间44个月。随访期内无一例复发或死亡,总生存率（OS）为（70．2±1．7）个月（95％CI：66．8—73．6）。结论：全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤安全、有效,而且更加微创,值得临床推广应用。     

Invasive thymoma with paraneoplastic retinopathy

A 60-year-old man was admitted for progressive visual loss in both eyes. He was diagnosed with retinopathy and chest computed tomography revealed an invasive thymoma. In western blot analysis, serum autoantibodies against recoverin, photoreceptor-specific calcium-binding protein, and heat shock cognate protein 70 which were identified as the cause of cancer-associated retinopathy (CAR). Immunofluorescence staining showed that thymoma cells also expressed recoverin. These observations strongly suggested that similar pathogenesis of CAR was involved in the presented case.     

Needle tract implantation of thymoma after transthoracic needle biopsy.

A 73 year old woman was admitted to hospital because of an anterior mediastinal mass. For definite diagnosis, needle biopsy was performed under fluoroscopic observation. The histopathological diagnosis was thymoma and combination chemotherapy was given. The tumour almost completely disappeared and the patient was discharged. But the tumour recurred in the left anterior chest wall four months later. It is suggested that the thymoma tissue had been implanted in the needle tract.     

MALIGNANT GERM CELL TUMOR OF THE ANTERIOR MEDIASTINUM WITH LEUKEMIA-LIKE INFILTRATION

We present here a rare autopsy case of malignant germ cell tumor with leukemia-like infiltration of the anterior mediastinum in a 35-year-old male. Chest X-rays revealed an abnormal mediastinum, which was diagnosed as thymoma. During the course of treatment, huge abnormal cells 40–50 μ in size were found in the peripheral blood smear and disseminated bone metastasis of the malignant thymoma was suspected. The tumor was resistant to both chemotherapy and radiotherapy. The patient died of respiratory failure. The autopsy disclosed a huge tumor measuring 24x13x10 cm in the anterior mediastinum. Histological findings of the tumor revealed cells which had spread to almost all organs, indicating leukemia-like infiltration. This pattern of metastasis has been reported in the cancer of non-hematologic origin under the term "carcinocythemia (CCA)". To our knowledge, the present case is the first report of a leukemia-like infiltration in case of malignant germ cell tumor. Careful serial section revealed no primary foci in either testis. ACTA PATH-OL. JPN. 35: 1561–1570, 1985.     

Cutaneous infection caused by Cylindrocarpon lichenicola in a patient with acute myelogenous leukemia

Cylindrocarpon lichenicola is a saprophytic soil fungus which has rarely been associated with human disease. We report the first case of localized invasive cutaneous infection caused by this fungus in a 53-year-old male from the rural midwestern United States with relapsed acute myelogenous leukemia. On admission for induction chemotherapy, the patient was noted to have an abrasive laceration between the fourth and fifth metacarpophalangeal joints and on the dorsum of the right hand, which progressed to frank ulceration following chemotherapy. A biopsy provided an initial diagnosis of an invasive fungal infection consistent with aspergillosis based on the histopathological appearance of the mold in tissue. Multiple positive fungal cultures which were obtained from the biopsied tissue were subsequently identified by microscopic and macroscopic characteristics to be C. lichenicola. The infection resolved following marrow regeneration, aggressive debridement of the affected tissue, and treatment with amphotericin B. This case extends the conditions associated with invasive disease caused by C. lichenicola.     

Clinicopathological features of type AB thymoma with liver metastases

Objective: We studied the clinicopathological features of type AB thymoma with liver metastases and explore the histological types, diagnosis and differential diagnosis, treatment and prognosis for this disease. Methods: Liver metastasis specimens were derived from one case of type AB thymoma 5 years after operation and were examined histologically using light microscopy and immunohistochemistry. A comprehensive analysis was performed on the patient’s clinical manifestations, histopathology, immunohistochemistry features, differential diagnosis, treatment and prognosis in combination with a review of the relevant literature. Results: Metastases were detected 5 years after initial operation on a 49-year-old, female patient with type AB thymoma. The pathological diagnosis for the liver metastases was type AB thymoma. Immunohistochemistry staining showed CKpan (+), CD3 (+), CD2 (+), TdT (+), CD5 (+), P53 (+), Hep-1 (-), and Ki67-positive cells (25%). The expression level of galectin-3 was higher than in the mediastinal thymoma tissue identified 5 years prior. Conclusion: Liver metastases of type AB thymoma are extremely rare. This case indicated that type AB thymoma with low malignant potential might recur and develop distant metastases. Overexpression of p53, galectin-3 and Ki67 in type AB thymoma might coordinately manipulate the process of development, progression and malignant transformation of type AB thymomas.     

Thymoma presenting as a superior vena cava syndrome remission following therapy

Summary A 45-year-old male developed myasthenia gravis 8 years ago. He received prednisone for 3 years, and resumed complete clinical remission. Five years later, he was admitted with obstruction of the superior vena cava. Invasive thymoma was diagnosed by chest X-ray and an open lung biopsy. Radiation followed by combination chemotherapy with cyclophosphamide, vincristine, and prednisone induced a complete remission. The patient remained disease-free for more than 20 months after the first admission to our department. To the best of our knowledge, superior vena cava syndrome as the presenting symptom of thymoma has never been reported previously.     

Hodgkin's disease accompanied with thymoma

An autopsy case of Hodgkin's disease accompanied with thymoma is reported. The patient died of acute interstitial pneumonitis 9 years after the development of lymphadenopathy. On post-mortem examination thymoma was recognized. We believe that the present case is a very rare Hodgkin's disease complicating thymoma. The occurrence of second neoplasia in Hodgkin's disease is also discussed.