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30 December 2024: Articles  Japan

B-Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma Mimicking Fibrosing Mediastinitis: A Case Report and Diagnostic Insight

Unknown etiology, Challenging differential diagnosis, Unusual or unexpected effect of treatment

Aya Kitamura1ABCDEF, Shigehisa Yanagi1ABCDEFG*, Kotaro Shide ORCID logo2ABCDEF, Yuichiro Sato3ABCDE, Ayako Kamiunten2BDE, Yasuhiro Yamanari1BE, Akiko Kitamura1E, Makoto Sumiyoshi1E, Yasuharu Oda ORCID logo1E, Hironobu Tsubouchi1E, Kazuya Shimoda2ADEF, Taiga Miyazaki1ADEF

DOI: 10.12659/AJCR.945804

Am J Case Rep 2024; 25:e945804

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Abstract

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BACKGROUND: Fibrosing mediastinitis (FM) is a rare, fibroproliferative disorder within the mediastinum. It is extremely rare for hematologic malignancies to develop as FM.

CASE REPORT: A 32-year-old Japanese man with a 1-month history of headache and 2-week history of facial swelling underwent chest computed tomography (CT); a diffuse mass-like lesion was revealed in the anterior mediastinum with severe stenosis of vital mediastinal organs. After a surgical biopsy, an initial diagnosis of idiopathic FM was made. The FM lesions responded mildly to corticosteroids but recurred repeatedly. Sixteen months after the treatment initiation, blasts appeared in the peripheral blood (PB), and the patient was diagnosed with B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL). Chemotherapy led to complete remission of the B-ALL/LBL and almost complete disappearance of FM-like lesions. Immunohistochemistry of the mediastinal biopsy specimen taken before the blasts’ appearance in PB demonstrated a CD34/CD7/terminal deoxynucleotidyl transferase-positive population, an identical pattern of expression common to the blasts in the patient’s PB and bone marrow.

CONCLUSIONS: This is the first case report of B-ALL/LBL presenting as FM. This case underscores the importance of considering the possibility of latent hematologic malignancy even in the absence of new symptoms other than those caused by FM lesions for a long period of time. This is the first demonstration that leukemia cells may be present in the FM lesions from the initial stage of disease onset. Even if a diagnosis of idiopathic FM is confirmed, continued suspicion of the presence of hematologic malignancy is vital for improving patient outcomes.

Keywords: mediastinitis, Leukemia, Fibrosis

Introduction

Fibrosing mediastinitis (FM) is a rare, fibroproliferative disorder within the mediastinum [1–9]. Progressive fibrosis in FM encases, compresses, and obstructs vital organs such as the tracheobronchial tree, pulmonary vessels, and superior vena cava, leading to significant morbidity [2,10,11]. The main pathological findings of FM are the presence of extensive areas of paucicellular fibrous tissue with a minimal inflammatory component or the presence of fibrocollagen deposition with a variable component of inflammatory cells [3,5,6]. Autoimmune diseases (eg, IgG4-related disease, sarcoidosis), neoplastic diseases (eg, malignant lymphoma, malignant mesothelioma), and infectious diseases (eg, histoplasmosis, tuberculosis, blastomycosis, mucormycosis, cryptococcosis, aspergillosis, and nocardiosis) can cause FM [3–6,12]. Idiopathic FM is less common than FM with known causes; it involves bilateral mediastinum and is associated with poor prognoses [2,10–12]. Corticosteroid therapy is used to treat idiopathic FM, but their effects are limited [2,3,6]. Other than the presence of obvious tumor cells or pathogens in the biopsy specimen, there is no single characteristic finding that can be used to distinguish idiopathic FM from FM with known causes on histopathological findings [5]. A thorough work-up that includes a true clinical/radiological/pathological correlation and the exclusion of other causative disease is very important to make a final diagnosis of idiopathic FM or to identify a treatable underlying cause [5].

It is extremely rare for hematologic malignancies to develop as FM; our search of the relevant literature identified only 4 reports of malignant lymphoma [13–16]. In all 4 cases, the appearance of new symptoms other than FM and an increase in a tumor marker were clues to the diagnosis of a hematologic malignancy. Chemotherapy has been successful in reducing FM lesions, demonstrating the importance of finding treatable lesions even after a diagnosis of idiopathic FM is made. It is currently unknown whether cases of idiopathic FM that progress over a long period of time with only FM symptoms develop a hematologic malignancy. We have found no reports of leukemia presenting as FM, and it is unknown whether hematologic malignancy truly exists within the FM lesion from the initiation of the disease.

Here, we report the first case of B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) presenting as FM. The patient’s FM lesions preceded the appearance of blasts in his peripheral blood (PB) by >18 months, and the disease had progressed very latently until the appearance of blasts in the PB. We have shown for the first time that a patient’s B-ALL/LBL may have been present within the FM lesions from the initiation of the disease. This case report sheds new light on the pathophysiology of B-ALL/LBL, and it shows that some cases of idiopathic FM that have been present for a long time include a treatable condition.

Case Report

A previously healthy 32-year-old Japanese man noticed pain behind his eyebrows and visited on an ear/nose/throat specialist and a neurosurgeon the same day, but no diagnosis was made. He had never smoked and had no history of alcohol use. He had no history of international travel. He did not take any medications. On day 17 after the pain’s onset, edema of the face and eyelids (exacerbated in the supine position) appeared, and the patient scored 2 points on the modified Medical Research Council (mMRC) Dyspnea Scale (Figure 1). On day 22, dyspnea appeared at night and he could no longer sleep in the supine position, so he began to sleep sitting upright. Chest computed tomography (CT) on day 22 showed a diffuse soft tissue mass-like lesion in the anterior mediastinum, complicated with severe stenosis of the superior vena cava (Figure 2A, 2B). There were no enlarged lymph nodes. He was referred to our hospital for further examination on day 27.

The physical examination showed a body temperature of 37.0°C, blood pressure at 127/88 mmHg, pulse 68 beats per minute, oxygen saturation 98% while breathing ambient air, and respiratory rate at 16 breaths per minute. The patient’s Glassgow Coma Scale score was 15 (4 for eye-opening, 5 for verbal responses, and 6 for motor responses). Lung auscultation was normal. The results of cardiac and abdominal examinations were also normal. He had eyelid edema and facial swelling. There was telangiectasia on his anterior thoracic legion. Laboratory tests showed normal levels of CRP, LDH, and tumor markers, including alpha fetoprotein, beta-human chorionic gonadotropin, and soluble interleukin-2 receptor (sIL-2R). The complete hemogram was normal, without any blasts (Table 1).

To obtain a definitive pathological diagnosis, we planned a biopsy of the mediastinal lesion. We opted for the less-invasive technique. We first performed endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) on day 29. On day 30, the patient developed cervical tightness. The pathology results were known on day 34, but the specimens were too small to enable a confident diagnosis.

We scheduled a surgical biopsy and on day 45 of onset and conferred with a respiratory surgeon and anesthesiologist. However, the high risk of cerebral edema caused by general anesthesia precluded its implementation at that time. We considered the indications for radiation therapy and endovascular stenting. Radiation was not indicated because the radiation dose depends on the histological diagnosis, and endovascular stenting was not performed because of the risk of the stent straying into other blood vessels during mass reduction.

On day 35, the patient’s dyspnea had deteriorated to mMRC scale 4, his facial edema worsened, and edema of his right upper extremities was observed. We administered oral morphine sulfate hydrate to alleviate the dyspnea. A surgical biopsy was not possible at that time. On day 37, to obtain a more definitive specimen by a less-invasive method than a surgical procedure, we conducted a CT-guided biopsy from the mediastinal tumor lesion; however, the specimens were observed on day 51 to be too small to enable a confident diagnosis. On day 41, the patient was unable to lift his upper limbs due to dyspnea.

After consulting our institution’s cancer specialists, we initiated corticosteroid therapy to ameliorate the patient’s facial edema and dyspnea on day 41. To provide rapid symptomatic relief, we initiated a high intravenous dose (125 mg/day) of methylprednisolone, which retains a high non-genomic effect in combination with its genomic effect [17], for 3 consecutive days. A high dose (8 mg/day) of oral dexamethasone (which has high potency of genomic, anti-inflammatory activity and is expected to have a long duration of action) was then administered.

A few days after the initiation of corticosteroid treatment, the patient’s dyspnea and facial swelling were gradually resolved. On day 44, he had reduced facial and upper-extremity edema and was able to raise his upper extremities. A chest CT examination performed 1 week after the initiation of the corticosteroid administration showed a mild reduction in the size of the mediastinal mass-like lesion (Figure 2C, 2D).

After 6 weeks of corticosteroid therapy, the patient’s dyspnea disappeared and his facial edema was reduced. He was able to sleep in a supine position, his nocturnal dyspnea disappeared, and his general condition improved. To obtain tissue specimens of adequate quantity and quality for pathological diagnosis, we performed a surgical biopsy on day 84. The specimen was an undemarcated dense fibrotic lesion (Figure 3A, 3B). There was mild infiltration of small- to medium-sized lymphocytes. The finding of extensive and dense fibrotic lesions was considered sufficient to explain the compression of the superior vena cava, which caused symptoms such as facial edema and dyspnea. Immunohistochemically, the infiltrating lymphocytes were composed of CD3-positive T lymphocytes and CD79a- or CD20-positive B lymphocytes (Figure 3C, 3D). No obvious neo-plastic proliferations of cytokeratin AE1/AE3-positive cells, terminal deoxynucleotidyl transferase (TdT)-positive cells, or fibroblasts were detected (Figure 3E, 3F).

A diagnosis of FM is based on the clinical presentation of varying degrees of mediastinal organ compression, diffuse soft tissue shadows occupying the mediastinum, and a histopathological diagnosis characterized by the presence of extensive areas of fibrosis with minimal inflammatory component [5,6]. When infections, autoimmune diseases, and neoplastic diseases have been ruled out by a thorough work-up, FM is diagnosed as idiopathic [5,6]. The differential diagnoses are presented in Table 2. Among the inflammatory and autoimmune diseases, IgG4-related disease was ruled out in our patient’s case because there was no increase in the IgG4/IgG ratio in the tissue or in serum IgG4. Infectious diseases were ruled out because there were no pathogens, including Histoplasma capsulatum, mycobacteria, and other fungal microorganisms, in the tissue samples. Tuberculosis was also ruled out because the results of a Mycobacterium tuberculosis interferon gamma release assay was negative. Neoplastic diseases were ruled out because there was no malignant tumor growth in the surgical biopsy specimen. Malignant lymphoma was ruled out at that point because there were no obvious TdT-positive cells. At that point, the patient’s diagnosis was idiopathic FM. The pathological slides were reviewed at a specialized facility in Japan, where the same diagnosis of idiopathic FM was made. We considered the indications for endovascular intervention and surgical treatment, but since both treatments have been reported to have a high symptom recurrence rate [2], we did not implement them and continued corticosteroid therapy.

Three months after the initiation of the patient’s treatment, the dosage of dexamethasone was tapered to 2 mg/day, but symptoms including nocturnal dyspnea and neck swelling recurred. During the course of the disease, there were 4 relapses with re-enlargement of the mediastinal mass-like lesion. We attempted sampling of the right pleural effusion with the patient in both the sitting and supine positions, but there was almost no echo-free space between the visceral and parietal pleura, and it was deemed difficult to safely perform the puncture; it was thus not performed. At 13 months after the patient’s initial visit, the hilar and mediastinal lymph nodes gradually became enlarged. The level of sIL-2R showed only a slight increase during the course of disease. The patient’s clinical course is depicted in Figure 4.

Sixteen months after treatment initiation, a routine blood test detected abnormal cells incidentally on a hemogram by an automatic hematology analyzer machine. A blood smear test using the same PB sample revealed the presence of large abnormal cells with nucleoli in the patient’s PB, accounting for 13% of the PB cells (Figure 5A). A bone marrow (BM) biopsy showed hypercellularity with increased lymphocyte-like blasts which exhibited immunoreactivity for TdT (Figure 5B, 5C). The EBUSTBNA biopsy from lymph node #11L revealed the infiltration of TdT-positive blasts in the lymph node (Figure 5D, 5E). Flow cytometry (FCM) of the patient’s PB and the BM showed that the blasts in both samples were positive for CD7, CD19, and CD34 and negative for CD3, CD4, CD8, and CD20 (Figure 6A, 6B). We therefore diagnosed the patient as having B-ALL/LBL.

We initiated multi-agent chemotherapy that is used for first-onset, nonelderly patients with Philadelphia-negative ALL. The treatment regimen was the Japan Adult Leukemia Study Group (JALSG)-ALL202-O protocol, which has shown good results in Japanese patients [18]. The end of induction (EOI) BM biopsy on day 40 revealed a minimal residual disease-negative status. Six months after the EOI, a chest CT examination showed almost complete shrinkage of mediastinal mass-like lesion as well as the mediastinal and hilar lymph nodes (Figure 7). The patient is continuing chemotherapy and is currently in the maintenance phase.

We hypothesized that the lesions originally thought to be idiopathic FM were caused by B-ALL/LBL. To investigate the presence of blasts in the original lesion, we performed immunohistochemistry of CD7 and CD34, which were expressed on the blasts in both the PB and BM at the time of the patient’s B-ALL/LBL diagnosis (FCM, Figure 6A, 6B). Interestingly, we observed relatively large cell clusters expressing CD7 and CD34 in the mediastinal biopsy specimens taken at the time of the diagnosis of idiopathic FM (Figure 8). In that same area, a small cluster of TdT-positive cells was also identified. CD3 and CD20 were positive in small-sized lymphocytes with no atypia. Taken together, these results suggest that B-ALL/LBL was present in from the time of his initial presentation and manifested as idiopathic FM.

As discussed below in the Discussion section, the B-ALL/LBL in the patient’s case may have formed FM-like lesions during tumor progression by recruiting CD20-positive B lymphocytes, which are thought to contribute to the pathogenesis of FM. Therefore, it is possible that treatment targeting B-ALL/LBL resulted in almost complete shrinkage of mediastinal mass-like lesion as well as the mediastinal and hilar lymph nodes.

Discussion

To the best of our knowledge, this is the first case report identifying B-ALL/LBL that manifested as FM-like lesions. The most unique aspect of our patient’s case is the exceptional presentation of B-ALL/LBL – the extremely long period of time between the onset as FM-like lesions and the appearance of blasts in the patient’s PB. The patient’s case presented as idiopathic FM. Repeated biopsies, including a surgical biopsy obtaining a sufficient quantity and adequate quality of specimen, showed no findings of malignancy. Steroid treatment resulted in repeated relapse. Eventually, 18 months after the disease onset, blasts appeared in the PB, leading to the diagnosis of B-ALL/LBL. Even lymph node enlargement had not occurred for 13 months after the onset. The results of the reassessment by immunostaining strongly suggest that the patient’s B-ALL/LBL had developed in the form of FM from the beginning. His case may change the conventional understanding of idiopathic FM and B-ALL/LBL, and it underscores the need for ongoing and rigorous long-term monitoring for the possibility of the development of hematologic malignancies, even after a thorough clinical-radiological-pathological work-up.

Three lines of evidence indicated that our patient’s B-ALL/LBL originated in the mediastinum from the beginning and manifested as FM. First, B-ALL/LBL-targeting chemotherapy was extremely effective against FM-like lesions. Second, the immunohistochemical reassessment revealed that the CD34/CD7/TdT-positive cell clusters that characterized the B-ALL/LBL blasts in this case were present in the mediastinal biopsy tissue, which was collected 16 months before the appearance of blasts in the patient’s PB. This report provides evidence that B-ALL/LBL can present as FM long before the appearance of blasts in the PB; indeed, >18 months before then is possible.

Third, the longitudinal CT follow-up captured the gradual enlargement of hilar and mediastinal lymph nodes near the FM-like lesions before the appearance of blasts in the patient’s PB. The biopsy specimen from the enlarged hilar lymph node showed the infiltration of TdT-positive blasts.

Other than B-ALL/LBL, only 4 cases of hematologic malignancies masquerading as FM have been reported to date [13–16] (Table 3). All 4 cases were lymphomas, and no cases of leukemia presenting as FM-like lesions have been reported to our knowledge. All 4 of the above patients had no lymphadenopathy at the time of presentation, and each patient had undergone repeated biopsies and a surgical biopsy. One case was diagnosed after tumor resection [14]. Two of the patients were initially treated with corticosteroids as idiopathic FM, but the effect was limited, as in our patient’s case [15,16]. The length of time from onset to the diagnosis of hematologic malignancy in our patient was the longest of any reported case to date. The clues to the diagnosis of a hematologic malignancy were the appearance of a new mass lesion [13], painful enlargement of the cervical lymph nodes [15], and an increase in sIL-2R levels [16]. In contrast, our patient shown no new symptom onset or increase in sIL-2R throughout the course of disease. The B-ALL/LBL in his case thus followed a very latent course until blasts appeared in his PB. In the 3 reports describing the treatment response, the FM lesions had shrunk with chemotherapy for lymphoma [13,15,16]. These findings are consistent with the response of our patient’s FM-like lesions to the chemotherapy for B-ALL/LBL.

We initially considered repeated biopsies, including a surgical biopsy, and we conducted a thorough work-up of the patient’s FM lesions for identification of a treatable underlying cause. After consideration of the clinical-radiological-pathological correlation, we initially diagnosed the patient as having idiopathic FM. The effect of corticosteroids on idiopathic FM is reported to be limited [2,3,6]. However, our patient experienced a mild reduction in the size of FM lesions and relief of symptoms, and there was no alternative treatment; we thus continued corticosteroid therapy.

In this patient’s case, the diagnosis of B-ALL/LBL was delayed because (i) apparent blast infiltration was not detected in the surgical biopsy specimen; (ii) lymphadenopathy was absent at the time of the surgical biopsy; (iii) there were no new symptoms other than those caused by FM lesions; (iv) there was no increase in the sIL-2R level; and (v) no blasts appeared in the patient’s PB over the 18-month clinical course. In addition, idiopathic FM is characterized by a mixture of chronic inflammatory cells surrounding the dense fibrotic lesion, which is extremely difficult to distinguish from a blast infiltration in B-ALL/LBL with FM-like lesions, as in our patient’s case. After the identification B-ALL/LBL, we determined that the prognostic factor in this patient case was B-ALL/LBL, switched the corticosteroid treatment to chemotherapy for B-ALL/LBL, and this treatment was also effective for the FM lesions.

In the tissue of FM, there are many CD20-positive B lymphocytes infiltrating around the fibrotic lesions, and these are believed to contribute to the pathogenesis of FM [2]. In our patient, CD20-positive B lymphocytes also accumulated around a mediastinal fibrotic lesion. However, his FCM profile showed that blasts in both his PB and BM did not express CD20. A CD34/CD7/TdT-positive population was observed in the patient’s FM lesions, providing a pattern of expression common to the blasts in his PB and BM. Hematologic malignancies form a tumor microenvironment that includes the recruitment of various types of inflammatory cells during the tumor initiation and progression processes [19]. We thus speculated that our patient’s B-ALL/LBL might have recruited CD20-positive B lymphocytes during the processes of tumor development and promoted the formation of FM lesions. Regarding the impact of chronic inflammation on tumor progression, it is possible that chronic inflammation in the FM lesions might have contributed to the progression of his B-ALL/LBL via a modulation of the immune response in the tumor microenvironment, as observed in other malignancies [19]. A recent report showing that inflammation-induced overexpression of activation-induced deaminase promotes the progression of BCR-ABL1+ B-ALL supports this idea [20]. Further basic research is necessary to investigate these comprehensive mechanisms.

In ALL/LBL, lymphoid progenitor cells in the BM, PB, and extramedullary sites undergo malignant transformation [21,22]. B-ALL/LBL emerges as pure B-ALL in 80% of cases, B-LBL (with <25% BM blasts) in 10% of the cases, and mixed B-ALL/LBL in 10% of the cases [23]. Based on our patient’s clinical course (in which FM preceded the appearance of blast by 18 months) and the results of immunohistochemistry (ie, the detection of a CD34/CD7/TdT-positive population in the FM lesions), we believe that he had pure LBL at the time of onset. Mediastinal masses characteristic of T-LBL are much less common in B-LBL; the rate of mediastinal masses is 90% of T-LBL cases and 4% of B-LBL cases [23,24]. The present report is the first of B-LBL manifesting as mediastinal fibrosing masses.

Our literature search identified no reports of extramedullary fibrosis in B-ALL. However, there have been several reports of BM fibrosis in B-ALL with regard to its mode of onset and susceptibility to treatment. BM fibrosis is noted in various degrees in a certain population of individuals with B-ALL/LBL at diagnosis [25,26]. Very rarely, B-ALL presents as acute myelofibrosis (AMF) with sudden-onset pancytopenia [27,28]. In previous reports of B-ALL complicated with AMF, AMF concurrently occurred with B-ALL or preceded the diagnosis of B-ALL by approx. 3-12 months [27,29,30]. Just as B-ALL/LBL treatment was effective for the FM lesions in our patient’s case, it has been reported that B-ALL treatment led to a significant resolution of BM fibrosis in patients with AMF that preceded B-ALL [27]. We thus suspect that some of the profibrotic cytokines released from B-ALL blasts may contribute to the formation of fibrotic lesions in the mediastinum and BM.

Regarding the relationship between ALL-associated fibrosis and the therapeutic responsiveness, BM fibrosis in children with ALL was correlated with poor treatment responsiveness and shorter progression-free survival [25]. In addition, high levels of BM fibrosis prior to CD19-directed chimeric antigen receptor (CAR) T-cell therapy predicted resistance to CAR T-cell therapy and lower overall survival in pediatric patients with B-ALL/LBL [26]. In adults, the impact of BM fibrosis, much less extramedullary fibrosis, on the treatment response and prognosis of B-ALL have not been determined. It is widely accepted that fibrotic tissue as well as cancer-associated fibroblasts can be key components of the tumor microenvironment that promotes tumor progression and resistance to treatment [31,32]. Considering that our patient’s the FM was the origin of B-ALL/LBL and that advanced fibrosis in extramedullary lesions are a possible poor prognostic factor of ALL, more attention needs to be paid to the treatment response and outcome in cases of B-ALL/LBL with FM lesions.

The main limitation of this case report concerns the accuracy of the method used to detect tumor homology. Improving the detection of tumor homology between the blasts in the PB and BM, and CD34/CD7/TdT-positive cells in the FM-like lesions is crucial for diagnoses, treatments, the elucidation of pathogenic mechanisms, and prognostic evaluations. In the present patient, the CD34/CD7/TdT-positive cells in the FM-like lesions were a very small population and sparse, and it was extremely difficult to distinguish them from surrounding chronic inflammatory cells by hematoxylin-eosin staining. Laser-capture microdissection and subsequent next-generation sequencing or gene expression profiling analysis were therefore not possible. The only surface marker that was common to blasts in our patient’s PB and BM, other than CD34 and CD7, was CD19, which is expressed in all B-lineage cells. A further confirmation of tumor homology using immunostaining was thus not possible in his case.

Conclusions

We have provided the first report of B-ALL/LBL manifesting FM. This case underscores the importance of considering the possibility of latent hematologic malignancy even in the absence of new symptoms other than those caused by FM lesions for a long period of time. This is the first demonstration that leukemia cells may be present in the FM lesions from the initial stage of disease onset. We share this case report to provide new insights into understanding the pathophysiology of B-ALL/LBL. This report highlights the possible presence of a latent hematologic malignancy among patients with idiopathic FM and is of great importance in clinical practice in terms of improving diagnostic methods, treatments, and prognoses. This report emphasizes the importance of long-term suspicion of the presence of hematologic malignancies in FM lesions, even after a rigorous clinical-radiological-pathological diagnosis including a surgical biopsy, and the need for a continuous and rigorous monitoring. We propose use of the following specific methods to monitor development of hematologic malignancies in addition to obtaining sufficient quantity and quality of tissue in surgical biopsy: (i) careful observation of TdT-immunostained surgical biopsy specimens; (ii) long-term CT scan follow-up every 3-6 months to detect enlarged lymph nodes and prompt biopsy when enlarged; and (iii) rigorous PB smear testing over time, including the application of deep learning technologies. Future basic researches are needed to elucidate factors that predispose to FM formation in hematologic malignancies, including B-ALL/LBL, how hematologic malignancies form FM lesions, and how FM lesions affect hematologic malignancy progression, treatment sensitivity, and prognosis. We hope that these research advances will improve outcomes for both FM and B-ALL/LBL.

Figures

The clinical course of the early stage of the patient’s disease onset. The course of each symptom is shown in the lower column. Loxoprofen and morphine sulfate hydrate were administered to relieve cervical tightness and dyspnea, respectively. EBUS-TBNA on day 29 of onset and CT-guided biopsy on day 37 failed to reach a pathological diagnosis. A surgical biopsy scheduled on day 45 was postponed and was performed on day 84 when symptoms were relieved by steroid administration. CT – computed tomography; EBUS-TBNA – endobronchial ultrasound-guided transbronchial needle aspiration; Dex – dexamethasone; mPSL – methylprednisolone.Figure 1.. The clinical course of the early stage of the patient’s disease onset. The course of each symptom is shown in the lower column. Loxoprofen and morphine sulfate hydrate were administered to relieve cervical tightness and dyspnea, respectively. EBUS-TBNA on day 29 of onset and CT-guided biopsy on day 37 failed to reach a pathological diagnosis. A surgical biopsy scheduled on day 45 was postponed and was performed on day 84 when symptoms were relieved by steroid administration. CT – computed tomography; EBUS-TBNA – endobronchial ultrasound-guided transbronchial needle aspiration; Dex – dexamethasone; mPSL – methylprednisolone. Chest computed tomography (CT) at the patient’s first visit (A, B) showed a diffuse soft tissue mass-like lesion of the anterior mediastinum with severe stenosis of the superior vena cava (arrows) and right pulmonary artery (arrowhead). (C, D) CT at 1 week after the corticosteroid treatment. The size of the mediastinal mass-like lesion was mildly reduced, and the severe stenosis of the superior vena cava (allows) and right pulmonary artery (arrowhead) was slightly mitigated.Figure 2.. Chest computed tomography (CT) at the patient’s first visit (A, B) showed a diffuse soft tissue mass-like lesion of the anterior mediastinum with severe stenosis of the superior vena cava (arrows) and right pulmonary artery (arrowhead). (C, D) CT at 1 week after the corticosteroid treatment. The size of the mediastinal mass-like lesion was mildly reduced, and the severe stenosis of the superior vena cava (allows) and right pulmonary artery (arrowhead) was slightly mitigated. Thoracic biopsy findings of the mediastinal mass-like lesion. The specimen comprised an undemarcated dense fibrotic lesion (A, B). There was mild infiltration of small- to medium-sized lymphocytes. (C–F) Immunohistochemical findings. The infiltrating lymphocytes were composed of CD3-positive T lymphocytes and CD20-positive B lymphocytes (C, D). No apparent neoplastic proliferations of cytokeratin AE1/AE3-positive cells or terminal deoxynucleotidyl transferase (TdT)-positive cells was detected (E, F). A: 12.5×, B: 200×, C–F: 40× magnification. A, B: Hematoxylin and eosin (H&E) stain.Figure 3.. Thoracic biopsy findings of the mediastinal mass-like lesion. The specimen comprised an undemarcated dense fibrotic lesion (A, B). There was mild infiltration of small- to medium-sized lymphocytes. (C–F) Immunohistochemical findings. The infiltrating lymphocytes were composed of CD3-positive T lymphocytes and CD20-positive B lymphocytes (C, D). No apparent neoplastic proliferations of cytokeratin AE1/AE3-positive cells or terminal deoxynucleotidyl transferase (TdT)-positive cells was detected (E, F). A: 12.5×, B: 200×, C–F: 40× magnification. A, B: Hematoxylin and eosin (H&E) stain. Clinical course. Steroid administration resulted in mild reduction of mediastinal mass-like lesion. However, as the steroid dose was tapered off, there were 4 relapses with re-enlargement of the mediastinal mass-like lesion. At 13 months after the disease onset, the hilar and mediastinal lymph nodes gradually became enlarged. Eighteen months after the disease onset, a routine blood test detected abnormal cells incidentally on a hemogram. Dex – dexamethasone; M – month; mPSL – methylprednisolone; PB – peripheral blood; Rec – recurrence.Figure 4.. Clinical course. Steroid administration resulted in mild reduction of mediastinal mass-like lesion. However, as the steroid dose was tapered off, there were 4 relapses with re-enlargement of the mediastinal mass-like lesion. At 13 months after the disease onset, the hilar and mediastinal lymph nodes gradually became enlarged. Eighteen months after the disease onset, a routine blood test detected abnormal cells incidentally on a hemogram. Dex – dexamethasone; M – month; mPSL – methylprednisolone; PB – peripheral blood; Rec – recurrence. The onset of B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL). (A) Blast in the peripheral blood. (B, C) Bone marrow (BM) biopsy. BM hypercellularity with increased lymphocyte-like blasts which exhibited immunoreactivity for terminal deoxynucleotidyl transferase (TdT) was observed. (D, E) Left hilar lymph node (#11L) biopsy. Infiltration of TdT-positive blasts was observed. A: 1,000×, B–E: 400× magnification. A: May-Giemsa stain, B, D: Hematoxylin and eosin (H&E) stain.Figure 5.. The onset of B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL). (A) Blast in the peripheral blood. (B, C) Bone marrow (BM) biopsy. BM hypercellularity with increased lymphocyte-like blasts which exhibited immunoreactivity for terminal deoxynucleotidyl transferase (TdT) was observed. (D, E) Left hilar lymph node (#11L) biopsy. Infiltration of TdT-positive blasts was observed. A: 1,000×, B–E: 400× magnification. A: May-Giemsa stain, B, D: Hematoxylin and eosin (H&E) stain. Flow cytometry plots of the patient’s peripheral blood (PB) (A) and bone marrow (BM) (B). Blasts in the PB were positive for CD7, CD19, CD22, CD34, and CD38 and negative for CD2, CD3, CD4, CD5, CD8, CD10, CD11c, CD16, CD20, CD23, CD24, CD25, CD30, CD56, IgG1, IgG2a, HLA-DR, Kappa, and Lambda. Blasts in the BM were positive for CD7, CD19, and CD34 and negative for CD2, CD3, CD4, CD5, CD8, CD10, CD11c, CD13, CD14, CD15, CD16, CD20, CD22, CD24, CD33, CD41a, CD56, CD117, IgG1, IgG2a, Glycophorin A, HLA-DR, Kappa, and Lambda.Figure 6.. Flow cytometry plots of the patient’s peripheral blood (PB) (A) and bone marrow (BM) (B). Blasts in the PB were positive for CD7, CD19, CD22, CD34, and CD38 and negative for CD2, CD3, CD4, CD5, CD8, CD10, CD11c, CD16, CD20, CD23, CD24, CD25, CD30, CD56, IgG1, IgG2a, HLA-DR, Kappa, and Lambda. Blasts in the BM were positive for CD7, CD19, and CD34 and negative for CD2, CD3, CD4, CD5, CD8, CD10, CD11c, CD13, CD14, CD15, CD16, CD20, CD22, CD24, CD33, CD41a, CD56, CD117, IgG1, IgG2a, Glycophorin A, HLA-DR, Kappa, and Lambda. Chest computed tomography (CT) at the onset of B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) (A–C) and at 6 months after the end of the induction (D–F). The mediastinal mass-like lesion (arrowheads) as well as mediastinal and hilar lymph nodes (arrows) showed significant shrinkage after the B-ALL/LBL treatment. The right pleural effusion also disappeared.Figure 7.. Chest computed tomography (CT) at the onset of B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) (A–C) and at 6 months after the end of the induction (D–F). The mediastinal mass-like lesion (arrowheads) as well as mediastinal and hilar lymph nodes (arrows) showed significant shrinkage after the B-ALL/LBL treatment. The right pleural effusion also disappeared. Thoracic biopsy findings of the mediastinal mass-like lesion. Relatively large cell clusters were present nearby the fibrotic lesion (A, B). These cells were positive for CD34 (C, D), CD7 (E, F), and terminal deoxynucleotidyl transferase (TdT) (G, H, arrowheads). CD3 (I, J) and CD20 (K, L) were positive in small-sized lymphocytes with no atypia. The images in (B, D, F, H, J, L) are ×4 magnifications of the indicated regions in (A, C, E, G, I, K). A, C, E, G, I, K: 100×, B, D, F, H, J, L: 400× magnification. A, B: Hematoxylin and eosin (H&E) stain.Figure 8.. Thoracic biopsy findings of the mediastinal mass-like lesion. Relatively large cell clusters were present nearby the fibrotic lesion (A, B). These cells were positive for CD34 (C, D), CD7 (E, F), and terminal deoxynucleotidyl transferase (TdT) (G, H, arrowheads). CD3 (I, J) and CD20 (K, L) were positive in small-sized lymphocytes with no atypia. The images in (B, D, F, H, J, L) are ×4 magnifications of the indicated regions in (A, C, E, G, I, K). A, C, E, G, I, K: 100×, B, D, F, H, J, L: 400× magnification. A, B: Hematoxylin and eosin (H&E) stain.

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Figures

Figure 1.. The clinical course of the early stage of the patient’s disease onset. The course of each symptom is shown in the lower column. Loxoprofen and morphine sulfate hydrate were administered to relieve cervical tightness and dyspnea, respectively. EBUS-TBNA on day 29 of onset and CT-guided biopsy on day 37 failed to reach a pathological diagnosis. A surgical biopsy scheduled on day 45 was postponed and was performed on day 84 when symptoms were relieved by steroid administration. CT – computed tomography; EBUS-TBNA – endobronchial ultrasound-guided transbronchial needle aspiration; Dex – dexamethasone; mPSL – methylprednisolone.Figure 2.. Chest computed tomography (CT) at the patient’s first visit (A, B) showed a diffuse soft tissue mass-like lesion of the anterior mediastinum with severe stenosis of the superior vena cava (arrows) and right pulmonary artery (arrowhead). (C, D) CT at 1 week after the corticosteroid treatment. The size of the mediastinal mass-like lesion was mildly reduced, and the severe stenosis of the superior vena cava (allows) and right pulmonary artery (arrowhead) was slightly mitigated.Figure 3.. Thoracic biopsy findings of the mediastinal mass-like lesion. The specimen comprised an undemarcated dense fibrotic lesion (A, B). There was mild infiltration of small- to medium-sized lymphocytes. (C–F) Immunohistochemical findings. The infiltrating lymphocytes were composed of CD3-positive T lymphocytes and CD20-positive B lymphocytes (C, D). No apparent neoplastic proliferations of cytokeratin AE1/AE3-positive cells or terminal deoxynucleotidyl transferase (TdT)-positive cells was detected (E, F). A: 12.5×, B: 200×, C–F: 40× magnification. A, B: Hematoxylin and eosin (H&E) stain.Figure 4.. Clinical course. Steroid administration resulted in mild reduction of mediastinal mass-like lesion. However, as the steroid dose was tapered off, there were 4 relapses with re-enlargement of the mediastinal mass-like lesion. At 13 months after the disease onset, the hilar and mediastinal lymph nodes gradually became enlarged. Eighteen months after the disease onset, a routine blood test detected abnormal cells incidentally on a hemogram. Dex – dexamethasone; M – month; mPSL – methylprednisolone; PB – peripheral blood; Rec – recurrence.Figure 5.. The onset of B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL). (A) Blast in the peripheral blood. (B, C) Bone marrow (BM) biopsy. BM hypercellularity with increased lymphocyte-like blasts which exhibited immunoreactivity for terminal deoxynucleotidyl transferase (TdT) was observed. (D, E) Left hilar lymph node (#11L) biopsy. Infiltration of TdT-positive blasts was observed. A: 1,000×, B–E: 400× magnification. A: May-Giemsa stain, B, D: Hematoxylin and eosin (H&E) stain.Figure 6.. Flow cytometry plots of the patient’s peripheral blood (PB) (A) and bone marrow (BM) (B). Blasts in the PB were positive for CD7, CD19, CD22, CD34, and CD38 and negative for CD2, CD3, CD4, CD5, CD8, CD10, CD11c, CD16, CD20, CD23, CD24, CD25, CD30, CD56, IgG1, IgG2a, HLA-DR, Kappa, and Lambda. Blasts in the BM were positive for CD7, CD19, and CD34 and negative for CD2, CD3, CD4, CD5, CD8, CD10, CD11c, CD13, CD14, CD15, CD16, CD20, CD22, CD24, CD33, CD41a, CD56, CD117, IgG1, IgG2a, Glycophorin A, HLA-DR, Kappa, and Lambda.Figure 7.. Chest computed tomography (CT) at the onset of B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) (A–C) and at 6 months after the end of the induction (D–F). The mediastinal mass-like lesion (arrowheads) as well as mediastinal and hilar lymph nodes (arrows) showed significant shrinkage after the B-ALL/LBL treatment. The right pleural effusion also disappeared.Figure 8.. Thoracic biopsy findings of the mediastinal mass-like lesion. Relatively large cell clusters were present nearby the fibrotic lesion (A, B). These cells were positive for CD34 (C, D), CD7 (E, F), and terminal deoxynucleotidyl transferase (TdT) (G, H, arrowheads). CD3 (I, J) and CD20 (K, L) were positive in small-sized lymphocytes with no atypia. The images in (B, D, F, H, J, L) are ×4 magnifications of the indicated regions in (A, C, E, G, I, K). A, C, E, G, I, K: 100×, B, D, F, H, J, L: 400× magnification. A, B: Hematoxylin and eosin (H&E) stain.

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923