Yonago Acta medica 2011;54:83–86

Mediastinal Malignant Lymphoma Difficult to Diagnose:
A Patient Report
Ken Miwa, Hiroshige Nakamura, Yasuaki Kubouchi, Yuki Matsuoka, Yohei Yurugi,
Yuzo Takagi, Tomohiro Haruki, Shinji Fujioka and Yuji Taniguchi
Division of General Thoracic Surgery, Tottori University Hospital, Yonago 683-8504, Japan

We report a 58-year-old man who suffered from shortness of breath on exertion withwheezing. A chest enhanced computed tomography (CT) scan showed an irregular tumor
in the middle mediastinum involving the right main pulmonary artery, vena cava superior
and right main bronchus. Transbronchial lung biopsy and endobronchial ultrasoundguided transbronchial needle aspiration yielded no evidence for a pathological diagnosis ofmalignancy. We employed mediastinoscopy, which led to a diagnosis of lymphoid reactivechange. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan revealed
a high FDG uptake in the tumor lesion. Because the CT scan and FDG-PET findings led
to a marked suspicion of malignancy, we decided to attempt biopsy by a video-assisted thoracoscopic surgery (VATS) approach. Flow cytometry showed a monoclonal pattern, andthe final diagnosis was mediastinal follicular lymphoma both pathologically and immunohistologically. The patient achieved a complete remission by following chemotherapy. Lowgrade malignancy type of lymphoma such as follicular lymphoma that generally contains
small-cell components often presents a diagnostic challenge and the VATS approach waseffective for the diagnosis of such type of mediastinal lymphoma.
Key words: follicular lymphoma; malignant lymphoma; mediastinal tumor
referred to our department. The serum C-reactive
protein was slightly high, at 2.07 mg/dL, the tumor marker Sialyl Lex-i antigen was high, at 52 U/mL, and other tumor markers were within normallimits. Chest X-ray showed an ill-defined mass in
the right hilum, accompanied by secondary pneumonia in the right lung field. The chest enhanced
computed tomography (CT) scan (Fig. 1) revealed atumor about 9 by 5 cm extending from the middle
mediastinum to the right hilum, involving the rightmain pulmonary artery, superior vena cava andright main bronchus, becoming a conglomeratemass with lymph nodes. Bronchoscopic biopsy of
the tumor extending from the mediastinum to theLow-grade malignancy type of lymphoma often
presents a diagnostic challenge (Jaffe, 2009). We
report a case of mediastinal follicular lymphoma
which could not be diagnosed employing bronchoscopic or mediastinoscopic biopsy, but was finallydiagnosed using thoracoscopic biopsy, with a review of the literature.

Patient Report
A 58-year-old man experienced exertional dyspnea
and wheezing, and visited a local hospital. Chest
X-ray showed right hilar enlargement, and he was

Abbreviations: CD, cluster of differentiation; CT, computed tomography; EBUS-TBNA, endobronchial ultrasound-guided transbronchial needle aspiration; FDG-PET, 18F-fluorodeoxyglucose-positron emission tomography; VATS, videoassisted thoracoscopic surgery

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K. Miwa et al.

ings. Re-bronchoscopy identified edema and stenosis at the orifice of the right B6 bronchus. Biopsiesof the spurs at the orifices of B6 and B7 bronchi
showed the infiltration of small lymphocytes,
which was considered difficult to diagnose. Since
the chest CT findings raised a strong suspicion ofa malignant tumor, mediastinoscopic biopsy wasperformed on a grayish-white, enlarged pretracheal
lymph node. Frozen-section examination revealed
no epithelial components, thus excluding malignant
tumors such as lung cancer, and leading to a suspicion of malignant lymphoma. However, the degreeof lymphocytic atypia was slight, and the resultsof flow cytometry indicated a benign lesion, which
led to the only diagnosis of a reactive lymph node.
18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed a high FDG uptake inthe tumor extending from the middle mediastinum
to the right hilum, with maximum standardized
uptake values of 11.55 in the early phase and 13.23
in the delayed phase. Since these findings raised astrong suspicion of a malignant tumor, we decided
to perform a thoracoscopic biopsy. Thoracoscopy
revealed an ill-defined, whitish tumor diffusely
invading from the pulmonary hilum to the middle
mediastinum (Fig. 2). From the tumor, we took abiopsy sample about 4 by 2 cm. HistopathologicalFig. 1. Chest CT scan shows an irregular tumor about 9 ×
6 cm in size in the middle mediastinum expanding to theright hilum involving the right main pulmonary artery,vena cava superior and right main bronchus. CT, computed tomography.

right hilum did not show a clearly abnormal masslesion in the lumen, but the angle of the bifurcation
between the middle lobar branch and inferior main
bronchus was dull. Biopsies from the orifices of theright B5, B6 and B8 bronchi revealed no malignantlesions. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsiesof the subcarinal lymph node and right main bronchus lymph node also showed no malignant find-Upper lobe

HeadPericardium
Tumor

Middle lobe
Fig. 2. Intraoperative findings. Biopsy of the middle mediastinal tumor.

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Mediastinal malignant lymphoma

Fig. 3. Histopathological findings.
a: Pathological findings. The biopsy specimen shows monotonous proliferation with small-sized atypical lymphocytes(hematoxylin and eosin staining). Bar = 50 µm.
b: Immunohistchemical findings. Malignant cells are positive for CD 10. Bar = 50 µm.

examination revealed many small atypical lymphocytes (Fig. 3a), which showed monoclonality on
flow cytometry. Immunohistochemically, the lymphocytes were positive for cluster of differentiation(CD)10 (Fig. 3b), CD20, CD79 and B-cell lym-

phoma 2, weakly positive for CD5, only partially
positive for CD23 and negative for CD3 and cyclin
D1, leading to a final diagnosis of B-cell follicularlymphoma. The patient received six courses of chemotherapy (rituximab, cyclophosphamide, doxoru85

K. Miwa et al.

bicin, vincristine and prednisolone). At present, 13months after complete remission, he remains freeof recurrence.

lignant lymphoma may present a diagnostic challenge, we finally performed thoracoscopic surgery.
If the tumor is located in the middle mediastinum,
thoracotomy or thoracoscopic biopsy is useful for
diagnostic purposes (Toba et al., 2008). They suggested that performing thoracoscopic biopsy initially may be advisable. In the present patient, a definitive diagnosis was made after re-evaluating thehistological diagnosis based on the results of flow
cytometry. This case made us re-recognize the difficulty of diagnosing low-grade malignant type oflymphoma and the importance of consultation withpathologists.

Discussion
Although the World Health Organization classification of malignant lymphomas was revised in
2008, it is still overly complicated, and the detailsof treatment vary greatly from one subtype of lymphoma to another. Farmer and coworkers reported
that malignant lymphoma must be diagnosed moreaccurately and precisely than any other diseases,
but that the diagnosis of malignant lymphoma insmall tissue samples was difficult (Farmer et al.,2007). As they stated, this is because the histological structure is most important for the distinction oflymphomas, such as follicular lymphoma and diffuse large B-cell lymphoma, derived from germinal center cells, and because follicular lymphoma
generally contains small-cell components, but does
not have characteristic immunophenotypes (Farmeret al., 2007). EBUS-TBNA biopsy worked as thedecisive method in diagnosing mediastinal follicular lymphoma in a patient (Inoue et al., 2010); however, it is clear that some cases present diagnostic
challenges (Jaffe, 2009).
In the present patient, imaging suggested thepossibility of mediastinal metastatic lung cancer
and a malignant mediastinal tumor. We performed
both multiple bronchoscopic and mediastinoscopic
biopsies, but were unable to make a diagnosis. If
biopsies provide adequate tissue, follow-up is anoption. However, considering that patients with ma-References
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Farmer PL, Bailey DJ, Burns BF, Day A, LeBrun DP.
The reliability of lymphoma diagnosis in small tissue
samples is heavily influenced by lymphoma subtype.
Am J Clin Pathol 2007;128:474–480.
Inoue M, Nakajima T, Tsujimura H, Itami M, Sakairi
Y, Kimura H, et al. Mediastinal follicular lymphoma
diagnosed with multidirectional analysis using tissue samples obtained by EBUS-TBNA. Inter Med
2010;49:2147–2179.
Jaffe ES. The 2008 WHO classification of lymphomas:
implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program
2009:523–531.
Toba H, Kondo K, Yoshida M, Kenzaki K, Miyoshi T,Sakiyama S, et al. Clinical experience with 16 cases of
mediastinal lymphoma. Kyobu Geka 2008;61:97–101 (inJapanese with English abstract).
Received August 25, 2011; accepted September 12, 2011
Corresponding author: Ken Miwa, MD

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