Ann Thorac Surg 2007;83:2197-2199
© 2007 The Society of Thoracic Surgeons
Case Reports
Nodular Lymphoid Hyperplasia of the Lung: A Very Rare Disease Entity
Hiroyuki Sakurai, MDa,*,
Masao Hada, MDa,
Toshio Oyama, MDb
a Department of Surgery, Yamanashi Prefectural Central Hospital, Yamanashi, Japan
b Department of Pathology, Yamanashi Prefectural Central Hospital, Yamanashi, Japan
Accepted for publication December 28, 2006.
* Address correspondence to Dr Sakurai, Department of Surgery, Yamanashi Prefectural Central Hospital, 1-1 Fujimi 1-chome, Kofu, Yamanashi, 400-0027, Japan (Email: sakuraihm{at}ybb.ne.jp).
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Abstract
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Nodular lymphoid hyperplasia of the lung is an uncommon disease that is considered to be a benign lesion of a polyclonal lymphoid proliferation. Because of its rarity, little is known about the clinicopathologic characteristics of nodular lymphoid hyperplasia. Some researchers have questioned whether nodular lymphoid hyperplasias are truly reactive or are marginal zone B-cell lymphomas (low-grade lymphomas of mucosa-associated lymphoid tissue) mimicking reactive lymphoid processes. We present the case of a 67-year-old woman with nodular lymphoid hyperplasia of the lung and discuss the current knowledge concerning nodular lymphoid hyperplasias.
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Introduction
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Nodular lymphoid hyperplasia (NLH) is a rare lymphoproliferative disorder that is considered to be a localized reactive lymphoid proliferation [1]. Although NLH was initially described as pseudolymphoma [2], which is an equivocal term, the concept of NLH has been confirmed by the most recent World Health Organization (WHO) classification [3]. Because there have very few reports on NLH, little is known about its clinicopathologic features. We present a case of surgically resected NLH and review the literature on NLH.
A 67-year-old woman presented with an abnormal shadow on a routine chest roentgenogram in August 2003. She was diagnosed with multiple sclerosis at the age of 35 years. Chest computed tomography (CT) revealed a nodular lesion partially adjacent to the visceral pleura in the superior segment of the right lower lobe of the lung. Her family history was unremarkable. Physical examination disclosed no abnormalities except for a neuropathic bladder attendant on the multiple sclerosis. Bronchoscopic biopsy gave negative results.
Owing to the need for diagnostic confirmation of the pulmonary nodule, an open lung biopsy was performed from the right lung through a thoracotomy, and the lesion was resected by superior segmentectomy of the lower lobe in November 2003. Pathologic analysis of intraoperative frozen sections of the lesion showed suspected lymphoid proliferation, such as malignant lymphoma.
In the resected specimen, the tumor’s largest dimension was 3.0 cm, it was elastic and soft, and the cut surface showed relatively well-circumscribed and smooth visceral pleura with no indentation. Pathologically, the tumor showed dense infiltration of mature lymphocytes and plasma cells, which consisted of reactive germinal centers (Fig 1). Immunohistochemically, plasma cells that were reactive for both 
and 
light chain immunoglobulins, supporting a polyclonal population, and lymphocyte subset markers such as CD20 and CD3 showed an admixture of B cells and T cells. The firm diagnosis was nodular lymphoid hyperplasia (NLH).
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Fig 1. Photomicrographs show nodular lymphoid hyperplasia. The lesion shows abundant reactive germinal centers with infiltration of mature lymphocytes and plasma cells. (A) Original magnification x100 and (B) original magnification x400; both are stained with hematoxylin and eosin.
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The patient’s postoperative course was uneventful, and she is alive, with no evidence of pulmonary relapse, 36 months after the operation.
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Comment
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In 1983, Kradin and Mark [4] first suggested the term nodular lymphoid hyperplasia, which is thought to be a benign lesion consisting of a reactive lymphoid proliferation. The cause of NLH is unclear. NLH has recently been recognized in the histologic typing of lung and pleural tumors by the WHO [3]. NLH can develop at a wide variety of sites other than the lung [5]. Although NLH has been considered to be a synonym of "pseudolymphoma," as initially proposed by Saltzstein in 1963 [2], pseudolymphoma is now considered to be an ambiguous term that includes mucosa-associated lymphoid tissue (MALT) lymphoma, nodular lymphoid hyperplasia, and other low-grade lymphoproliferative diseases [6]. Actually, Addis and colleagues [7] advocated that all but cases of pseudolymphoma could, when carefully reappraised, be classified as low-grade lymphoma such as MALT lymphoma [7].
It is, therefore, important to differentiate NLHs from MALT lymphomas, although this is sometimes difficult. Histologically, NLH consists of abundant lymphoid tissue showing reactive germinal centers, interfollicular mature plasma cells and reactive small lymphocytes, and diverse amounts of interfollicular fibrosis [1]. Immunohistochemically, NLH shows a polyclonal population of lymphocytes and plasma cells [1, 8]. More specifically, both and light chain immunoglobulins are detectable in the plasma cells, and lymphocyte subset markers likewise show an admixture of B cells and T cells. Conversely, MALT lymphoma is a diffuse infiltrating lesion that consists of polymorphic lymphocytes and plasma cells. In addition, most cases show a monoclonal population [1].
The pathology specimen in the present case was also reviewed, and the NLH diagnosis supported, by William Travis, MD, from the Department of Pathology, Memorial Sloan Kettering Cancer Center. In this case, the lesion consisted of nodular mass with lymphoid cells separated by fibrous bands, and there were numerous well-defined germinal centers with clearly recognizable mantle zones. Sheets of plasma cells were also present in between the germinal centers. The plasma cells were polyclonal by and immunohistochemistry and in situ hybridization. The germinal centers were highlighted by the CD20, and the T cells and mantle zones were highlighted by the CD5, CD3, and Bcl-2. These results fitted well for NLH.
According to a report by Abbondanzo and associates [1], most patients with NLH were asymptomatic and middle-aged or older, with no predisposition to either sex. The most common radiographic findings of NLH are solitary pulmonary nodules, mostly measuring 2 to 4 cm in diameter, and occasionally multiple lesions. Approximately 90% of NLH lesions were located at the subpleura. Chest CT findings of NLH show a solid lesion with or without ground-glass opacity [5, 6], and it usually has no pleural indentation despite its subpleural location. Positron emission tomography may be helpful in the diagnosis of NLH, differing from malignancy, although it was not performed in the present case.
Kajiwara and colleagues [6] suggested the possibility of natural regression based on a case in which some NLH lesions decreased in size during the follow-up period [6]. Conversely, owing to the presence of multiple lesions in a case of NLH, it is possible that there may be a spectrum from NLH to lymphoid interstitial pneumonia [1]. NLH may also hide localized clones of lymphoma, because some cases of MALT lymphoma show many reactive germinal centers [1]. Ultimately, it is still unclear whether NLHs are genuinely reactive or MALT lymphomas imitating reactive lymphoid lesions. An association with autoimmune disease or a familial tendency has been suggested in some cases of NLH [5, 8], and multiple sclerosis was noticed in the present case.
The diagnosis of NLH, when attempted by transbronchial biopsy or transthoracic needle biopsy, can often be difficult because findings of reactive lymphoid proliferation can also be detected in primary lung cancer, lymphoma, or inflammation. Surgical excision may be the diagnostic procedure of choice for NLH. The prognosis of NLH after surgical resection seems to be excellent [1]. Long-term follow-up is required, however, because this disease is still not sufficiently understood.
In conclusion, NLH is a rare disease of unidentified etiology. Little is known about its incidence or natural history because of its rarity and controversial entity. The accumulation of additional cases and modern immunohistochemical and molecular studies will be required to elucidate the clinicopathological conditions in NLH.
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Acknowledgments
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We are grateful to William D. Travis, MD, Department of Pathology, Memorial Sloan Kettering Cancer Center, for a pathologic review of the manuscript and his suggestions.
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References
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- Abbondanzo SL, Rush W, Bijwaard KE, Koss MN. Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases Am J Surg Pathol 2000;24:587-597.[Medline]
- Saltzstein SL. Pulmonary malignant lymphomas and pseudolymphomas: classification, therapy, and prognosis Cancer 1963;16:928-955.[Medline]
- Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E. Histological typing of lung and pleural tumors, World Health Organization international histological classification of tumors. 3rd ed.. Berlin, Germany: Springer, Inc; 1999.
- Kradin RL, Mark EJ. Benign lymphoid disorders of the lung, with a theory regarding their development Hum Pathol 1983;14:857-867.[Medline]
- Kawahara K, Shiraishi T, Okabayashi K, et al. Nodular lymphoid hyperplasia in the lung Thorac Cardiovasc Surg 1996;44:210-212.[Medline]
- Kajiwara S, Sakai S, Soeda H, et al. Multifocal nodular lymphoid hyperplasia of the lung J Thorac Imaging 2005;20:239-241.[Medline]
- Addis BJ, Hyjek E, Isaacson PG. Primary pulmonary lymphoma: a re-appraisal of its histogenesis and its relationship to pseudolymphoma and lymphoid interstitial pneumonia Histopathology 1988;13:1-17.[Medline]
- Koss MN. Pulmonary lymphoid disorders Semin Diagn Pathol 1995;12:158-171.[Medline]
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Abstract
Introduction
