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A rare case of pulmonary lymphomatoid granulomatosis that clinically mimics sarcoidosis


1 University of Health Sciences, Ataturk Chest Diseases and Chest Surgery Education and Research Hospital, Department of Pathology, Ankara, Turkey
2 Katip Celebi University, Faculty of Medicine, Department of Pathology, Izmir, Turkey
3 University of Health Sciences, Ataturk Chest Diseases and Chest Surgery Education and Research Hospital, Department of Chest Surgery, Ankara, Turkey

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Date of Submission04-May-2021
Date of Decision03-Jun-2021
Date of Acceptance16-Jul-2021
Date of Web Publication24-May-2022
 


How to cite this URL:
Demirag F, Cakir E, Findik G. A rare case of pulmonary lymphomatoid granulomatosis that clinically mimics sarcoidosis. Indian J Pathol Microbiol [Epub ahead of print] [cited 2022 Sep 28]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=345871




Dear Editor,

Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive, EBV-associated B-cell lymphoproliferative disorder and the diagnosis is challenging because it is exceedingly rare and the histological features may be very subtle.[1] We would like to present a case of LYG affecting lung and skin which clinically mimics sarcoidosis. A 45-year-old woman was admitted to the hospital with dyspnea lasting for 5 years. She had also a history of repetitive nodular skin lesions lasting for 4 years. An incisional biopsy was performed by an outside dermatologist and reported as granulomatous inflammation pathologically. Computed tomography revealed bilateral paranchymal reticulonodular infiltrates in the inferior and middle lung lobes associated with mediastinal enlarged lymph nodes [Figure 1]a. The patient was consulted to our hospital with a preliminary diagnosis of sarcoidosis.
Figure 1: (a) Computed tomography showing bilateral paranchymal reticulonodular infiltrates, and mediastinal enlarged lymph nodes. (b)Skin biopsy exhibited infiltration of lymphocytes and histiocytes in the dermis and subcutis associated with granuloma formation (H&E, X200). (c) Lung biopsy showing infiltration of small lymphocytes, histiocytes and occasionally plasma cells with an angiocentric pattern (H&E, X200). (d) EBV (EBER) positivity by in situ hybridization

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Physical examination revealed an external shift in the left eye and cranial tomography was normal. Gallium-67 scintigraphy showed lambda sign characterized by abnormally high uptake in bilateral hilar and mediastinal lymph nodes. A raised serum ACE was observed. There was no remarkable pathology in transbronchial biopsy and salivary gland biopsy. Skin biopsy diagnosed at the external center was re-evaluated and an angiocentric infiltration of lymphocytes and histiocytes in the dermis and subcutis associated with granuloma formation was observed [Figure 1]b. Scattered atypical medium- to large-sized lymphocytes mimicking Reed-Sternberg cells drew attention. Immunohistochemical analysis of skin biopsy showed that the infiltration was diffusely and strongly positive for CD3 and CD68, focally positive for CD20 negative for CD30. The diagnosis was suspicious for lymphoma so a lung biopsy was performed to clarify the lung lesions.

Microscopic examination of the lung biopsy revealed a polymorphous infiltrate with an admixture of small lymphocytes, histiocytes, and occasionally plasma cells. The infiltrates tended to have a patchy distribution concentrating around interlobular septa and bronchovascular structures with an angiocentric and angiodestructive pattern and mimicking a vasculitis [Figure 1]c. Atypical medium to large lymphoid cells were infrequently seen. Immunohistochemically the majority of small lymphocytes within the vessel walls were positive with CD3. Large atypical cells were positive with CD20 and positive with EBV (EBER) by in situ hybridization [Figure 1]d. The diagnosis was LYG. The patient died 1 month after receiving the diagnosis.

Liebow first described LYG as a disease characterized by polymorphic lymphomatoid infiltrate, angiitis, and granulomatosis but it was included as a distinct disease entity in the 2001 WHO classification as a lymphoproliferative disorder of indeterminate malignant potential.[1] It is an EBV-driven lymphoproliferative disease involving extranodal sites. According to the latest WHO classification, LYG is classified under the heading of 'Mature B Cell Neoplasms' and graded according to the proportion of EBV positive B cells. Pulmonary involvement occurs in more than 90% of patients and is usually present at initial diagnosis. Other common sites of involvement are brain, kidneys, liver, and skin.[2]

Histopathologic diagnosis of LYG in grades 1 and 2 is difficult because the atypical cells are inconspicuous within the background of inflammatory cells.

Staining with CD20 and EBV to highlight these atypical cells is necessary to evaluate their density and angiocentric distribution. The characteristic histological findings of LYG in the skin are subcutaneous panniculitis associated with frequent non-necrotizing granulomas.[1]

The differential diagnosis of LYG includes inflammatory disorders such as Wegener granulomatosis and lymphomas. There are only a few case reports of LYG mimicking sarcoidosis in the literature.[3],[4] The clinical presentations of sarcoidosis and LYG are similar to nonspecific pulmonary complaints and constitutional symptoms. They also have similar radiographic findings such as bilateral, ill-defined reticular/nodular densities. In the present case, presumptive diagnosis of sarcoidosis was suggested by the radiologic findings, raised serum ACE, presence of granulomas in the skin biopsy, and a lambda sign by Gallium-67 scintigraphy. But lung biopsy with prominent angioinvasion by small T cells associated with scattered large EBV positive atypical B-cells provided the accurate diagnosis.

The clinical behavior of LYG ranges from an indolent process to an aggressive large B cell lymphoma. Historically steroids and chemotherapy were the most common treatment modalities. Recently, the use of chemoimmunotherapy and/or interferon has resulted in 5-year overall survival rate of 70%.[5] LYG is an extremely rare EBV-associated B-cell lymphoproliferative disorder and must be kept in mind in cases of suspected sarcoidosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Song JY, Pittaluga S, Dunleavy K, Grant N, White N, Jiang L, et al. Lymphomatoid granulomatosis, a single institute experience: Pathologic findings and clinical correlations. Am J Surg Pathol 2015;39:141-56.  Back to cited text no. 1
    
2.
Swerdlow SH, Campo E, Harris LN, Jaffe ES, Pileri SA, Stein S, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer; 2017. p. 312-4.  Back to cited text no. 2
    
3.
Fitch PS, Smith ME, Davies MG, Prentice AG. A case of lymphomatoid granulomatosis mimicking sarcoidosis. Respir Med 1998;92:966-8.  Back to cited text no. 3
    
4.
Koh PS, Foyle AH, Cartier Y, Langley GR, Morrison NJ, Rocker G, et al. Atypical presentation of lymphomatoid granulomatosis in a patient with long standing sarcoidosis. Can Respir 2004;11:51-4.  Back to cited text no. 4
    
5.
Roschewski M, Wilson WH. Lymphomatoid granulomatosis. Cancer J 2012;18:469-74.  Back to cited text no. 5
    

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Correspondence Address:
Ebru Cakir,
Katip Celebi University, Medical Faculty, Department of Pathology, Izmir
Turkey
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_438_21



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