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Autopsy and Case Reports

versión On-line ISSN 2236-1960

Autops. Case Rep. vol.10 no.2 São Paulo  2020  Epub 21-Oct-2020 

Letter to the Editor

Sarcoid-like reaction: Hodgkin’s lymphoma is a hypothesis

Cristiano Claudino Oliveiraa  b

aSão Paulo State University (UNESP), Botucatu School of Medicine, Department of Pathology. Botucatu, SP, Brazil.

bHospital São Luiz/D’Or. São Paulo, SP, Brazil.

Keywords  Hodgkin lymphoma; bone marrow; immunohistochemistry

Dear editor,

I, herein, present an intriguing concern of the Pathologist facing granulomas in surgical pathology routine. Inflammatory findings in surgical pathology may challenge pathologists in the setting of the diagnosis of Hodgkin’s lymphoma (HL). Consequently, Pathologists’ reports may also challenge Hematologists during the clinical practice due to the overlap of neoplastic and non-neoplastic diseases. In this context, we present a collection of findings from two patients diagnosed with HL, which had a sarcoid-like pattern in their morphological presentation.1,2

The first case is a 53-year-old woman with mental confusion for four days, without lymph adenomegaly, hepatosplenomegaly, or palpable masses. She had pancytopenia and normal values of lactate dehydrogenase and high levels of serum ferritin (9,621 mg/dL, reference range [RR] 20-110 mg/dL). Her bone marrow biopsy has shown hemophagocytosis, non-caseating epithelioid granulomas, and some binucleated large cells with evident nucleoli that reacted positive for CD30 and CD15, confirming the diagnosis of HL (Figure 11D and Figure 2).

Figure 1 Photomicrograph of the bone marrow. A – Bone marrow aspirate demonstrated hemophagocytosis, which is compatible with the clinical aspects of the patient, and it is possible in the neoplastic context, for example, HL (Giemsa, 1000x); B – Cytological aspect Reed-Sternberg cell in the bone marrow aspirate (Giemsa, 1000x); C – there is a granulomatous aspect. D there are some atypical cells in the periphery of this granulomatous pattern. These atypical cells have morphological aspects of Reed-Sternberg cells and Hodgkin cells [C (H&E, 400x) and D (H&E, 400x)]. 

Figure 2 Photomicrograph of the bone marrow. Positivity to CD30 confirmed the diagnosis of HL (400x). 

The second patient is a 44-year-old man with cervical lymph adenomegaly, without other symptoms. Histopathological analysis of the lymph node showed several non-caseating granulomas. In the periphery of the granulomas, there were some binucleated large cells, in a typical Reed-Sternberg cell aspect. The reactions for CD30, CD15, and LMP-1 were positive in these cells, confirming the HL diagnosis (Figure 33D and 4A). The Ziehl-Neelsen and Grocott-Gomori stains were negative in both cases.

Figure 3 Photomicrograph of the lymph node. A – Lymph node altered architecture. There are many granulomas in a sarcoid-like aspect. However, in the granulomas’ periphery, there are some atypical cells that are presented in the image (H&E, 200x); B – Presence of Hodgkin cells intermingled with the lymphocytes (H&E, 400x); C – positive reaction to CD15 (400X); D – positive reaction to LMP-1/EBV (arrowhead) (400X). 

Figure 4 Photomicrograph of the lymph node. Positive reaction to CD 30 (400X). 

The morphology characterized by granulomas and inflammatory infiltration always leads the Pathologists to differentials as sarcoidosis, mycobacteriosis, and mycosis. The cases, presented in this letter, draw the attention to remember the possibility of lymphoid neoplasm, as HL. Epithelioid granulomas in the bone marrow or lymph nodes of patients presenting nonspecific clinical features is a diagnostic challenge to the pathologist because of the possibility of various diagnoses, namely (i) autoimmune disease, (ii) inflammatory entity, and neoplasia.2,3 Specific study must be performed in this morphological context, and the diagnosis of HL should ever be considered. In lymph nodes, HL may mimic sarcoidosis, like in the second case. Pathologists must observe the periphery of granulomas because the atypical cells locate in this area. Careful morphological analysis with an immunohistochemistry (IHC) study is crucial.

In the absence of typical HL morphology and IHC profile, the diagnosis will be made later.

Non-caseating granulomas strongly raise the hypothesis of sarcoidosis, a systemic disease that affects different organs and has been reported before or concomitant with carcinomas (4.4%), non-Hodgkin lymphomas (7.3%) and HL (13,8%). The presence of these granulomas in the context of an HL is called a sarcoid-like reaction. This pattern is a result from degenerative and necrotic changes within the tumoral lesions, which leads to an increased level of inflammatory factors that cause the activation of macrophages or from an anti-neoplastic immune phenomenon, which is associated to a better prognosis.3-5 HL is a neoplasm with a marked reactive component and the presence of granulomas may be challenging for pathologists, mainly when they are plenty.

The presence of granulomas is described as a pattern of reaction that may occur in mixed cellularity classical HL (MC-cHL), a variant of this type of tumor, similar to the interfollicular subtype, and the grade 2 nodular sclerosis cHL (NS-cHL) group. The later shows a morphology characterized by intermingled fibrosis or fibro-histiocytic and more aggressive behavior.1

Sarcoidosis, as lymphomas, activated the histiocytic system, and therefore involve the same organs. Due to their similar clinical manifestations, the diagnosis cannot rely only on the clinical-radiological background. Clinicians should think in malignancy if there are concomitant respiratory symptoms and bilateral hilar lymphadenopathy with tomographic imaging indicating the involvement of right paratracheal and bilateral hilar lymph nodes. However, sarcoidosis may present the same clinical aspects. So, the histology is of paramount importance.2,5,6

In our cases, both patients were submitted to classical chemotherapy, with a good response. These two cases teach us the approach for granulomatous lymphadenopathy: firstly, an infection investigation with special stains, close morphology analysis, and, if there is a possibility of neoplasm, perform IHC, the gold standard for diagnosis.

How to cite: Oliveira CC. Sarcoid-like reaction: hodgkin’s lymphoma is a hypothesis. Autops Case Rep [Internet]. 2020;10(2):e2020172.

Financial support: None


1 Agostinelli C, Pileri S. Pathobiology of hodgkin lymphoma. Mediterr J Hematol Infect Dis. 2014;6(1):e2014040. PMid:24959337. [ Links ]

2 Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H. World Health Organization Classification of Tumors: pathology and genetics tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2017. [ Links ]

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4 Epelbaum R, Ben-Arie Y, Bar-Shalom R, et al. Benign Proliferative Lesions Mimicking Recurrence of Hodgkin’s Disease. Med Pediatr Oncol. 1997;28(3):187-90.<187::AID-MPO6>3.0.CO;2-F. PMid:9024514. [ Links ]

5 Fallah M, Liu X, Ji J, Försti A, Sundquist K, Hemminki K. Autoimmune diseases associated with non-Hodgkin lymphoma: a nation wide cohort study. Ann Oncol. 2014;25(10):2025-30. PMid:25081899. [ Links ]

6 Fallanca F, Picchio M, Crivellaro C, et al. Unusual presentation of sarcoid-like reaction on bone marrow level associated with mediastinal lymphadenopathy on F-FDG-PET/CT resembling an early recurrence of Hodking’s Lymphoma. Rev Esp Med Nucl Imagen Mol. 2012;31(4):207-9. PMid:22980128. [ Links ]

Received: March 12, 2020; Accepted: April 08, 2020

Conflict of interest: None

Correspondence Cristiano Claudino Oliveira Department of Pathology - Hospital São Luiz/D’Or Rua das Perobas, 266 – Jardim Oriental – São Paulo/SP – Brazil CEP: 04321-120 Phone: +55 (11) 5018-4800

Creative Commons License This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium provided the article is properly cited.