SciELO - Scientific Electronic Library Online

 
vol.136 issue4Complex karyotype including ring chromosome 11 in a patient with acute myeloid leukemia: case reportProlonged survival after surgical resection of cerebral metastasis from melanoma with multisystemic metastasis already present: a case report and literature review author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

Related links

Share


Sao Paulo Medical Journal

Print version ISSN 1516-3180On-line version ISSN 1806-9460

Sao Paulo Med. J. vol.136 no.4 São Paulo July/Aug. 2018  Epub July 31, 2017

http://dx.doi.org/10.1590/1516-3180.2016.0333170217 

CASE REPORT

Report of a rare case of histiocytic necrotizing lymphadenitis with bilateral pleural effusion diagnosed via cervical lymph node biopsy

Xuchun LiuI 

Shubin HuangII 

Guohua JiangIII 

IMD. Specialist, Department of Respiratory Medicine, Chizhou People’s Hospital, Chizhou, Anhui, China.

IIMD. Specialist, Department of Pathology, Chizhou People’s Hospital, Chizhou, Anhui, China.

IIIMD, PhD. Professor, Department of Respiratory Medicine, Chizhou People’s Hospital, Chizhou, Anhui, China.

ABSTRACT

CONTEXT:

Histiocytic necrotizing lymphadenitis (HNL) is a rare disorder that is often benign and self-limiting. There have been reports of co-occurrence of HNL with other diseases, including systemic lupus erythematosus, hemophagocytic syndrome and antiphospholipid syndrome.

CASE REPORT:

Here, we report a case in which a patient experienced unexplained fever, swelling of the cervical lymph node and bilateral pleural effusion and was ultimately diagnosed with HNL based on results from a lymph node biopsy. After treatment with glucocorticoid, the patient regained normal body temperature, the swelling of the lymph nodes disappeared and the pleural effusion was reabsorbed.

CONCLUSIONS:

The pathogenesis of HNL remains unclear, and pleural effusion is rarely reported in HNL patients. We presented this case to improve diagnostic awareness of this condition among clinicians and help reduce the likelihood of misdiagnosis.

KEY WORDS: Histiocytic necrotizing lymphadenitis; Pleural effusion; Tuberculosis; Lymph nodes; Biopsy

INTRODUCTION

Histiocytic necrotizing lymphadenitis (HNL) is a rare disorder, and its pathogenesis remains unclear. Some scholars believe that HNL is not an independent disease and that it may be a manifestation of an underlying autoimmune disorder; as such, the diagnosis and treatment for HNL should be targeted to the underlying disease instead. There have been reports of co-occurrence of HNL with other diseases, including systemic lupus erythematosus (SLE), hemophagocytic syndrome and antiphospholipid syndrome.1,2

However, pleural effusion has rarely been reported in HNL patients. Here, we report a case in which the patient experienced unexplained fever, swelling of the cervical lymph node and bilateral pleural effusion and was ultimately diagnosed with HNL based on the results from a lymph node biopsy.

CASE REPORT

A 26-year-old woman was hospitalized due to anorexia and fatigue that had lasted one month. Then days before admission, the patient began to experience intermittent chills and a fever between 38.5 and 40 °C. Physical examination on admission revealed that both cervical lymph nodes were swollen and tender, more obviously so on the lef side. Double lung auscultation detected lower breathing sounds.

Laboratory examinations revealed the following: white blood cell count, 2.45 × 109/l; neutrophils: 48.70%; lymphocytes: 42%; red blood cell count: 3.9 × 1012/l; hemoglobin: 101 g/l; platelets: 141 × 109/l; erythrocyte sedimentation rate: 30 mm/h; procalcitonin: 0.095 ng/ml; and C-reactive protein: 19.11 mg/I. The results for tumor markers, autoimmune antibodies, anti-neutrophil cytoplasmic antibodies and blood cultures were normal. The T-SPOT and purifed protein derivative tests for tuberculosis were negative, as were tests for pleural tuberculosis antibodies. Bone marrow cytological analysis revealed bone marrow hyperplasia.

Computed tomography (CT) of the chest revealed slight swelling of the mediastinal lymph nodes and a small amount of bilateral pleural effusion, which was slightly more severe on the right side (Figure 1). Ultrasonography of the neck revealed multiple swollen bilateral supraclavicular lymph nodes, with some as large as 16 × 7 mm. Ultrasonography of the upper abdomen and uterus did not reveal any anomaly.

Figure 1 Computed tomography of the chest, revealing slight swelling of the mediastinal lymph nodes and a small amount of bilateral pleural effusion, with slightly more on the right side than on the left. 

The pleural puncture technique was applied to drain excessive fuid, and Rivalta test results were positive. The pleural efusion pH was 7.35 (normal, 6.8-7.6), proteins were 32 g/l (normal, 0-30), and lactate dehydrogenase, adenosine deaminase and carcinoembryonic antigen levels were 2186 U/l (normal, 0-200), F30 U/l (normal, 0-40) and 1.64 ng/ml (normal, 0-6.5), respectively. The total number of nucleated cells in the pleural effusion was 3886 × 106/l (normal, 100-500 × 106/l). Repeated pleural fuid cytological analysis revealed a large quantity of lymphocytes. Pleural fuid cultures were negative.

The patient underwent two weeks of anti-infammatory treatment with 0.2% levofoxacin, 300 ml daily administered by means of intravenous drip, which was inefective. She still experienced intermittent fever, and ultrasonography revealed continued pleural effusion.

A biopsy on the lef cervical lymph node showed scattered fbrin deposition, a large amount of nuclear debris and large mononuclear cell aggregates in the necrotic area (Figure 2). The pathological diagnosis was histiocytic necrotizing lymphadenitis.

Figure 2 Biopsy specimen from the left cervical lymph node. Pathological manifestation showing fibrin deposition, a large amount of nuclear debris and large mononuclear cell aggregates within the necrotic regions (hematoxylin and eosin staining; magnification × 400). 

Antibiotics were discontinued afer two weeks of treatment with intravenous infusion of levofoxacin, and 10 mg of oral prednisone was administered three times daily. Within three days, the patient’s body temperature gradually returned to normal. Afer general improvement during a one-week observation period, she was discharged and was prescribed a reduced dose of oral prednisone. Tree months later, a chest radiograph showed that the double lung texture disorder and bilateral pleural effusion had disappeared (Figure 3).

Figure 3 Chest radiograph, showing that the double lung texture disorder and bilateral pleural effusion had disappeared. 

DISCUSSION

Histiocytic necrotizing lymphadenitis is a rare infammatory disease of the lymph nodes. It is more common in young women and has a natural course of 1-4 months,3 but relapse may occur. The cause of HNL remains unclear, but it is probably associated with infections and autoimmune disorders. A variety of viruses, such as adenovirus, Epstein-Barr virus and herpes virus, are reportedly associated with the disease. HNL onset is commonly associated with acute or subacute clinical manifestations, such as swollen lymph nodes, fever and neutropenia. The most commonly afected lymph nodes are cervical, followed by axillary. Intermittent fever, fatigue, joint pain, hepatosplenomegaly and skin rashes are also common symptoms. Rarely, HNL patients exhibit complex clinical manifestations involving multiple organ systems, similar to those for rheumatic diseases.

It has been reported in the literature that the clinical manifestations of HNL are similar to those of certain connective tissue diseases, such as adult-onset Still’s disease and SLE. There are also reports of HNL co-occurring with these diseases, with the strongest link to SLE. Reports have suggested that HNL can occur before, afer or concurrently with SLE pathogenesis.4 In particular, antinuclear antibody-positive HNL is more likely to develop into SLE, and certain scholars even hold that HNL is a unique manifestation of SLE.5 Additionally, certain clinical manifestations of lymphoma are very similar to those of HNL; as such, HNL patients are ofen misdiagnosed as having malignant lymphoma.

Noninvasive diagnostic methods are limited in their efectiveness. At present, application of 18F-deoxyglucose (18F-FDG) positron emission tomography (PET)/CT is widely used as a tumor metabolism imaging technique for determining lymph node malignancy. However, studies using FDG imaging and PET/CT have suggested that in HNL patients, lymph node uptake values ranged from 2.05 to 13.94, with an average of 6.25 ± 3.32. Cervical lymph nodes ofen have a higher uptake value. Evidently, PET/CT scans alone are not sufcient to diferentiate between HNL and lymphoma, but the biopsy site can be determined using the standard uptake value.6

Pathological and immunohistochemical examinations are important tools for diferential diagnosis. In 1995, Kuo7 further defned HNL into three subtypes: proliferative, necrotic and xanthomalike, which may refect the diferent stages of disease development, namely hyperplasia-necrosis-xanthoma or granulation-reabsorption-recovery. The pathological characteristics of HNL include a patchy lymph node disorder, commonly found in the juxtacortical area with visible fbrinoid necrosis and a large amount of nuclear debris. Necrotic areas are surrounded by proliferative cells, but granulocytes and plasma cells are rare or absent. Specialized or tufed CD68-positive and MPO-positive cells are important immunohistochemical features of HNL.8 T-cells are the most commonly found lymphocytes, while B-cells and natural killer cells are rarer. Using an electron microscope, a large number of apoptotic bodies surrounded by mononuclear histiocytes and scattered T-cells undergoing apoptosis were found in the lymph nodes of HNL patients. These three observations are closely related, and they suggest that T-lymphocyte apoptosis may play an important role in the pathogenesis of HNL.9

The incidence of pleural effusion in HNL is low and rarely reported clinically, so we cannot reach any conclusion regarding the likelihood that HNL patients might have pleural effusion. In the present case, the patient had an exudate. The mechanism of its occurrence remains unclear, and it is possible that the disease itself may lead to pleural disruption, thus causing exudative pleurisy; however, there is a lack of histological evidence to support this concept. Pleural biopsies can easily miss the location of the lesion, since they can only collect a relatively small amount of the sample, and they may be prone to false negative results. On the other hand, thoracoscopy or thoracotomy examinations are highly invasive and are not very popular with most patients. Additionally, the possibility that HNL might be caused by an endogenous sex hormone dysfunction cannot be ruled out, since corticosteroid therapy has been observed to lead to complete reabsorption of pleural effusion. The mechanism of pleural effusion in HNL patients still need to be further investigated.

We searched for similar cases in diferent databases (PubMed, Embase and LILACS) using the following terms: “histiocytic necrotizing lymphadenitis” AND “pleural effusion” or “Kikuchi-Fujimoto disease” AND “pleural effusion” (Table 1). We found that only one case had been published.10

Table 1. Results from a search of the literature in medical databases, for case reports on “histiocytic necrotizing lymphadenitis with bilateral pleural effusion diagnosed via cervical lymph node biopsy”. The search 

Database Search strategies Papers found Related papers
MEDLINE (via PubMed) ((histiocytic necrotizing lymphadenitis[Title]) AND pleural effusion[Title]) 0 0
MEDLINE (via PubMed) ((Kikuchi-Fujimoto disease[Title]) AND pleural effusion[Title]) 1 1
Embase (via Elsevier) ((histiocytic necrotizing lymphadenitis[Title]) AND pleural effusion[Title]) 0 0
LILACS (via BVS) ((histiocytic necrotizing lymphadenitis[Title]) AND pleural effusion[Title]) 0 0

The treatments for HNL include non-steroidal anti-inflammatory drugs and corticosteroids; antibiotic treatment is often ineffective. Although non-steroidal anti-inflammatory drugs can elicit partial effects, there have been reports suggesting that this treatment may cause patients to be more prone to relapse.11 It has been suggested that early glucocorticoid therapy should be used to treat HNL, and that the duration and intensity of the treatment should be based on the patient’s response to hormone therapy and the results from follow-up examinations.12

CONCLUSIONS

Pleural effusion is a very uncommon manifestation of HNL that has rarely been reported in these patients. We presented a case of HNL with bilateral pleural effusion that was diagnosed using cervical lymph node biopsy and which was successfully treated with prednisone.

HNL patients are ofen admitted to a respiratory department, and it is easy to misdiagnose them as having tuberculous pleurisy or other diseases. We reported on this patient in order to improve clinicians’ understanding of such diseases and help reduce the likelihood of misdiagnosis.

REFERENCES

1. Chen HC, Lai JH, Huang GS, et al. Systemic lupus erythematosus with simultaneous onset of Kikuchi-Fujimoto’s disease complicated with antiphospholipid antibody syndrome: a case report and review of the literature. Rheumatol Int. 2005;25(4):303-6. [ Links ]

2. Papaioannou G, Speletas M, Kaloutsi V, Pavlitou-Tsiontsi A. Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) associated with antiphospholipid syndrome: case report and literature review. Ann Hematol. 2002;81(12):732-5. [ Links ]

3. Bosch X, Guilabert A, Miquel R, Campo E. Enigmatic KikuchiFujimoto disease: a comprehensive review. Am J Clin Pathol. 2004;122(1):141-52. [ Links ]

4. Santana A, Lessa B, Galrão L, Lima I, Santiago M. Kikuchi-Fujimoto’s disease associated with systemic lupus erythematosus: case report and review of the literature. Clin Rheumatol. 2005;24(1):60-3. [ Links ]

5. Yu HL, Lee SS, Tsai HC, et al. Clinical manifestations of Kikuchi’s disease in southern Taiwan. J Microbiol Immunol Infect. 2005;38(1):35-40. [ Links ]

6. Ito K, Morooka M, Kubota K. Kikuchi disease: 18F-FDG positron emission tomography/computed tomography of lymph node uptake. Jpn J Radiol. 2010;28(1):15-9. [ Links ]

7. Kuo TT. Kikuchi’s disease (histocytic necrotizing lymphadenitis). A clinicopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy. Am J Surg Pathol. 1995;19(7):798-809. [ Links ]

8. Pileri SA, Facchetti F, Ascani S, et al. Myeloperoxidase expression by histiocytes in Kikuchi’s and Kikuchi-like lymphadenopathy. Am J Pathol. 2001;159(3):915-24. [ Links ]

9. Ohshima K, Shimazaki K, Kume T, et al. Perforin and Fas pathways of cytotoxic T-cells in histiocytic necrotizing lymphadenitis. Histopathology. 1998;33(5):471-8. [ Links ]

10. Garcia-Zamalloa A, Taboada-Gomez J, Bernardo-Galán P, et al. Bilateral pleural effusion and interstitial lung disease as unusual manifestations of Kikuchi-Fujimoto disease: case report and literature review. BMC Pulm Med. 2010;10:54. [ Links ]

11. Jun-Fen F, Chun-Lin W, Li L, et al. Kikuchi-Fujimoto disease manifesting as recurrent thrombocytopenia and Mobitz type II atrioventricular block in a 7-year-old girl: a case report and analysis of 138 Chinese childhood Kikuchi-Fujimoto cases with 10 years of follow-up in 97 patients. Acta Paediatr. 2007;96(12):1844-7. [ Links ]

12. Jang YJ, Park KH, Seok HJ. Management of Kikuchi’s disease using glucocorticoid. J Laryngol Otol. 2000;114(9):709-11. [ Links ]

Received: January 23, 2017; Accepted: February 17, 2017

Address for correspondence: Xuchun Liu, Department of Respiratory Medicine, Chizhou People’s Hospital, Chizhou, Anhui 247100, China, E-mail: liuxu0832@sina.com

Conflict of interest: The authors declare that they have no conflict of interest

Creative Commons License This is an open-access article distributed under the terms of the Creative Commons Attribution License