HISTIOCYTIC NECROTIZING LYMPHADENITIS (KIKUCHI’S – FUJIMOTO

DISEASE) IN AN HIV – POSITIVE FILIPINO MALE PRESENTING AS INGUINAL

LYMPHADENITIS

A Case Report

Submitted to the Philippine College of Physicians Annual Convention Research Contest: 2018

Most Outstanding PCP Researches

By:

Rhaffy B. Rapacon, MD

Year Level 2 Internal Medicine Resident

Department of Internal Medicine

Dr. Pablo O. Torre Memorial Hospital

Histiocytic Necrotizing Lymphadenitis (Kikuchi’s – Fujimoto Disease) in an HIV – Positive
Filipino Male Presenting as Inguinal Lymphadenitis
A case report and review of literature

ABSTRACT

Kikuchi’s – Fujimoto Disease (KFD), also known as Histolytic Necrotizing Lymphadenopathy,

was first described by Kikuchi in 1972 as an unusual lymphadenitis of unknown etiology, which was
more frequent in young women in Japan, with benign self-limiting clinical course. In a Meta-analysis of
181 publications since 1991, there was a reported worldwide incidence of only 244 cases 8. Here we
report a case of Kikuchi-Fujimoto disease in a 25 year old, homosexual Filipino, male presenting as a
painful inguinal lymph node associated with episodes of intermittent fever for two weeks and a diagnosed
case of HIV/AIDS with CD4 count of 39 cells/ microliter.

BACKGROUND

Kikuchi – Fujimoto disease (KFD) is a benign, self –limited, well defined clinico-

pathologic disorder first described by Kikuchi in 1972 and simultaneously, but independently by

Fujimoto in 198711,16. KFD is known to have a worldwide distribution with a higher prevalence

among Japanese and other Asiatic people. The worldwide distribution of KFD is 60% in Asia, 33

% in Europe and 8% in America8. Philippine data regarding this rare disease remains extremely

limited as there are only five published case reports of the disease diagnosed in a Filipino and
1,4,18
they are female . Affected patients most often are adults younger than 40 years with mean
16, 12
age of 25 years old . In general, a female preponderance has been reported with female to
11, 16
male ratio of 4:1 . Kikuchi- Fujimoto Disease is extremely unusual in HIV infected

individuals. The pattern of lymphadenitis seen in KFD is rarely present in HIV-positive patients.

Although diagnosis can be made simply by conventional histomorphology, it may be

misinterpreted as malignant lymphoma or tuberculosis as they are common AIDS- defining

illnesses.
CASE REPORT

In October 2016, a 25-year-old homosexual Filipino male, a health care provider,

diagnosed with Human Immunodeficiency Virus infection two weeks prior with CD4 count of

39 cells/ microliter, came in with a two-week history of painful inguinal lymphadenopathy

associated with fever, 50% weight loss in 12 months, and 2 months’ history of watery, non-

bloody diarrhea. Past medical history was unremarkable. He was a 5 pack year smoker and an

occasional alcoholic beverage drinker. Multiple sexual partners were noted with history of sex

with men started in December 2012. Physical examination revealed Deep, round, subcentimeter,

mobile, non-tender lymph nodes on left supraclavicular area and a 2x2 cm mass, mobile, tender,

round, with regular borders on left inguinal area were palpated. The remainder of the

examination was unremarkable. With this history and physical examination a consideration of

Extrapumonary Tuberculosis Lymphadenitis was entertained thus laboratories were done and

revealed no signs of TB infection.

Computed Tomography of the abdomen with triple contrast was done which shows

slightly enlarged lymph nodes in both inguinal regions, the largest in the left measures 3.2 x 1.2

x 0.7cm while the largest in the right measure 2.1 x 1.6 x 0.8cm. Subcentimeter lymph nodes

were seen in the paraaortic and interaortocaval areas. Subcentimeter to marginal-sized lymph

nodes was also seen in the mesentery, the largest of which measures 1.3 x 0.8cm (Fig 1).

Inguinal Lymph Nodes biopsy revealed negative for AFB, no fungal elements noted on

KOH and Pus cells 5-8/LPF in GS. Partly effaced nodal architecture with sheets of medium-

sized cells with round to oval nuclei, prominent nucleoli and scantly to indistinct cytoplasm with

numerous Tingible body macrophages were noted on microscopy (Fig 2- Fig 4).
 Due to persistence of thrombocytopenia, neutropenia and leukopenia with decreasing

ANC Peripheral Blood smear was done which revealed: consisted with thrombocytopenia.

High grade fever and chronic diarrhea were noted during hospitalization further

investigations were done. Stool exam revealed presence of Salmonella infection and

Cryptosporidium parvum (Modified Kinyoun Test).

Slides were reviewed for immunohistostain at a Tertiary Hospital in Manila and revealed

positive CD68 in histiocytes and Positive Ki-67 in high germinal centers. CD20, CD3, CD10 and

BCL2 were all negative (Table 1). Due to this result a final diagnosis of Kikuchi- Fujimoto

Lymphadenopathy was considered.

Patient clinically improved with supportive treatment and he was discharged with

primary care follow-up. After proving that the disease was not due to tuberculosis an

antiretroviral therapy was started and currently resumes his activities of daily living. Follow up

CT scan three months after being discharged was done and showed interval regression of

bilateral inguinal lymphadenopathy.The largest inguinal lymph node in the left now measures 1.8

x 1.1 x 0.6cm (previously 3.2 x 1.2 x 0.7cm). The largest in the right now measures 1.6 x 1.1 x

0.6 cm (previously 2.1 x 1.6 x 0.8 cm). Regression of subcentimeter to marginal sized

reptroperitoneal and mesenteric lymph nodes was also noted. The largest in the right now

measures 1.6 x 1.1 x 0.6 cm (previously 2.1 x 1.6 x 0.8 cm). The largest inguinal lymph node in

the left now measures 1.8 x 1.1 x 0.6cm (previously 3.2 x 1.2 x 0.7cm).

DISCUSSION:

In 1972, Kikuchi and Fujimoto described a rare benign, self –limited, systemic

lymphadenitis, well defined clinicopathologic disorder called Histiocytic Necrotizing

Lymphadenitis. This pattern of lymphadenitis is rarely present in HIV-positive patients 4. It has

a worldwide distribution with a high prevalence among Japanese and other Asiatic people and it

usually has a female preponderance of 4:1. It affects adults under 40 years old, mean age of

which is 25 years old. Fever may be present in 30-50% of the cases. An unusual location of

lymph node involvement can make the diagnosis of Kikuchi’s disease difficult.

Lymphadenopathy (56-98%) is more frequently cervical (70-80%), but some authors report

generalized lymph node enlargement (1.3-22.2%). Painful lymphadenopathy is seen in up to

59% of patients 7, 16. Lymph node size ranges from 0.5 to 4 cm (93.4%), and occasionally, lymph

nodes are larger than 6 cm 7. Our patient is a male, presented as painful left inguinal lymph nodes
7
largest was 3.2 x 1.2 x 0.7 cm, which described in one study as a rare site of occurrence.

Localization of Kikuchi’s disease to the mesenteric lymph nodes is quite unusual. Only eight
10
cases have been previously described in the medical literature . Mesenteric involvement was

noted in the CT scan of our patient. Subcentimeter lymph nodes in the paraaortic and

interaortocaval areas was also noted, in my review of literature there is no study that mentioned

such involvement. Mild leukopenia has been observed in 25% to 58% of patients, whereas

leukocytosis is found in 2% to 5% of cases. Moreover, 25% to 31% of patients have atypical

16, 14
peripheral blood lymphocytes . In the case of our patient serial monitoring of complete

blood count was done and revealed presence of leukopenia and atypical reactive lymphocytes

which them improves after giving one dose of Filgrastin.

The pathogenesis for KFD has been hypothesized as either viral or autoimmune in

etiology. A viral infection is possible by virtue of clinical manifestations. Among others, EBV

and herpesviruses 6 and 8 have been suggested as potential causative agents of KFD. With

regard to EBV, there are 2 studies that detected EBV by means of in situ hybridization for EBV-
encoded RNA expression. However, there have been several other studies that attempted to

localize the virus genome have concluded that neither EBV nor herpesvirus 6 or herpesvirus 8

has a putative role in the pathogenesis of KFD4, 16. Morphology is similar to lupus erythematosus

lymphadenitis; a relationship between these two processes has been debated 4.

Definitive Diagnosis depends on histopathologic examination of the lymph nodes

showing paracortical Necrosis (patchy or confluent), Histiocytes with cresentric nuclei,

19
Lymphocytes, plasmatoid monocytes, immunoblasts and karyohexis . Significant absence of

Neutrophils and eosinophil, with absent or sparse plasma cells is one of the characteristic of

KFD. Three phases were described in the literature by histology over the course of the disease:

the proliferative phase (follicular hyperplasia with paracortical expansion), the necrotizing phase

(paracortical necrosis, karyorrhexis and hystiocytic predominance) and the xanthomatous phase
9, 17
(resolution of necrosis) . Immunohistochemical stains show CD68 positive plasmacytoid

monocytes and histiocytes with predominantly CD8 positive T lymphocytes 9 and positive in Ki

67 (increased mitotic index) 4. Necrotizing phase fits in our patient histopathologic description

and the large prevalence of histiocytes was confirmed by immunohistochemical staining showing

CD68 Positive cells and increased mitotic index showing Ki67 possitive. Table 2 shows a

Diagnostic Criteria for Kikuchi–Fujimoto Disease according to Deaver et al 2.

In HIV positive patients, Necrotizing lymphadenitis is frequently associated with

4,
mycobacterium infection thus proper diagnostic procedure to rule out this infection is

necessary to avoid aggressive and unnecessary therapy. Lymphadenopathy runs a benign course

and appears to resolve spontaneously even without any therapy after 1 to 6 months after definite

diagnosis 3, with 4 % recurrence rate. In one study entitled CT Findings in Kikuchi Disease:

Analysis of 96 Cases shows that Follow-up CT in 32 patients showed complete resolution in 14

 15
and partially improved lymphadenopathy in 18 of cases . In our patient repeat CT scan after

3months showed interval regression of bilateral inguinal lymphadenopathy even without

treatment. Currently patient went back to his activities of daily living and now maintained on

antiretroviral drugs.

CONCLUSION:

Although rare it is important to diagnose KL in HIV- Infected individuals as a distinctive

clinical-pathologic process. We should always consider it on the list of differentials especially in

young, male with lymphadenopathy. Kikuchi’s lymphadenitis is a diagnosis that can only be

made by biopsy and histology findings. It is self-limited and has good prognosis. Proper

identification of histologic finding by clinicians and pathologist will help to avoid unnecessary

and sometimes harmful treatment.

FIGURES:

Fig.2. Microscopy. Sections from the case we

have defined vari-sized germinal center
Fig. 1 Abdominal CT scan with Triple Contrast. follicle bounded by distinct mantle zone and
Subcentimeters to marginal-sized lymph nodes fairly equally spaced follicles.
are seen in the mesentery, the largest of which
measures 1.3 x 0.8cm. (A) Slightly enlarged
lymph nodes in both inguinal regions, the largest
in the left measures 3.2 x 1.2 x 0.7cm (B) and
the largest in the right measure 2.1 x 1.6 x
0.8cm(C)
 Fig 6. Microscopy: Higher magnification show
Fig.5.Microscopy: Widened para-follicular increased mitotic activity at the germinal
area that suggests effacement center with 4 mitotic figures seen in one field

TABLE: 1: Immunohistochemical stain Results TABLE: 2 Diagnostic Criteria for Kikuchi–

Fujimoto Disease according to Deaver et
al.
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