Case Report and Discussion
This study was exempt from review by the UCSF Institutional Review
Board. A 71 year old man presented to clinic with a six month history of
a left-sided soft, compressible neck mass. He denied any associated pain
or dysphagia, compressive symptoms, hoarseness, or globus. His past
surgical history was notable for a childhood adenotonsillectomy;
urothelial carcinoma in situ status post two transurethral
resections of bladder tumors and two therapeutic courses with one
maintenance intravesical immunotherapy with BCG. His treatment was
complicated by BCG cystitis, for which the patient was treated with a
three weeks of isoniazid and rifampin, and his symptoms resolved. The
last intravesical BCG therapy was completed six months prior to
developing a neck mass and 12 months prior to presentation in clinic.
Outside hospital workup of the mass included an ultrasound of the neck
and an MRI. These showed a left level II/III 6.6 x 2.8 cm complex cystic
mass with a mural soft tissue component and an unusually thick
septation. The patient had undergone two fine-needle aspirations, which
yielded purulent material with neutrophils but no observed growth on
bacterial, fungal, and acid-fast bacilli cultures. A multidisciplinary
review of this case favored additional imaging with computed tomography
of the neck and chest (Figure 1). This demonstrated a left lateral neck
non-calcified fluid collection with a thick rim and enhancing internal
septation. There were no associated calcifications, no surrounding
inflammatory changes, and the collection displaced the carotid and
jugular vessels anteriorly. Chest CT revealed calcifications within
mediastinal lymph nodes and spleen, indicating prior granulomatous
infection.
The infectious disease service was consulted for diagnostic workup and
management. QuantiFERON-TB Gold Plus returned negative. The patient also
tested negative for human immunodeficiency virus, which confers a higher
incidence of tuberculous lymphadenitis with
co-infection.4 Additional antibody and antigen testing
for Histoplasma capsulatum , Coccidioides immitis ,Coxiella burnetii , Bartonella and Brucella species
was unremarkable. The patient was started empirically on isoniazid,
rifampin, and ethambutol given high clinical suspicion for disseminated
BCG infection. 16S ribosomal RNA sequencing of FNA specimen ultimately
detected mycobacterium tuberculosis complex. Specimen was sent to
the California State Laboratory for pyrosequencing, which detected DNA
of M. bovis and confirmed susceptibility to isoniazid and
rifampin. On therapy, patient initially experienced paradoxical
worsening of the left neck mass before improvement. At most recent
follow-up in March 2020, the patient had nearly completed planned six
months of antimicrobial therapy with a persistent small area of nodular
hyperpigmentation at the neck mass site.
A parapharyngeal space lesion is a rare complication of BCG treatment
for urothelial carcinoma. Risk of disseminated mycobacterial infection
is increased in individuals with foreshortened time between surgical
treatment and intravesical instillation of BCG. Reported onset of
symptoms can vary from 3 months to 1 year following BCG
treatment.5
Disseminated BCG infections may not require surgical intervention, but
should be treated with extended courses of medical therapy and undergo
surveillance for treatment response. A suggested duration of therapy is
three to six months with a multidrug regimen of rifampin, isoniazid, and
ethambutol. A close review of the patient’s medical history and
exposures is needed to raise suspicion for this rare etiology. Molecular
diagnostics, such as 16S rRNA sequencing, may be key to diagnosis in
cases where serology and culture-based testing is inconclusive.