Keywords basidiobolomycosis - gastrointestinal - Sudan
Introduction and Summary of Cases
Gastrointestinal infection with basidiobolomycosis is due to ingestion of contaminated
food.[1 ] The most common presenting feature is vague abdominal pain sometimes associated
with diarrhea or constipation.[2 ] Most patients are usually immunocompetent and they present with features of acute
appendicitis or features of intestinal obstruction mimicking cancer.[3 ]
[4 ]
[5 ]
[6 ]
[7 ]
[8 ] The diagnosis is based on histological examination of a deep biopsy from the affected
site. The treatment is a combination of antifungal drugs and surgery.[3 ]
[4 ] All our patients, except for the patient with features of acute appendicitis, underwent
resection surgery due to suspicion of a mass. Therefore, cultures were not obtained
as the surgical teams’ initial diagnosis was malignancy and all specimens were received
fixed in 10% buffered formalin. The seven samples of the cases were obtained from
the period of December 2017 and December 2018 (five specimens were sent to Khartoum
Histocenter and two specimens to Khartoum Soba University Hospital Laboratory). From
the paraffin-embedded blocks, hematoxylin and eosin stained sections were done and
examined under light microscope. Periodic acid-Schiff and Grocott silver stains were
used to highlight the fungal hyphae and zygospores.[5 ] Among the seven patients, three were children, presented with abdominal mass, rectal
bleeding, and features of acute appendicitis. The remaining four patients were adults
three of them were males and one female, two presented with abdominal pain, one with
a stenotic mass at the ileocecal junction, and two were known to have diabetes. Radiology
revealed mural thickening of the bowel wall with stenosis. All patients underwent
surgery due to suspicion of malignancy except for the child who presented with symptoms
of acute appendicitis. The bowel specimens were characterized by marked thickening
of the wall with fibrosis. Histologic examination showed transmural prominent tissue
eosinophil infiltration and granulomatous inflammation around pale fungal hyphae extending
to the mesenteric fat sparing the mucosa. Importantly, the seven patients received
antifungal treatment and five of them recovered except two adult males died. Two patients
in this case series received itraconazole for the first 2 months with no clinical
improvement and showed better response to voriconazole. The clinical, laboratory,
and surgical features of all patients are presented in [Table 1 ]. All patients have signed the written consent for publication.
Table 1
Clinicopathologic features of patients with gastrointestinal basidiobolomycosis
Case
Age (y)
Sex
Symptoms
WBC ×10/mm3
Eosinophils %
ESR mm/h
Radiological findings
Clinical diagnosis
Treatment
Follow-up
Abbreviations: ESR, erythrocyte sedimentation rate; F, female; M, male; NA, not available;
WBC, white blood cell.
1
53
M
Abdominal pain
16.4
Not done
90
Cecal mass
Colonic carcinoma
Right hemicolectomy + voriconazole orally
Died
2
17
F
Abdominal mass
NA
NA
NA
Thick large bowel wall
Lymphoma
Transverse colectomy + voriconazole orally
Well
3
13
M
Constipation and bleeding per rectum
NA
NA
NA
Rectal mass
Limited rectal resection
Well
4
56
F
Abdominal pain and fever
NA
NA
NA
Perforated appendix and cecal mass
Colonic carcinoma
Right hemicolectomy + voriconazole
Died
5
58
M
Intestinal obstruction
NA
NA
NA
Sigmoid mass
Colonic carcinoma
Sigmoid colectomy
Well
6
50
M
Abdominal pain
NA
NA
NA
Cecal mass
Colonic carcinoma
Right hemicolectomy
Well
7
6
F
Right iliac fossa mass
17.91
1
30
Thickening of transverse colon wall
Appendicitis
Appendectomy + voriconazole
Well
Case 1
A 53-year-old male from Al-Jazeera state (central of Sudan) known to have diabetes
and hypertension, presented complaining of abdominal pain and right lower quadrant
swelling for 1 month. Ten days before hospital admission, he was diagnosed as a case
of appendicular mass and treated conservatively. Abdominal examination showed mildly
distended abdomen with a visible mass in the right iliac fossa. Computed tomography
(CT) abdomen showed diffuse circumferential wall thickening of the cecum with surrounding
fat stranding, mild ascites, but no para-aortic lymph nodes enlargement. This was
thought to be highly suggestive of cecal malignant tumor with subacute bowel obstruction.
Therefore, he was treated surgically (right hemicolectomy) without blood culture,
colonoscopy, and biopsy. During surgery he was found to have cecal mass measuring
8 × 7 cm fixed to the posterior abdominal wall. Importantly, histopathology result
showed basidiobolomycosis and he was immediately started on antifungal treatment (voriconazole).
He developed pulmonary edema and died.
Case 2
A 17-year-old female presented with vague abdominal pain. Clinical examination revealed
an abdominal mass. CT scan showed multifocal omental thickening and thick wall bowel
loops. The working diagnosis was lymphoma/abdominal tuberculosis (TB). Omental biopsy
was taken and showed basidiobolomycosis. The patient was referred for surgical excision
of mass. Transverse colon with adherent omentum was resected. Cut surface of colon
shows circumferential thickening of the wall and serosa with homogenous white appearance.
Histopathology showed circumferential inflammatory mass composed of mixed inflammatory
infiltrate composed of eosinophils, neutrophils, and multinucleated giant cells surrounding
broad fungal hyphae and zygospores. She was successfully treated with voriconazole
as she did not show improvement with itraconazole.
Case 3
A 13-year-old male presented with relative constipation, bleeding per rectum for 1
week. Examination revealed a 4-cm rectal mass. Rectal biopsy showed basidiobolomycosis.
He was commenced on itraconazole and then switched to voriconazole. Limited rectal
resection and resected colon showed stenosis and thickening of bowel wall. He was
successfully treated with prolong course of voriconazole.
Case 4
A 56-year-old female known to have diabetes initially diagnosed as intra-abdominal
sepsis. She underwent exploratory laparotomy which revealed perforated appendix and
a mass at the base of the cecum with perforation and enlarged mesenteric lymph nodes.
Therefore, she underwent appendectomy and right hemicolectomy. Grossly inspection
showed thickened wall of the cecum. Histopathology showed surface ulceration and transmural
inflammation of appendix and presence of fungal hyphae surrounded by mixed infiltration
of neutrophils and granulomatous inflammation with marked infiltration of eosinophils.
The ileocecal valve and omentum were also involved. She was commenced on voriconazole,
but sadly the patient did not survive.
Case 5
A 58-year-old male presented with symptoms of intestinal obstruction. Colonoscopy
showed sigmoid mass and biopsy showed granuloma of schistosomiasis. Laparotomy showed
a tumor involving the sigmoid, descending and part of the transverse colon, cecum,
and terminal ileum, and this was treated with right hemicolectomy. Cut surface of
colon showed white tumor involving the ileocecal junction with ulceration of the mucosa
and presence of basidiobolomycosis. The patient recovered well.
Case 6
A 50-year-old male presented with cecal mass. Working diagnosis was malignant neoplasm,
so right hemicolectomy was performed with ileotransverse anastomosis. The cut surface
of the cecum showed diffuse wall thickening with focal area of necrosis and presence
of basidiobolomycosis and made full recovery.
Case 7
A 6-year-old female presented with right iliac fossa pain. Appendectomy was performed
as initial diagnosis was acute appendicitis. Appendix measuring 3.5 × 2 × 1 cm cut
surface show thickened wall. Histology of appendix showed transmural eosinophil and
giant cell inflammatory infiltrate extending into periappendiceal adipose tissue.
Patient was offered right hemicolectomy as she showed no response to antifungal treatment.
Discussion
Basidiobolomycosis is a fungal infection caused by Basidiobolus ranarum . It belongs to the class Zygomycetes. The Zygomycetes includes two fungal orders:
Mucorales and Entomophthorales. The Mucorales cause infection in immunocompromised
patients and include Mucor species and Entomophthorales which affect immunocompetent
individuals and include B. ranarum .[4 ]
[5 ] Basidiobolus species is a fungus found in soil and decaying vegetables and also
in the intestines of some animals like fish and is endemic in tropical parts of Asia
and Africa.[6 ]
[7 ]
[8 ]
[9 ]
[10 ]
[11 ]
[12 ]
[13 ]
[14 ] It is well known to cause subcutaneous involvement and it may leads to subcutaneous
nodules, lymphedema, and hyperpigmentation in the extremities, buttocks, and back.[4 ] Most subcutaneous cases are contracted through minor trauma to the skin or a bite
of an insect.[10 ] The first case of subcutaneous mycosis caused by B. ranarum was reported in 1956 in Indonesia.[4 ] In addition, a few orbitofacial cases has been reported.[15 ]
Infection of the gastrointestinal tract is rare and is mostly acquired by ingestion
of contaminated food, the organism being a vegetable saprophyte. To date, less than
80 cases have been reported worldwide in both children and adult. Most of the cases
were reported from Saudi Arabia, United States, and Iran.[4 ] The first case reported as gastrointestinal basidiobolomycosis was in 1964 in a
6-year-old Nigerian boy.
It can affect any part of the gastrointestinal tract including the stomach, duodenum,
pancreas, liver, terminal ileum, cecum, ascending colon, transverse colon, rectum,
and biliary system. The site of involvement in most of our cases occurred at the ileocecal
junction.[4 ]
Gastrointestinal basidiobolomycosis affects males more than females and can affect
adults and children.[5 ] The clinical presenting features are nonspecific. Abdominal pain and fever are most
common presenting features.[6 ] Other symptoms reported in the literature include constipation, rectal bleeding,
abdominal distension, intestinal obstruction, fever, sweats, diarrhea, memory loss,
and rectal pain.[1 ]
[4 ] Complete blood count usually shows leukocytosis, striking eosinophilia, and high
erythrocyte sedimentation rate.[1 ] Owing to the vague complaints, the provisional diagnosis included inflammatory bowel
disease, TB, malignancy, and appendicitis or appendicular mass.[15 ] Ultrasound and CT scan showed colonic mass[7 ]
[9 ]
[10 ] ([Figs. 1 ]
[2 ]). Most cases underwent endoscopic biopsies none of which reached the correct diagnosis.[5 ] The diagnosis is made by histologic examination of the resected bowel ([Figs. 3 ]
[4 ]).[1 ]
[13 ] Definitive diagnosis is by isolating the organism by inoculation of fresh surgical
specimen on Sabouraud agar. Specific serologic immunodiffusion tests are also available.[2 ]
[7 ]
[9 ] Polymerase chain reaction has been used recently to diagnose gastrointestinal basidiobolomycosis
and it showed high sensitivity and specificity but still not widely used due to the
rarity of the disease.[4 ] Resected intestinal specimens are characterized by marked mural thickening with
fibrosis[13 ]([Fig. 2 ]).
Fig. 1 Computed tomography (CT) abdomen shows diffuse circumferential wall thickening of
the right (RT) colon and cecum with surrounding fat stranding.
Fig. 2 Gross morphology showed thick bowel wall with stenotic mass.
Fig. 3 Histology of the resected bowel shows broad fungal hyphae surrounded by marked eosinophil
infiltrate and giant cells. Splendore–Hoeppli reaction is noted. Hematoxylin and eosin
(H&E) ×40.
Fig. 4 Left: Periodic acid-Schiff (PAS) stain. Right: Grocott-Gomori’s Methenamine Silver
(GMS) stain both highlight the broad fungal hyphae.
On histopathologic examination, the characteristic morphologic features were transmural
inflammatory infiltrate with peritoneal involvement sparing the mucosa consisting
of granulomatous inflammation around fungal hyphae. The inflammatory infiltrate mostly
consists of eosinophils, microabscesses, and giant cells. The fungal hyphae are irregular
and thin walled, sometimes aggregated zygospores are seen. Splendore–Hoeppli phenomena
are sometimes noted around fungal hyphae[2 ]
[15 ] ([Figs. 3 ]
[4 ]). Combined surgery of the affected bowel and antifungal treatment for at least 6
months is recommended and gives better results than drugs alone.[6 ]
[11 ]
[15 ] Itraconazole and voriconazole are the most common antifungal agents used.[1 ] Potassium iodide has been used successfully for treatment of subcutaneous basidiobolomycosis
but not gastrointestinal basidiobolomycosis.[10 ] Basidiobolomycosis has a good prognosis.[11 ]
Conclusion
Gastrointestinal basidiobolomycosis is a rare fungal infection that affects both adults
and children with male predominance. The most common presenting features were abdominal
pain. Patients were operated on for suspicion of malignancy. Diagnosis can be challenging
due to the nonspecific clinical presenting features; in addition, superficial intestinal
mucosal biopsies can show nonspecific chronic inflammation. A combination of surgery
and antifungal drugs is the treatment of choice. The prognosis is generally good.[2 ]
