zygomycosis is an uncommon but often fatal opportunistic fungal infection that occurs in the setting of hematologic malignancies , chemotherapy - induced neutropenia , hematopoietic stem cell transplantation , immunosuppressive therapies , diabetes mellitus , and solid organ transplantation [ 1 , 2 , 3 , 4 , 5 , 6 ] .
infection caused by mucorales is called zygomycosis . the members of mucoraceae , which include rhizopus , rhizomucor , mucor , and absidia , cause the vast majority of zygomycosis . 
 zygomycetes are ubiquitous in nature .
spores are released into the air , rapidly germinate , and gain entry through inoculation of respiratory mucosa , skin , or gastrointestinal ( gi ) tract , ultimately causing angioinvasion ( leading to hematogenous dissemination ) , thrombosis , infarction , and necrosis [ 2 , 8 ] .
the main manifestations of disease include rhinocerebral , pulmonary , cutaneous / subcutaneous , and disseminated diseases , with the first two being the most common forms of infection [ 2 , 8 ] .
gi infection is relatively uncommon , but gastric [ 5 , 6 ] , small bowel , ileocecum [ 4 , 10 ] , colon , or liver   involvement has been reported . a case of primary gi zygomycosis due to absidia spp .
gi zygomycosis typically presents with nonspecific symptoms , including abdominal pain , nausea , dyspepsia , vomiting , bloody diarrhea , upper gi bleeding , abdominal distension , intestinal obstruction , and perforation peritonitis [ 5 , 6 , 10 ] , making early antemortem diagnosis very difficult . as such
a high index of suspicion is required for early diagnosis , especially in the presence of predisposing conditions , such as hematologic malignancies , neutropenia , diabetes mellitus , and immunosuppressive therapies [ 1 , 2 , 3 , 4 , 5 , 6 ] .
we report a case of disseminated appendiceal zygomycosis in a neutropenic patient who initially presented as acute appendicitis during induction chemotherapy for acute myeloid leukemia ( aml ) and highlight features that may lead to earlier diagnosis . to our knowledge , appendiceal zygomycosis due to absidia spp . mimicking acute
a 63-year - old woman with relapsed aml and diabetes mellitus was admitted for induction chemotherapy with cytarabine and clofarabine as part of the management plan for allogeneic stem cell transplantation .
she was found to have clostridium difficile infection , and oral metronidazole treatment was started .
an abdominal and pelvic computer tomography ( ct ) scan showed a segmental hypoenhancing area in the mid appendix with minimal surrounding fat stranding concerning for appendicitis .
given the patient 's high risk of perioperative morbidity and mortality , she was initially treated with broad - spectrum intravenous antibiotics consisting of meropenem .
however , her right lower quadrant abdominal pain continued and she developed localized peritoneal signs .
a repeat ct scan obtained 3 days later showed stable inflammation of the appendix with a new finding of an adjacent loop of small bowel with thickened wall .
since the patient was not responding to medical therapy , she was taken urgently to the operating room for an appendectomy for treatment of acute appendicitis .
upon inspection of the right lower quadrant , the appendix was found to be completely necrotic down to the base .
the necrotic appendix was lying on top of an adjacent loop of terminal ileum that was also segmentally necrotic at the contacting surface ( fig .
2 ) . the case was converted to open in order to perform an ileocecectomy with primary stapled anastomosis .
the fascia was closed but the skin was left open to heal by secondary intention due to the infected wound classification .
the patient was admitted to the intensive care unit postoperatively and extubated on postoperative day ( pod ) 1 . despite empiric broad - spectrum antimicrobial therapy with meropenem , linezolid , and fluconazole ,
a ct scan of the chest showed numerous peripheral cavitary lesions that were either septic emboli or fungal infection .
hematoxylin and eosin ( h&e)-stained sections showed ischemic changes , hemorrhage , and thrombosed vessels filled with broad irregular aseptate hyphae ( fig .
gomori methenamine silver ( gms)-stained sections also demonstrated characteristic wide ribbon - like aseptate hyphae that branch at wide angles , typical of zygomycetes , involving both vessels and adjacent submucosa ( fig .
3c ) as well as invading through the muscularis propria of the appendix ( fig .
antifungal therapy was immediately switched to amphotericin b. on pod6 , fungal overgrowth was found in the surgical wound .
the patient 's clinical condition continued to worsen with severe hypotension that required increasing doses of vasopressors . given the patient 's dismal prognosis of surviving such an overwhelming systemic fungal infection , goals of care were transitioned to comfort and she expired on pod8 .
we report an unusual presentation of disseminated gi zygomycosis initially presenting as acute appendicitis in a neutropenic patient with relapsed aml . to our knowledge , appendiceal zygomycosis due to absidia spp . mimicking acute
absidia spp . is ubiquitous in nature and found in soil , decaying organic matter , cotton , and many different grains , seeds , and nuts .
it is a rare pathogen of the order mucorales , accounting for only 23% of all zygomycete infections , and shows almost no pathogenicity in immunocompetent hosts .
infections with absidia spp . usually occur in immunocompromised hosts , including leukemia or lymphoma patients , especially in the setting of chemotherapy - induced neutropenia and broad - spectrum antibiotics [ 11 , 12 ] .
although 7% of all zygomycete infections are known to involve the gi tract , zygomycosis due to absidia spp .
( absidiomycosis ) is extremely rare in these sites , even in patients with leukemia or lymphoma .
several disseminated infections with absidia spp . have been reported , including a case of brain abscess following bone marrow transplantation   as well as a case of metastatic carcinoma with disseminated zygomycosis involving the brain , lungs , and heart . although it involved a different member of mucoraceae , one case of zygomycosis caused by mucor indicus , presenting as an appendiceal mass with spread to the liver ,
the diagnosis of zygomycosis requires demonstration of characteristic wide ribbon - like aseptate hyphae that branch at wide angles ( 4590 ) , especially with fungal specific stains such as gms stain , and should be supported by culture .
vascular invasion resulting in thrombus formation with infarction , necrosis , and hemorrhage is the most characteristic feature of zygomycosis .
disseminated zygomycosis rapidly invades vessels to spread to multiple organs , most frequently involving the lung [ 2 , 3 ] .
successful treatment of zygomycosis has been attributed to early diagnosis , aggressive surgical intervention with resection of the involved tissue , and antifungal therapy with amphotericin b .
since surgery is most effective in the setting of localized disease without dissemination , early diagnosis is crucial in reducing the high mortality associated with zygomycosis .
pathology of the resected ileocecectomy specimen played a crucial role in diagnosing zygomycosis in this case , leading to the initiation of amphotericin b as the appropriate antifungal therapy .
however , the patient developed fatal disease with evidence of dissemination to the lung and abdominal surgical wound at the time of diagnosis . in conclusion , a diagnosis of a fungal infection , including zygomycosis , should be considered in all chemotherapy - induced neutropenic patients who present with symptoms of acute appendicitis .
this is further supported by a previous study reporting that immune defects , especially absolute neutrophil count < 1,000/l , is a major risk factor for the development of fungal disease .
a high index of clinical suspicion with prompt histologic and culture diagnosis of zygomycosis may lead to earlier surgical and/or antifungal treatment that can potentially reduce the high mortality and morbidity associated with gi zygomycosis .
since the patient died , written informed consent was obtained from her next of kin for publication of this case report and any accompanying images .
 zygomycosis is a rare invasive opportunistic fungal infection that occurs in the setting of hematologic malignancies , chemotherapy - induced neutropenia , and immunosuppressive therapies . 
 we report the first case of disseminated appendiceal zygomycosis due to absidia spp . in a neutropenic patient who initially presented as acute appendicitis . a 63-year - old woman with acute myeloid leukemia presented as acute appendicitis 
 while receiving induction chemotherapy and ultimately succumbed to overwhelming disseminated zygomycosis . 
 initial symptoms included loose stools and right lower abdominal pain unresponsive to broad - spectrum antibiotics . 
 clinical examination and cross - sectional imaging suggested acute appendicitis . 
 the final diagnosis was established by histological evaluations of the ileocecectomy specimen , which showed angioinvasive fungal organisms within the necrotic appendiceal wall with characteristics typical of zygomycetes . 
 fungal cultures demonstrated absidia spp . 
 the patient was treated with amphotericin b but expired in the setting of fungal sepsis . 
 a diagnosis of a fungal infection , including zygomycosis , should be considered in all chemotherapy - induced neutropenic patients who present with symptoms of acute appendicitis . 
 a high index of clinical suspicion with prompt histologic and culture diagnosis of zygomycosis may reduce the high mortality and morbidity associated with zygomycosis of the gastrointestinal tract . 