Prompt suspicion of less frequent opportunistic pathogens could drastically affect outcomes in patients with diffuse large B-cell lymphoma (DLBCL), according to a study recently published in Clinical Hematology International.

“While diarrhea due to direct mucosal toxicity of high dose chemotherapy and neutropenic typhlitis is not uncommon amongst autoSCT patients, persistent and worsening culture-negative diarrhea post engraftment with fever should raise suspicion that something unusual may be amiss,” the authors wrote.

Read more about DLBCL diagnosis

This case report describes a 62-year-old male from Australia, previously diagnosed with small lymphocytic lymphoma (SLL) in 2016. After 4 years of follow-up, a biopsy of a new subcutaneous lesion revealed a DLBCL, composite follicular grade 3A subtype, following a Richter’s transformation. A positron emission tomography/computed tomography (PET/CT) scan further reported various nodes of SLL.

Medical history was significant for trisomy 12, obesity, nonalcoholic fatty liver disease, banded hemorrhoids, chronic left mastoid cavity, and recurrent sinusitis during childhood. The patient also reported a history of smoking.

Therapy with rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone began, as well as prophylactic entecavir. All serum immunoglobulin levels were within normal range. A follow-up PET/CT scan after 3 cycles of chemotherapy demonstrated a germinal center DLBCL, achieving complete remission after treatment with rituximab, ifosfamide, carboplatin, and etoposide.

The patient later underwent an autologous stem cell transplantation and chemotherapy conditioning. On the first postoperative day, he experienced nonbloody diarrhea, followed by absolute neutropenia on the third day and febrile neutropenia on day 4.

Blood and fecal cultures were negative, as well as viral, bacterial, and parasitic PCR. He initiated piperacillin-tazobactam and granulocyte colony-stimulating factor with neutrophil recovery but persistent fever. The healthcare team diagnosed engraftment syndrome and administered prednisolone.

Regardless, diarrhea and fever persisted. A sigmoidoscopy and biopsy did not report abnormalities, and a CT scan revealed multifocal enterocolitis and small bowel dilation, managed with nasogastric and rectal decompression. Nutrition was completely parenteral at this point.

Finally, another colonoscopy showed mucosal ulceration, and a biopsy revealed fungal elements of a ribbon shape. A PCR confirmed the presence of Rhizopus. Unfortunately, a week after, the patient died.

Suspicion of disseminated mycosis, based on clinical evidence, is an important practice among patients with DLBCL, especially since it does not seem to follow a specific pattern of risk factors, the authors noted.

“This case highlights the difficulty in predicting, preventing, and treating invasive mucormycosis in hematology patients outside the usual contexts of GvHD post allograft or prolonged neutropenia during acute leukemia induction treatment,” the study team concluded.


Scheffer E, Reynolds G, Grigg A. Disseminated invasive mucormycosis infection following autologous stem cell transplantation for diffuse large B-cell lymphoma. Clin Hematol Int Published online February 8, 2023. doi:10.1007/s44228-023-00031-z