The first suspected disseminated Hormographiella aspergillata infection in China, diagnosed using metagenomic next-generation sequencing: a case report and literature review

Figures & data

Figure 1. Clinical course of the 41-year-old female patient with a disseminated Hormographiella aspergillata infection.

Figure 2. Contrast-enhanced CT showing a pulmonary mass in the left upper lobe invading the left subclavian artery. CT angiography (A) showing the left subclavian artery stenosis (white arrow) and occlusion (red arrow). CT image of the coronal view (B) showing a mass in the left apex of the lung (white arrow) extending into the left subclavian artery. CT images of the lung window (C) and soft tissue window (D) revealed patchy consolidation in the left apex of the lung (red arrow).

Figure 3. Cutaneous lesions evolution throughout disease progression. A: Onset of red papules located on the medial left forearm. B, C: Development of purplish-red plaques and subcutaneous nodules on the left forearm, left anterior chest wall, and left upper back. D: Appearance of erythematous subcutaneous nodules on the inner left forearm. E, F: Presence of a purpuric plaque with necrotic centre on the left forearm. G: Erythematous subcutaneous nodule on the left anterior chest wall.

Figure 4. Macroscopic and microscopic characteristics of Hormographiella aspergillata. A: Skin tissue cultures on two Sabouraud dextrose agar (SDA) slopes both yielded multiple white, cotton-like, dense pure colonies after seven days of incubation at 25°C. B: White cotton-like colonies on an SDA plate after 10 days of incubation at 35°C. C: Lactophenol cotton blue mount of H. aspergillata slide culture showing branched, septate hyphae with cylindrical arthroconidia accumulating around the conidiophore (original magnification ×400).

Figure 5. Histological examination of cutaneous Hormographiella aspergillata infection. A: Intravascular thrombosis in both dermal and subcutaneous vessels. (original magnification ×20, haematoxylin and eosin stain). B: Fibrin thrombus in the dermal blood vessels. (original magnification ×400, haematoxylin and eosin stain). C: Branched septate hyphae embedded in fibrin thrombi in the vessels (original magnification ×600, Grocott-Gomori methenamine silver stain).

Table 1. Characteristics of invasive Hormographiella aspergillata infection in patients with haematological malignancies.

Case	Year/ References	Age/Sex	Country	Underlying disease	Prophylaxis antifungal	Mycological findings	Infection site	Surgery	Antifungal agents	Neutrophil recovery	Outcome
1	1997[6]	24/M	Netherlands	relapsed ALL, HSCT	NO	lung autopsy (histology + culture)	lung	NO	AMB-ITC	NO	died
2	1997[7]	40/F	Germany	relapsed ALL, HSCT	NO	BALF (DE + culture) lung autopsy (histology + culture)	lung	NO	AMB	NM	died
3	2002[8]	34/F	Netherlands	NHL	NO	lung biopsy (DE + culture)	lung	NO	AMB	YES	alive
4	2005[9]	34/M	Belgium	relapsed AML, HSCT	NO	BALF (DE + culture), lung autopsy (histology)	lung	NO	CAS	NO	died
5	2009[10]	14/F	The United States	relapsed AML, HSCT	NO	skin biopsy (culture)	skin, lung brain	NO	VRC-POS-POS + CAS-AMB + CAS	NO	died
6	2011[11]	41/F	Switzerland	AML, HSCT	NO	lung, eye, brain autopsy (NM) blood autopsy (culture)	lung, eye, brain	NO	VRC-POS-CAS	NO	died
7	2011[11]	63/F	Switzerland	AML	NO	lung biopsy (histology + culture)	lung	pulmonary nodules resection	VRC-POS-AMB-VRC	NO	died
8	2011[11]	55/M	Switzerland	relapsed AML, HSCT, IA	NO	lung biopsy (Histology + culture)	lung	pulmonary wedge resection	AMB-VRC	NO	died
9	2011[12]	23/F	France	BAL	NO	lung biopsy (DE + histology + culture)	lung	NO	CAS-VRC-AMB	YES	alive
10	2011[12]	27/M	France	ALD, HSCT	NO	lung autopsy (histology + culture)	lung	NO	CAS -AMB	NO	died
11	2012[13]	25/F	France	ALL	NO	lung biopsy (culture)	lung	NO	CAS -VRC-AMB	NM	alive
12	2013[14]	61/F	Austria	relapsed AML, HSCT	NO	skin biopsy (histology + culture)	skin, lung	skin lesion resection	CAS-AMB + CAS-AMB + VRC	NO	died
13	2015[16]	19/M	France	AML	CAS prophylaxis	sinus biopsy (histology + FFPE PCR)	skin, sino-orbito-cerebral	sinusal debridement	POS-AMB-AMB + VRC	NO	died
14	2015[15]	52/F	The United States	AML	VRC prophylaxis	BALF (NM)	lung	NO	AMB	NM	died
15	2016[17]	51/M	Japan	MDS, HSCT	ITC prophylaxis	lung biopsy (histology + culture), small intestine, lung and brain autopsy (histology)	lung, brain, small intestine	NO	AMB-AMB + CAS- VRC + MCF-AMB + VRC	NO	died
16	2017[18]	36/M	France	AML, HSCT	NO	lung biopsy (histology + fresh tissue PCR) culture negative	lung	pulmonary nodules resection	VRC-AMB	NM	alive
17	2019[19]	54/M	The United States	relapsed CML, HSCT,	NO	BALF (culture), lung, brain autopsy (histology + FFPE PCR)	lung, brain	No	MCF	NM	died
18	2020[20]	66/F	Colombia	relapsed AML	POS prophylaxis	lung biopsy (histology + culture)	lung	pulmonary resection	AMB + CAS-VRC	Yes	died
19	2020[21]	70/M	France	AML, HSCT	NM	BALF (DE + PCR) culture negative	lung	No	AMB	NM	died
20	2021[22]	46/M	Switzerland	AML	POS prophylaxis	lung biopsy (tissue PCR) culture negative	lung	pulmonary resection	AMB-VRC	YES	alive
21	2021[22]	70/F	Switzerland	AML	FLC prophylaxis	lung muscle abscess biopsy (histology + PCR + culture)	lung, gluteus muscle	pulmonary resection	POS-VRC	NM	alive
22	2022[23]	13/F	Korea	relapsed ALL, HSCT	NO	lung biopsy (histology + PCR) culture negative	lung	No	CAS-AMB-AMB + VRC	NM	died
23	2022 present case	41/F	China	relapsed AML, HSCT	POS prophylaxis	skin biopsy (mNGS + histology + culture) BALF (mNGS + PCR) blood (mNGS + PCR)	Skin, Lungs	No	AMB-AMB + VRC	NO	died

M, male; F, female; ALL, acute lymphoblastic leukaemia; HSCT, haematopoietic stem cell transplantation; AML, acute myeloblastic leukaemia; NHL, non-Hodgkin lymphoma; IA, invasive aspergillosis; BAL, biphenotypic acute leukaemia; ALD, adult-onset X-linked adrenoleukodystrophy; MDS, myelodysplastic syndrome; DE, direct microscopic examination; NM, not mentioned; BALF, bronchoalveolar lavage fluid; FLC, fluconazole; ITC, itraconazole; VRC, voriconazole; POS, posaconazole; CAS, caspofungin; MCF, micafungin; AMB, amphotericin B.

Table 2. Antifungal susceptibility profile of Hormographiella aspergillata clinical isolates.

			MIC (μg/ml)
Isolate	Year/ Ref	Method	FLC	ITC	VRC	POS	ISA	CAS	ANF	MCF	AMB
1	1997 [6]	Broth macrodilution	>64	8	/	/	/	/	/	/	0.5
		Agar incorporation	>64	32	/	/	/	/	/	/	0.03
2	2005 [9]	E-test	/	2	0.25	/	/	/	/	/	0.5
3	2009 [10]	BMiD CLSI M-38A2	/	/	0.25	0.5	/	>4	/	/	4
4	2011 [11]	E-test	256	/	0.125	trailing growth	/	32	/	/	0.5
5	2011 [11]	E-test	­/	/	0.125	2	/	/	/	/	0.5
6	2011 [11]	E-test	>256	/	0.25	trailing growth	/	>32	/	/	0.5
7	2011 [12]	BMiD EUCAST	64	≧8	1	/	/	2	/	/	2
8	2013 [14]	E-test	>256	/	0.125	0.064	/	/	/	/	0.094
9	2016 [17]	NM	4	0.25	0.015	/	/	/	/	>16	0.125
10	2019 [19]	NM	/	4	0.5	/	/	4	/	4	0.3
11	2020 [20]	BMiD EUCAST	/	/	0.06	0.06	/	32	/	/	32
12	2020 [21]	BMiD EUCAST	/	>8	2	4	4	/	/	/	0.125
13	2020 [21]	BMiD EUCAST	/	>8	8	>8	16	/	/	/	0.125
14	2021 [22]	YeastOne	/	2	0.5	2	/	0.5	0.12	0.25	0.5
15	2022 (this study)	BMiD CLSI-M38	64	2	0.5	1	0.06	> 16	4	>16	2

MIC, minimum inhibitory concentration; CLSI: Clinical and Laboratory Standards Institute; EUCAST: European Committee on Antimicrobial Susceptibility Testing; BMiD: broth microdilution; FLC, fluconazole; ITC, itraconazole; VRC, voriconazole; POS, posaconazole; ISA, isavuconazole; CAS, caspofungin; ANF, anidulafungin; MCF, micafungin; AMB, amphotericin B; NM, not mentioned.

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Data availability statement

Data supporting the findings of this study are openly available in online repository at: https://www.ncbi.nlm.nih.gov/sra/PRJNA913408.