Clinicopathological Conference

CPC # 1550 AUTOPSY (NTUH A 10706)

Dr. Richard Cabot, 1868 - 1939

RESTRICTION: BRAIN part of liver, lungs, kidney, spleen, sternum, skin and heart
Performed on 2022/02/29 (2 day after death)
R3 陳漢和 /R4王堉睿 /VS吳木榮
Patient Profile: 69-year-old, female
Past History:
Left breast cancer, s/p resection in 1998 (45 y/o), s/p adjuvant chemotherapy
Present illness:
Initial presentation: bilateral lower limbs petechiae for one year (2021/2)
Diagnosis: Myelodysplastic neoplasm with excess blasts-2 (台北慈濟, 2021/2)
Blasts make up 10% to 19% of the cells in the bone marrow, or 5% to 19% of the cells in the blood
Acute myeloid leukemia, myelodysplasia-related
NTUH: Leptomeningeal and cauda equina involvement (paraplegia + urinary
incontinence + facial palsy) – s/p triple intrathecal therapy (TIT) (2022/3-4);
s/p craniospinal irradiation (2022/4-5); Complete remission (2022/5)
s/p conditioning chemotherapy, fludarabine(Flu) + busulfan(Bu) +
cyclophosphamide(Cy); s/p hematopoietic stem cell transplant (donor: her son,
BM&PB) (2022/6/20)
Fever (2022/6/22) -> B/C: ESBL E.coli; s/p Abx
Fever (2022/7/8) with diarrhea (r/o GI GVHD) s/p Abx, steroid -> diarrhea improved
fever and diarrhea on and of ….
Hospital-acquired pneumonia (2022/7/29) with shock + acute respiratory failure
CT: RUL, RLL and LLL peri-bronchial consolidation
Hospital-acquired pneumonia (2022/7/29) with shock + acute respiratory failure
s/p intubation, VV-ECMO, CVVHDF, antibiotics, steroid, inotropes
VV-ECMO removed on 2022/8/5 ☆ No cultural evidence
 Neutropenic fever (2022/8/12) with Profound spetic shock with susp. invasive fungal
infection (Aspergillus Ag+ on 8/15) Possible invasive fungal infection
s/p voriconazole (2022/05/31-07/29); amphotericin B (2022/07/29-08/09);
isavuconazole (2022/07/29-8/02); voriconazole (2022/08/16-08/19) for Aspergillus
Ag+ (8/15) isavuconazole (2022/08/19-08/29)
CMV prophylaxis: s/p letermovir (2022/06/21-07/31) (2022/08/16-08/24)

ARDS and suspected GVHD; s/p VV-ECMO, CVVH, G-CSF, IVIG, abx, steroid,
inotropes; DIC (PLT↓ + fibrinogen↓); worsened liver function (T-bil↑, ammonia↑,
INR↑); progressive lactic acidosis -> passed away due to multiorgan failure on
2022/8/27

STATUS POST CRAVIT / AMIKACIN / STATUS POST CRAVIT / AMIKACIN /

ISONIAZID / INH / EMB (2022/08/9-08/22)
ISONIAZID / INH / EMB (2022/08/9-08/22
BL: 149.6 cm; BW: 65.5 kg
Skin of right side of chest
 Skin of left lower abdomen

Vacuolar change, dyskeratosis, subepidermal clefting, ulceration

c/w aGVHD, grade III; Other stains: HSV(-), CMV(-)
 Skin of left lower abdomen

Vacuolar change, dyskeratosis, subepidermal clefting, ulceration

c/w acute GVHD, grade III; Other stains: HSV(-), CMV(-)
small amount of serosanguineous pleural effusion
Sternum
~15%
Hypocellular marrow,
with marked decrease
of myeloid, erythroid
and megakaryocytic
series, reactive
histiocytosis and
deposition of
hemosiderosis
Heart: 402 grams (Ref: 200-280 grams)
Right ventricle: 0.6 cm Left ventricle: 1.5 cm
RV LV
HSP70 (+, F)
Right Lung: 713 grams
(Ref: 360-570 grams)
Right lung
Left Lung: 468 grams (Ref: 325-480 grams)
Left upper lung
What kinds of
pneumonia?
RUL LUL

RML

LLL

RLL
LUL
LUL reactive type II pneumocyte hyperplasia
LUL: pulmonary vein thrombosis
RML Masson's trichrome
Histiocytic type, non-granulomatous or necrotizing
inflammation, with fibrinofibrous pneumonitis and
interstitial fibrosis
Full Workup Pathogen stains of lungs:
PAS(-); GMS(-); CMV(-), HSV(-), BKV(-), SV40(-), HHV8(-), AFS(-)
AFS stain (-)
Liver: 1487 grams (Ref: 1500-1800 grams)
Centrilobular submassive necrosis,
Esp. zone 3
Centrilobular submassive necrosis, Esp. zone 3
PAS stain (loss)
Oil red stain (+)
CD68(+)
AFS (+)
Masson‘s trichrome stain Reticulin
Iron stain
Iron stain
glutamine synthetase (-) GLUT-1: zone 3; hypoxic/ischemic

Other stains for liver: CMV(-), PAS(-), Fontana-Masson(-)

Spleen: 90 grams
CD45: lymphoid depletion
CD45: lymphoid depletion
Iron stain
Left kidney: 158 grams (Ref: 120-175 grams)

Bile acid nephropathy

Diffuse acute tubular necrosis c/w shock-related
 Iron

Bile acid nephropathy

Nephrosclerosis
 Postmortem Culture Results
Lung biopsy (2022/08/29): Chryseobacterium indologenes enriched (CLABSI-related) ;
Enterococcus faecium enriched ;
No anaerobic pathogen; AFS+Culture: No growth after 8 weeks
AF Stain: Acid fast bacilli – Negative
No Fungus

Bronchoscope specimen (2022/08/29): PCR for M.tuberculosis complex: Detected

Bronchial wash (2022/08/29): CMV viral load (IU/mL): <34.5
Blood (2022/08/29): EBV Viral Load(IU/mL): 690

Liver biopsy (2022/08/29): Chryseobacterium indologenes enriched (CLABSI-related) ;

No anaerobic pathogen; AFS+Culture: No growth after 8 weeks;
AF Stain: Acid fast bacilli - positive 1+;
No Fungus
Nasopharyngeal Swab (2022/08/29): All negative
Parainfluenza type3; SARS-CoV-2; Influenza A/H1; Influenza A/H1-2009
Bordetella pertussis; Human metapneumovirus; Influenza A/H3; Coronavirus NL63
Parainfluenza type2; Mycoplasma pneumoniae; Coronavirus HKU1; Coronavirus OC43
Parainfluenza type1; Chlamydophila pneumoniae; Human Rhinovirus/Enterovirus
Coronavirus 229E; Influenza A; Parainfluenza type4; Adenovirus
Influenza B; Respiratory Syncytial Virus; Bordetella parapertussis; SARS-CoV-2
Issues to be Clarified
● Complete remission of myelodysplasia-related
acute myeloid leukemia?
Yes (2022/5), negative leukemic or myelodysplastic
blast cells
Issues to be Clarified
 Nature of peri-bronchial pneumonia of lung?

Full Workup Pathogen stains of lungs:

PAS(-); GMS(-)CMV(-), HSV(-), BKV(-), SV40(-), HHV8(-), AFS(-)
Chryseobacterium indologenes (CLABSI-related)

(craniospinal irradiation)
 (craniospinal irradiation)

Microbiol Spectr. 2016 Nov;4(6)

Issues to be Clarified
 Nature of Acute Hepatic Failure?
Issues to be Clarified
 Nature of Acute Hepatic Failure?
 WBC AST ALT

T-Bil INR
CRP

D-dimer
ALP

Lactic acid
Ammonia
Fibrinogen
Issues to be Clarified
 Nature of Acute Hepatic Failure?
Ethionamide 藥物作用機轉
 Issues to be Clarified
 Role of post HSCT
iron overload

Bone Marrow Transplant 26, 649–655 (2000)

 MRI (2022/5/20) before transplant:
Decreased signal on T2WI in the liver and spleen,
suggestive of iron overload

Autopsy:
Hemosiderosis in liver, spleen and bone marrow HSCT in 2022/6
Adv Hematol. 2010;2010:345756.
 Iron overload
- Liver dysfunction
- A common chronic complication occurring
in 50%–72% of patients
Adv Hematol. 2010;2010:345756.
Aliment Pharmacol Ther. 2006 Aug 1;24(3):441-52.
Sinusoidal obstruction syndrome

PathologyOutlines
bridging congestion Biopsy Interpretation of the Liver
 Acute GVHD (X)

Biopsy Interpretation of the Liver

Aliment Pharmacol Ther. 2006 Aug 1;24(3):441-52.
Aliment Pharmacol Ther. 2006 Aug 1;24(3):441-52.
Conclusion

The cause of liver function deterioration:

Drug (Ethionamide, Cravit, Voriconazole)
Shock (Septic shock, centrilobular ischemic necrosis)
Hemosiderosis -> less likely
Tuberculosis in hematopoietic stem cell transplant recipients
Bone Marrow Transplant. 2000 Aug;26(3):291-8.
Issues to be Clarified
● Acute GVHD? Yes, Grade III, ? GI tract
Issues to be Clarified
● Disseminated Intravascular Coagulopathy (DIC)

Yes,
Take Home Massages

Complete remission of acute myeloid leukemia

Disseminated mycobacterial infection, histiocytic type,

non-granulomatous infection, lungs and liver

Acute and fatal anti-tuberculous drug-induced liver injury,

submassive necrosis of liver with iron-overload and bile
acid nephropathy

Acute Graft-versus-host-disease, Grade III, skin

Disseminated Intravascular Coagulopathy (DIC)