Type B Lactic Acidosis in a Solid Tumor Malignancy
without Liver Metastases: A Rare Case of Refractory
Beatrice Preti
, MD, Jasna Deluce
, MD, Siddhartha Srivastava
, MD, MSc
Division of General Internal Medicine, Department of Medicine, Queens University, Kingston, Ontario, Canada
Kingston Health Sciences Center, Kingston, Ontario, Canada
Author for correspondence:
13 February 2020; Accepted after revision: 27 April 2020; Published: 21 June 2021
Malignancy-induced type B lactic acidosis is a rare, yet fascinating, cause of refractory acidosis
in patients with cancer, often unresponsive to usual medical treatments. Case reports usually
discuss the paraneoplastic phenomenon in hematologic malignancies; however, we present the
case of a 72-year-old woman with metastatic breast cancer, who initially presented to hospital
with an elevated lactate in the absence of acidosis. She appeared to improve with fluids; however,
she then represented 2 weeks later with a severe metabolic acidosis and undetectable high lactate
level. Ultimately, the patient did not respond well to supportive care, and the decision was made
to pursue comfort-directed therapy.
Lacidose lactique de typeB induite par une tumeur est une cause rare, mais extrêmement
intéressante, dacidose réfractaire chez les patients cancéreux et qui, souvent, ne répond pas
aux traitements médicaux habituels. Les études de cas traitent généralement du phénomène
paranéoplasique des tumeurs malignes hématologiques; toutefois, nous présentons le cas dune
femme de 72ans atteinte dun cancer du sein métastatique, qui sest dabord présentée à l’hôpital
pour un taux élevé de lactate dans le sang, mais sans acidose. Son état a semblé saméliorer grâce
à un apport de liquides; toutefois, elle sest présentée de nouveau à l’hôpital deux semaines plus
tard pour une acidose métabolique grave et un taux élevé de lactate indétectable. Au bout du
compte, la patiente na pas bien répondu aux soins de soutien, et il a été décidé dappliquer les
soins de confort.
Case Presentation
A 72-year-old woman was admitted to hospital with a 2-day
history of weakness, malaise, nausea, and decreased oral intake,
as well as a 1-day history of expressive aphasia and word-finding
difficulties. She had a similar recent presentation to hospital 2
weeks prior, during which she was diagnosed with hypercalcemia
and treated with intravenous pamidronate. The patient also
reported 2 months of gradual functional decline and a 20-pound
unintentional weight loss. On review of systems, she had no
infectious symptoms, including cough, shortness of breath, fever
or chills, abdominal pain, diarrhea, lower urinary symptoms,
mouth sores, or other neurological symptoms.
Her past medical history was significant for metastatic,
triple-negative, invasive ductal carcinoma of the left breast,
T3N1, status post-mastectomy, and adjuvant radiation, with
metastases to the left chest wall and pancreatic tail found
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Case Reports and Clinical Images
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during her previous hospital admission. Her most recent CA
15-3-K was 512 kU/L (normal 0–31); CEA was 3.3 ug/L (normal
0–5). She also had a previous history of triple-positive breast
cancer in the left breast, depression, and severe compression
fractures of the lumbar spine. Her home medications consisted
of long-acting morphine for pain and trazodone for insomnia.
During her prior hospital admission, she was hemodynamically
stable, but had been found to have an elevated anion gap with
a compensated metabolic acidosis on a venous blood gas (pH
7.35, pCO
32mmHg, HCO
18mmol/L). She had elevated
beta-hydroxybutyrate at 1.14mmol/L, thought to be related to
malnutrition ketosis in the setting of her cancer. Her lactate
was also significantly elevated (15.3mmol/L), which improved
moderately with intravenous fluids to 11.6mmol/L.
Upon representation to hospital, the patient was tachycardic,
with a heart rate of 105 beats per minute, blood pressure of 127/73,
respiratory rate of 16, oxygen saturation of 96% on room air,
and temperature of 36.6° Celsius. She appeared comfortable and
was sitting up reading. She was mildly cachectic, and physical
exam was consistent with hypovolemia: dry axilla, dry mucus
membranes, and flat jugular venous pressure. Otherwise, her
cardiac, respiratory, and abdominal exams were noncontributory.
Neurologically, she was alert and oriented but had noticeable
word finding difficulties and self-reported confusion; however,
the remainder of her neurological exam was normal. She had a
small, stage two sacral ulcer with no discharge or surrounding
The full panel of her laboratory investigations is listed in Table 1.
Notably, laboratory results again demonstrated hypercalcemia and
a high anion gap metabolic acidosis with significantly elevated
lactate (>17 mmol/L). A chest X-ray showed new compression
fractures. A bone scan showed no clear metastasis. A CT of the
chest, abdomen, and pelvis showed no liver lesions but did show
new metastasis in left chest wall and pancreatic tail.
Her hypercalcemia was treated with 2 L of intravenous (IV)
normal saline bolus and IV zoledronic acid. Her constipation,
confusion, and word-finding difficulties resolved by the following
morning, leaving only mild residual nausea. She was started
on a bicarbonate infusion in an attempt to treat the persistent
acidosis. Despite continuing the bicarbonate infusion for several
days, however, the patients lactate remained undetectably high,
and the blood pH remained acidotic. She still appeared clinically
well, and was thus transitioned to oral bicarbonate.
A number of causes for lactic acidosis, including thiamine
deficiency, sepsis, renal dysfunction, hepatic dysfunction, and
hypoxia, were ruled out (Table 1). She had no history of toxic
alcohol ingestions or any pharmaceutical culprits. Ultimately, it
was determined her lactic acidosis was malignancy-induced. She
was treated for type B lactic acidosis associated with malignancy
supportively, and treatment for the underlying malignancy was
considered. Hence, medical oncology was consulted, and she
was offered palliative systemic chemotherapy. However, the
patient and her family decided to focus on symptom-directed
care only. She died in hospital 2 weeks later.
Lactic acidosis is defined as a serum pH less than 7.35 coupled
with a serum lactate greater than 5 mmol/L.
There are three
types of lactic acidosis described in the literature: Type A,
Type B, and Type D.
Type A represents lactate overproduction
secondary to hypoperfusion and tissue hypoxia. Type D lactic
acidosis is an uncommon subtype, occurring mainly in the setting
of gastrointestinal malabsorption and short bowel syndrome.
This case presentation shows an example of Type B lactic
acidosis, defined as nonhypoxia-induced lactic acidosis. Causes
of Type B lactic acidosis include medications (such as metformin
and propofol), alcohol intoxication, and, rarely, malignancy.
Malignancy-induced Type B lactic acidosis was first described
in 1963, observed in a patient with leukemia.
Since then, there
have been case reports of lactic acidosis in patients with both
hematologic and, less commonly, solid tumor malignancies. In
the realm of solid tumors, metastatic small cell carcinoma and
undifferentiated carcinoma represent the leading causes identified
in the literature.
We performed a literature search in MEDLINE
and PUBMED with search strategy of terms “lactic acidosis,
solid tumors,and MeSH terms for neoplasmsand acidosis,
lactic, respectively, from 1970 to 2018. Most cases of solid-tumor
Type B lactic acidosis in the literature (90% +) are associated
with liver metastases; indeed, there are only an isolated number
reported in the literature in recent years (Table 2). A 1992 review
article of malignancy-induced Type B lactic acidosis reported
three cases of solid-tumor-induced lactic acidosis without liver
metastases, one of which was a sarcoma, which rarely spreads to
the liver.
A 2011 literature review subsequently found no cases
of solid-tumor-induced lactic acidosis without liver metastases
in a 10-year period.
We report a case of a rare cause of lactic
acidosis arising in a breast cancer without known liver metastases;
a similar case does not appear to be reported in the literature.
The mechanism by which malignancy leads to Type B lactic
acidosis is not fully understood. However, popular speculation
suggests a form of aerobic glycolysis, termed the “Warburg
As tumors expand, cancer cells frequently outgrow their
original blood supply. Survival of the fittest preferentially selects
those cells with maximal capacity for anaerobic (lactic-acid-
producing) glycolysis. However, via the Warburg Effect, some
of these same cancer cells have developed the ability to engage
in anaerobic glycolysis even in the presence of oxygen (hence,
aerobic glycolysis”).
This leads to an overproduction of lactic
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Preti B et al.
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Table 1. Laboratory Values
Lab variable Normal reference range
blood work
Prior admission
day 10 blood
blood work
admission day 3
blood work
White cell count 4.0–10.5 × 10
/L 9.1 5.7 6.0 4.2
Hemoglobin 3.7–5.1 × 10
/L 104 95 87 69
Platelets 150–400 × 10
/L 102 60 59 43
Calcium 2.25–2.80 mmol/L 3.09 2.62 2.82
Ionized calcium 1.15–1.32 mmol/L 1.45 1.41
Phosphate 0.74–1.52 mmol/L 1.07 1.26
Magnesium 0.66–1.07 mmol/L 0.86 0.91
Sodium 133–145 mmol/L 138 140 138
Potassium 3.7–5.5 mmol/L 4.5 4.3 4.4
Chloride 97–110 mmol/L 97 94 101
Urea 4–8 mmol/L 10.4
Glucose, random 3.5–11.1 mmol/L 4.8
Total CO
19–27 mmol/L 17 22 8
Anion Gap 8–12 24 24 29
Creatinine 0–85 umol/L 69 50
LDH 120–315 U/L 472
Uric acid 155–365 umol/L 349
Albumin 35–38 g/L 35 35
AST 10–35 U/L 32 76 28
ALT 8–40 U/L 17 46 22
ALP 61–157 U/L 126 132 328
GGT 3–45 U/L 34
Bilirubin (total) 0–17 umol/L 9 14 10
INR 0.9–1.1 1.4
Lipase 0–79 U/L 23
BOHB 0.00–0.37 mmol/L 1.12 1.14
Lactate 0.5–2.2 mmol/L 15.3 >17 >17
VBG (pH) 7.32–7.43 7.35 7.08 7.22
) 40–50 32 27 27
VBG (pO2) 37 18 15
VBG (HCO3) 22–29 18 8 11
PTHrP 14–27 pg/mL 11
PTH 2.0–9.4 pmol/L 1
Thiamine 75–225 nmol/L 162
Serum osmolality 281–297 mmol/kg 309
Acetaminophen 54–112 umol/L <20
Blood cultures No growth
TSH 0.40–4.50 mIU/L 1.16
B12 140–650 pmol/L 196
Reticulocytes 30–120 × 10
/L 72
Ferritin 4–205 ug/L 356
Folate 7–45 nmol/L 26
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Type B lactic acidosis
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acid, which may ultimately lead to lactic acidosis. It has been
hypothesized that the ability to engage in aerobic glycolysis lends
cancer cells an advantage in cell proliferation.
Specifically, the
acidic environment created by lactate around cells may contribute
to genomic instability, local invasion, progression to metastatic
disease, and resistance to treatment.
This process is more likely
to occur in the setting of liver metastases (and consequent
functional impairment) as roughly 80% of the body’s lactate is
metabolized in the liver.
Of course, not all malignancies lead to lactic acidosis. Risk
factors identified in the literature include nutritional deficiencies
(such as thiamine deficiency), hepatic or renal impairment (e.g.,
from liver metastases or chronic conditions), and a high rate
of tumor cell proliferation.
Clinical examination is typically
nonspecific but may include Kussmaul respirations (tachypnoea
without hypoxia) and refractory hypoglycemia despite intravenous
dextrose administration.
Treatment of malignancy-induced Type B lactic acidosis
is mainly supportive and the diagnosis itself conveys a poor
Most patients diagnosed with malignancy-related
lactic acidosis will die within hours to months.
The best-
known treatment is chemotherapy or systemic treatment of the
underlying malignancy.
Supportive treatment with thiamine
supplementation has been shown to have no risk in the acute
setting, albeit the degree of potential benefit being unclear. Renal
and bicarbonate drips
have not been shown to
have any improvement or change in outcome.
Solid tumor malignancies without liver metastases represent a
rare cause of Type B lactic acidosis. However, malignancy is an
important cause of lactic acidosis and should be considered in
patients presenting with elevated serum lactate in the setting
of acidosis without clear hypoperfusion and tissue hypoxia,
particularly when routine measures such as antibiotics and
intravenous bicarbonate infusions do not induce improvement.
Table 2. Reported Cases of Solid-Tumor-Induced Lactic Acidosis without
Liver Metastases
Case Year Tumor
Nair R, Shah U 2017 Lung primary
Rao KS, Mehta R, Ferlinz J 1988
Lung primary, Squamous cell
Stacpoole PW, Lichtenstein
ML Polk JR et al.
1981 Sarcoma
Fraley DS, Adler S, Bruns FJ,
Zett B
1980 Lung primary
Finally, malignancy-associated lactic acidosis suggests a poor
overall prognosis.
Key Points
1. The causes for lactic acidosis expand beyond the typical
culprits for shock.
2. Risk factors for malignancy-associated lactic acidosis
include nutritional deficiencies, hepatic impairment,
renal impairment, and a high rate of cell proliferation.
3. Treatment for malignancy-associated lactic acidosis is
focused on treating the underlying malignancy.
4. Malignancy-associated lactic acidosis suggests a poor
overall prognosis.
Competing Interests
This article has been peer reviewed.
The authors have obtained written patient consent.
All authors have contributed substantially and equally to the
data acquisition, interpretation, concept, and design of the
manuscript. Beatrice Preti reviewed the literature and drafted
the initial manuscript. Jasna Deluce and Siddhartha Srivastava
were involved with the case, described the case, and reviewed
and revised the manuscript. All authors gave final approval for
the version to be published and agreed to act as guarantors of
the work.
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Type B lactic acidosis
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