LETTER TO THE EDITOR

Refractory lactic acidosis in CD30 positive gastric cancer

Nitipong Permpalung & Nischala Ammannagari &Chrystal D. Price & John A. Fisk & Sara J. Grethlein

Received: 1 January 2014 /Accepted: 6 January 2014# Springer-Verlag Berlin Heidelberg 2014

Lactic acidosis is a very uncommon presentation in non-hematologic malignancies. The underlying pathophysiologyis still unclear.We report an interesting case of refractory lacticacidosis under this condition. A 71-year-old woman with pastmedical history of hypertension and diabetes mellitus type 2presented with mild abdominal pain and exertional dyspneafor 2 weeks. Her vital signs were unremarkable. Physicalexamination was significant for mild conjunctival pallor, scleralicterus, and hepatomegaly without splenomegaly. Initial labo-ratory evaluation revealed hemoglobin 11.3 g/dl, hematocrit32.4 %, WBC 19.5×103 cells/μL (neutrophils 81.2 %, lym-phocyte 9.3 %, no blasts), platelet count 355×103 cells/μL, Na135 mmol/l, K 4.9 mmol/l, Cl 98 mmol/l, CO2 16 mmol/l,BUN 22 mmol/l, creatinine 0.8 mg/dl, pH 7.12 from venousblood gas, Ca 7.4 mg/dl, AST 1,244 U/l, ALT 213 U/l, alkalinephosphatase 584 U/l, total bilirubin 4.8 mg/dl, direct bilirubin3.8 mg/dl, albumin 2.1 g/dl, ammonia 70 μmol/l, INR 1.3,serum lactate 5.4 mmol/l, glucose 117 mg/dl, thiamine202 nmol/l, and negative serum acetone. Viral hepatitis paneland blood cultures were negative. CT scan of abdomenand pelvis demonstrated a heterogeneous lobulated wallthickening of stomach at the greater curvature and in-numerable hepatic masses. Esophagogastroduodenoscopyunveiled a large ulcerated tumor mass filling gastricfundus and body. Endoscopic biopsy results wereinterpreted as being most consistent of CD30-positivepoorly differentiated carcinoma with presumptive liver

metastasis (Fig. 1). Intravenous infusions of isotonicsodium bicarbonate (NaHCO3) solution were adminis-tered. The initial plan was to initiate brentuximab (antiCD30 monoclonal antibody) to decrease the tumor bur-den. Unfortunately, lactic acidosis did not improve de-spite continuous NaHCO3 infusion, and the patient de-veloped fulminant hepatic failure. Eventually, the patientpassed away within a few days of hospitalization.

From a literature review, a few theories have been proposedto explain the pathophysiology of lactic acidosis in this set-ting. Dense clusters of tumor cells with very high turnover ratecould induce anaerobic metabolism and enhance pyru-vate production. In previously reported cases of solidtumor-induced lactic acidosis, the authors found thatalmost 50 % of those cases (Table 1) had extensiveliver metastasis which would decrease pyruvate conver-sion to carbon dioxide and water [1–11]. Our patienthad a combination of these two factors, an aggressivetumor with high turnover rate as well as extensivehepatic metastases impairing pyruvate metabolism,which could have resulted into refractory lactic acidosis.The lactic acidosis failed to respond to sodium bicar-bonate infusions because the primary cause of acidosiswas not yet corrected. Reduction of tumor burden bychemotherapy or radiation has been used in this settingin the previous case reports [2, 3, 6]; however, mostpatients had aggressive cancer with very short survivaltime and were unable to tolerate the treatment. In addi-tion, thiamine deficiency-associated lactic acidosis wasalso proposed in previous reports [4–6].

In conclusion, physicians should be mindful that lac-tic acidosis is not always caused by common causessuch as infection or hemodynamic instability. Solid tu-mors and hematologic malignancies could also result inlactic acidosis.

N. Permpalung (*) :N. Ammannagari : C. D. Price : J. A. Fisk :S. J. GrethleinCollege of Physicians and Surgeons, Bassett Medical Center andColumbia University, One Atwell Road, Cooperstown, NY 13326,USAe-mail: nitipong.permpalung@bassett.org

Ann HematolDOI 10.1007/s00277-014-2011-6

Acknowledgments The authors would like to thank Dr. Robert E.Hutchison at SUNY Upstate Medical University who provided the out-side hematopathology consultation.

Conflict of interest The authors declare that they have no conflict ofinterest.

Funding source None.

References

1. O’Neill G, TormeyWP, FarrellMA et al (1993) Phaeochromocytomaand lethal lactic acidaemia. Ir Med J 86:211

2. Evans TR, Stein RC, Ford HT et al (1992) Lactic acidosis. Apresentation of metastatic breast cancer arising in pregnancy.Cancer 69:453–456

3. Warner E (1992) Type B, lactic acidosis and metastatic breast cancer.Breast Cancer Res Treat 24:75–79

4. Kuba H, Inamura T, Ikezaki K et al (1998) Thiamine-deficient lacticacidosis with brain tumor treatment. Report of three cases. JNeurosurg 89:1025–1028

5. de Groot R, Sprenger RA, Imholz AL et al (2011) Type B lacticacidosis in solid malignancies. Neth J Med 69:120–123

6. Espinoza AM, Venook AP (2011) Lactic acidosis and colon cancer:oncologic emergency? Clin Colorectal Cancer 10:194–197

7. Fujimura M, Shirasaki H, Kasahara K et al (1998) Small cell lungcancer accompanied by lactic acidosis and syndrome of inappropriatesecretion of antidiuretic hormone. Lung Cancer 22:251–254

8. Manuel B, Suresh V, Saphwat E (2006) Refractory metabolic acido-sis in small cell cancer of the lung. South Med J 99:782–783

9. Munoz J, Mohd K, Amr H et al (2011) Severe lactic acidosis in apatient with metastatic prostate cancer. J Cancer Res Ther 7:201–202

10. Muntz HG, Brown E (1992) Lactic acidosis and hypoglycemia: ametabolic complication of advanced gynecologic malignancy. Int JGynecol Cancer 2:163–167

11. Blüher S, Schulz M, Bierbach U et al (2008) Central lactic acidosis,hyperventilation, and respiratory alkalosis: leading clinical features ina 3-year-old boy with malignant meningeal melanoma. Eur J Pediatr167:483–485

Fig. 1 aEndoscopic biopsy of the stomach mass consisted of numerousfragments of gastric mucosa and underlying tissue largely replaced by aninvasive anaplastic tumor composed of solid sheets of large, markedlyatypical cell with regions of coagulative type tumor necrosis and fibrosis.Tumor cells had large, oval to focally indented nuclei, coarsely granular

chromatin, prominent central nucleoli, and moderate amounts ofamphophilic, foamy cytoplasm. Numerous apoptotic bodies and mitoticfigures were noted including abnormal forms. b The immunoperoxidasestaining of formalin-fixed, paraffin-embedded sections showed strongand diffuse staining of the tumor cells against CD30

Table 1 Lactic acidosis in non-hematologic malignancies in 1990–2013

Organ Cell type Age Sex Livermetastasis

Other distantmetastasis

Contributing factors Reportedyear

Adrenal medulla [1] Pheochromocytoma 59 F − − Increased adrenaline 1993

Breast [2] Adenocarcinoma 36 F + − N/A 1991

Breast [3] Adenocarcinoma 67 F + Bone, LN Previous CTX 1992

Breast [4] Adenocarcinoma 41 F − Brain Previous CTX, thiamine deficiency 1998

Breast [5] Infiltrating ductal carcinoma 86 F + − Thiamine deficiency 2011

Colon [6] Adenocarcinoma 44 F + Lung Thiamine deficiency 2011

Lung [7] Small cell lung cancer 70 M − Bone N/A 1998

Lung [8] Small cell lung cancer 64 M + − N/A 2006

Prostate gland [9] Adenocarcinoma 71 M + Bone Previous CTX 2011

Uterus [10] Endometrial carcinoma 72 F − Intestine, ovaries, cervix Hypoglycemia 1992

Miscellaneous [11] Meningeal melanoma(central lactic acidosis)

3 M − − N/A 2007

Mmale, F female, LN lymph node, CTX chemotherapy

Ann Hematol