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Clinical  Management  Issues   2011; 5(Suppl 2) 75

Clinical Management Issues

Case report

A 70-year-old teacher, a good eater, didn’t 
drink any wine and any alcoholic drinks. His 
intestinal transit and his diuresis were nor-
mal. He was a nonsmoker, a single and he 
didn’t take any therapy.

In his past medical history we found hy-
pertension, prostatic hypertrophy, appen-
dectomy, and melanoma in the left arm in 
2002. In November 2008 he was admitted 
to Hospital because of wheezing with fever 
chills, symmetrical arthralgias, and relevant 
asthenia. He was apiretic. Physical examina-
tion revealed obtuseness chest and showed 
mean pleural effusion; the neurological 
examination showed that the patient was 
sound; the cranial nerve function was ob-
served: the sensation, the muscle strength, 
and tenden reflex were normal.

The heart sound was normal, and there 
were no oedema on lower extremities. In the 
abdomen we found no specific abnormalities 
and Blumberg sign was negative. There were 

IntroduCtIon

Pure red cell aplasia (PRCA) describes 
a condition where the RBC precursors in 
bone marrow are nearly absent, while meg-
akaryocytes and WBC precursors are usu-
ally present at normal levels. In 1922, this 
condition was recognised by Kaznelson [1] 
as a different entity from aplastic anaemia. 
Pure red cell aplasia exists in several forms, 
and the most common one is an acute self-
limited condition. 

Acquired pure red cell aplasia is chronic 
and is often associated with underlying 
disorders like thymomas [2], lymphomas 
[3], and autoimmune diseases. Initially a 
congenital form of pure red cell aplasia 
was described by Joseph in 1936 and by 
Diamond-Blackfan in 1938 [4]. Congenital 
pure red cell aplasia is a lifelong disorder, 
and it is associated with physical abnormali-
ties. Both acquired and congenital pure red 
cell aplasia are occasionally refractory to 
therapy (Table I).

Corresponding author
Dott. Massimo Incagliato
incagliatom@virgilio.it

Caso clinico

abstract
We report a case of acquired pure red cell aplasia (APRCA) associated with carcinoma of the 
tongue: the first was considered a rare paraneoplastic syndrome. We point out that there is no 
case in literature with this association.
After surgical operation (subglottic laryngectomy + right lymphadenectomy + laterocervical 
on the right) the transfusions required, at the beginning very frequent, decreased relevantly. 
This is a typical case where the paraneoplastic syndrome precedes the diagnosis of the primary 
carcinoma of the tongue (one year before what happens in bronchogenic carcinoma).

Keywords: pure red cell aplasia, paraneoplastic syndrome, carcinoma of the tongue
Un raro caso di aplasia eritroide pura che occulta un carcinoma squamoso della lingua
CMI 2011; 5(Suppl 2): 75-79

1 Division of Internal 
Medicine, Hospital San 
Giacomo, ASLAL Novi 
Ligure (AL)

2 Division of Haematology, 
Hospital San Biagio, 
Alessandria

3 Department of Clinical 
and Laboratory 
investigation, Hospital San 
Martino, Genova

Massimo Incagliato 1, Antonella Daffonchio 1, Lidia Celesti 1, Amedeo Bottero 1, Francesco Balbi 1, Massimo 
D’Ulizia 1, Emilia Ballestrero 1, Monia Costanzo 1, Valeria Primon 2, Amelia Leone 3, Giancarlo Gambarotta 1

an unusual case of secondary 
pure red cell aplasia (prCa)  

that occults a squamous 
carcinoma of the tongue



©SEEd Tutti i diritti riservati
Clinical  Management  Issues   2011; 5(Suppl 2)76

An unusual case of secondary pure red cell aplasia (PRCA) that occults a squamous carcinoma of the tongue

= 3.9 g/dl) [6]. For this test, in accordance 
with the criteria proposed by Light, this 
pleural effusion was considered an exudate 
[6]. Culture of infected pleural fluid yielded 
negative results.

The echocardiography presented minimal 
pericardial effusion.

The haematic tests revealed lymphocytes = 
55% and neutrophils = 42%. Cytology find-
ings were negative for neoplastic cells. 

Because of the negativity of the clinical 
examinations during hospitalisation, the pa-
tient was transferred to the Thoracic Surgery, 
where he was subjected to pleural biopsy: 
the pathologic specimen showed a chronic 
pleuritis. During hospitalisation ticarcil-
lin 4.5 mg × 3, prednisone 50 mg/die, and 
a gastroprotective drug were administered. 
The patient was discharged after 20 days 
with good resolution of the general clinical 
condition and an outpatient follow-up was 
arranged. At home the patient continued 
steroid treatment since there was the sus-
pect of a possible form of autoimmune dis-
ease (maybe systemic lupus erythematosus). 
This suspicion roused by the results of the 
following tests: positive antibody and native 
DNA, pleural effusion, and pericardial effu-
sion associated with moderate megaloblastic 
anaemia, which was already present since 
some time.

In March 2009 he was re-hospitalised in 
Department of Internal Medicine for se-
vere megaloblastic anaemia (Hb = 5.8 g/dl; 

no skin lesions, the genitals were normal, and 
we found no rash and no lymphadenopathy. 
He was overweight.

The blood tests revealed the results shown 
in Table II.

Tuberculin skin testing (Mantoux test) 
and a single smear-sputum sample for My-
cobatterium tuberculosis were negative. The 
urinalysis and proteinuria were normal. The 
testing stool for the presence of haemoglobin 
was negative. The electrocardiogram (ECG) 
showed a normal rhythm at a rate of 87 bpm. 
The cystoscopy explored prostate lobes, find-
ing mucosal hyperaemia bleeding heavily at 
the passage of the instrument. The bladder 
mucosa was regular.

The neck/thoracic Magnetic Resonance 
Imaging (MRI) detected a pleural effusion 
on the left. The MRI performed on the ab-
domen showed gallbladder-renal calculi and 
prostatic hypertrophy. The chest CT con-
firmed the gallbladder calculi and the abun-
dant pleural effusion on the left, adding the 
detection of not dependent focal lesions of 
the remaining lung parenchyma. The tracheal 
and bronchial branches were normal, such as 
adrenal glands. The PET was negative.

A thoracentesis was performed for pleural 
effusions: the ratio of pleural fluid to serum 
protein resulted greater than 0.5. The ratio 
of pleural fluid to serum lactate dehydroge-
nase (LDH) was greater than 0.6. Pleural 
fluid LDH is greater than two thirds of the 
upper limits of normal serum value (protein 

“Congenital” form (diamond-Blackfan anaemia)
acquired prCa
Parvovirus B19 infection

Transient aplastic crisis (TAC) in patients with shortened erythrocyte life span  y
Chronic type of bone marrow failure in immunosuppressed patients y

Immunological suppression of erythropoiesis
Antibody mediated y

Antibody against red-cell progenitors •
Transient erythroblastopenia in childhood (TEC) ·
Adult form ·
AB0-incompatibility following bone marrow transplantation ·

Antibody against erythropoietin •
αβ or γδ T cell-mediated

T-helper cell-mediated antibody production y
MHC-restricted, recognition of red-cell progenitors y
MHC-unrestricted recognition of red-cell progenitors y

NK cell- or T cell-mediated
MHC-unrestricted cytotoxicity  y

associated with pregnancy
associated with certain drugs and toxins
Initial manifestation of a pre-leukaemic syndrome

table I
Types of pure red cell 
aplasia. Modified from 
[5]



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Clinical  Management  Issues   2011; 5(Suppl 2) 77

M. Incagliato, A. Daffonchio, L. Celesti, A. Bottero, F. Balbi, M. D’Ulizia et al

The biopsy of the bone marrow revealed 
a 20% cellularity (hypocellular) and a nor-
mal myeloid series. The erythroid series 
was aplastic, while the megakaryocytic one 
resulted hyperplastic. We found also inter-
stitial infiltrates of lymphocytes for 25% of 
elements with immunophenotype CD3-
CD20 positive (reactive lymphocytes), 
and CD34 cells 2%. The test for the PNH 
(Paroxysmal Nocturnal Haemoglobinuria) 

platelets = 150,000/mm3; MCV = 110 fl), 
dyspnoea, and tachycardia.

The gastroscopy performed showed 
chronic gastritis, while the colonscopy was 
normal.

A computed tomographic scanned neck, 
chest, abdomen with administration of con-
trast material: the main pulmonary artery 
and the pulmonary arterial vasculature were 
normal, such as the lung parenchymal.

parameter results normal range

WBC 4,990/mm3 4,500-11,000/mm3

Neutrophils 40% -
Lymphocytes 55% -
Plts 150,000/mm3 150,000-350,000/mm3

Hb 10.5 g/dl 14-18 g/dl
MCV 110 fl 80-100 fl
ESR 31 mm/hour 2-10 mm/hour
INR 1.1 0.8-1.2
Fibrinogen 278 mg/dl 175-400 mg/dl
Glucose 97 mg/dl 70-110 mg/dl
Urea 37 mg/dl 10-50 mg/dl
Creatinine 1 mg/dl 0-1.5 mg/dl
Total cholesterol 112 mg/dl < 200 mg/dl
TAG 142 mg/dl 40-170 mg/dl
Total bilirubin 0.8 mg/dl < 1 mg/dl
Uric acid 5.7 mg/dl 3.6-8.5 mg/dl
Ferritin 226 ng/dl 30-300 ng/dl
Na+ 146 mEq/l 135-145 mEq/l
K+ 4.4 mEq/l 3.4-4.8 mEq/l
GOT 25 U/l 9-25 U/l
GPT 24 U/l 7-30 U/l
GGT 37 U/l 7-33 U/l
ALP 50 U/l 40-115 U/l
LDH 493 U/l 110-210 U/l
PT 5.8 sec 11-16 sec
Amylase 42 U/l 10-220 U/l
Lipase 30 U/l 114-286 U/l
Alpha fetoprotein 1.38 ng/ml < 10 ng/ml
CEA 1.6 ng/ml < 5 ng/ml
Ca 19-9 30 U/ml 0-40 U/ml
CRP 0.3 mg/l < 8 mg/l
ACE 7 nmol/ml 8-22 nmol/ml
Vitamin B12 675 µg/dl 200-900 µg/dl
Folic acid 13 ng/ml 3.1-17.5 ng/ml
HIV Negative -
HBV Negative -
HCV Negative -
ANA 1:640 -
ENA Negative -
LAC Negative -
ACA Negative -
B2GP1 Negative -
Anti-dsDNA Positive  -
C3 In range
C4 In range
Rheumatoid factor In range
Antibodies CCP In range

table II
Results of the blood tests 
performed
ACA = Anti-Cardiolipin 
Antibody;  
ACE = Angiotensin 
Converting Enzyme;  
ALP = ALkaline 
Phosphatase;  
ANA = ANtinuclear 
Antibody;  
Antibodies CCP = 
antibodies anti-citrulline;  
B2GP1 = Beta 2 
GlycoProtein 1 Antibody;  
C3 = C3 complement 
component;  
C4 = C4 complement 
component;  
Ca 19-9 = Carbohydrate 
antigen 19-9;  
CEA = CarcinoEmbryonic 
Antigen;  
CRP = C Reactive Protein;  
dsDNA = double-stranded 
DNA;  
ENA = anti-Extractable 
Nuclear Antigens;  
ESR = Erythrocyte 
Sedimentation Rate;  
GGT = Gamma-Glutamyl 
Transferase;  
GOT = Glutamic 
Oxaloacetic Transaminase;  
GPT = Glutamic Pyruvic 
Transaminase;  
HBV = Hepatitis B Virus;  
HCV = Hepatitis C Virus;  
HIV = Human 
Immunodeficiency Virus;  
INR = International 
Normalized Ratio;  
LAC = Lupus AntiCoagulant 
antibody;  
LDH = Lactate 
DeHydrogenase;  
MCV = Mean Corpuscular 
Volume;  
PT = Prothrombin Time;  
TAG = TriAcylGlycerol



©SEEd Tutti i diritti riservati
Clinical  Management  Issues   2011; 5(Suppl 2)78

An unusual case of secondary pure red cell aplasia (PRCA) that occults a squamous carcinoma of the tongue

subsequently radiotherapy. After radiothera-
py a hyperhaemia on the head and neck and 
dysfagia appeared.

During the following 6 months no tras-
fusion was necessary and the patient main-
tained the level of 9.5 g/dl of haemoglobin. 
Unfortunately, about 4 months after the 
patient had to receive transfusion every 20 
days.

dIsCussIon

The description of this case is useful to 
point out the polymorphic features of para-
neoplastic syndromes. In fact at the begin-
ning there were suspected symptoms of 
systemic lupus erythematosus (SLE) but the 
examinations did not meet all the criteria of 
the American College of Rheumathology 
(Table III).

Because of the above-mentioned symptoms 
a steroid therapy was given. Subsequently the 
patient was again admitted to the hospital 
for severe megaloblastic anaemia: radiolo-
gical, endoscopic, and serological investiga-
tions excluded causes of blood loss from the 
digestive tract, and eventual malabsorption 
and haemolysis.

The bone biopsy showed a series of red 
cell aplasia with a lymphoid infiltrate of 
reactive elements consistent with this his-
tological result; the patient was transferred 
to the Department of Haematology, where 
the investigations were completed with the 
study of cell cultures of the erythroid series, 
that showed no basal growth and stimula-
tion of growth factors, thus confirming the 
diagnosis of PRCA, but it was not yet clear 
if there was a primary or a secondary form 

on the periferic blood was negative. The cy-
togenetic revealed a XY karyotype. In bone 
marrow cultures there was a lack of growth 
of BFU-E (Burst Forming Unit-Erythroid) 
and CF U-GM (Colony Forming Unit-
Granulocyte, Macrofage).

Among the laboratory tests, the Parvovi-
rus B19, the HIV, the CMV, and the EBV-
Toxo Monotest were negative. There were 
no signs of haemolysis (LDH, haptoglobin, 
direct and indirect Coombs’ tests were nega-
tive, schistocytes not on peripheral blood) 
and not obvious signs (clinical and labora-
tory) of viral disease. The Epo-Hb electro-
phoresis was in range, tumour markers were 
normal, and proteinaemia and serum elec-
trophoresis were in range. After all examina-
tions, we diagnosed pure red cell aplasia.

In August 2009 we started immunosup-
pressive therapy with cyclosporin and pred-
nisone 25 mg + 200 mg + 250 mg/day with 
poor response (in fact the patient was trans-
fused with two bags of erythrocytes every 15 
days). From November 2009 to February 
2010 testosterone undecanoate 50 mg was 
added to cyclosporin, with haemoglobin lev-
els ranging from 7.2 and 8.9. In total, the 
patient was transfused with 40 bags of blood 
and ferritin 4,079 ng/dl.

The 2nd of February 2010 during the am-
bulatory monitoring appeared a swelling on 
the right laterocervical and on the tongue. 
Then the patient was sent to Maxillofacial 
Department where a biopsy was made and 
its specimen was later diagnosed of sq-
uamous cell carcinoma on the base of the 
tongue pN2b pT4. Subsequently he was 
submitted to subglottic laryngectomy + right 
lymphadenectomy + right laterocervical and 
then there was a plastic reconstruction and 

serositis Pleurisy, pericarditis on examination or diagnostic ECG or imaging
oral ulcers Oral or nasopharyngeal, usually painless; palate is most specific
arthritis Nonerosive, two or more peripheral joints with tenderness or swelling
photosensitivity Unusual skin reaction to light exposure
Blood disorders Leukopenia (< 4 × 103 cells/µl on more than one occasion), lymphopenia (< 1,500 cells/µl on more than 

one occasion), thrombocytopenia (< 100 × 103 cells/µl in the absence of offending medications), haemolytic 
anaemia

renal involvement Proteinuria (> 0.5 g/dl or 3+ positive on dipstick testing) or cellular casts
aNAs (antinuclear 
antibodies)

Higher titers generally more specific (> 1:160); must be in the absence of medications associated with 
drug-induced lupus

Immunologic phenomena Anti-double-stranded DNA, anti-Smith (Sm) antibodies; antiphospholipid antibodies (anticardiolipin 
immunoglobulin G (IgG) or immunoglobulin M (IgM) or lupus anticoagulant); biologic false-positive serologic 
test results for syphilis, lupus erythematosus (LE) cells (omitted in 1997)

neurologic disorder Seizures or psychosis in the absence of other causes
Malar rash Fixed erythema over the cheeks and nasal bridge, flat or raised
discoid rash Erythematous raised-rimmed lesions with keratotic scaling and follicular plugging, often scarring

table III
The 1982 American 
College of 
Rheumatology (ACR) 
criteria summarise 
features necessary to 
diagnose systemic lupus 
erythematosus (SLE).
They are summarised 
here with a useful 
mnemonic: the acronym 
“SOAP BRAIN MD”. 
The presence of 4 of 
the 11 criteria yields 
a sensitivity of 85% 
and a specificity of 
95% for SLE. It must 
be considered that 
individual features 
are variably sensitive 
and specific. Patients 
with SLE may present 
with any combination 
of clinical features and 
serologic evidence of 
lupus [7,8]



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Clinical  Management  Issues   2011; 5(Suppl 2) 79

M. Incagliato, A. Daffonchio, L. Celesti, A. Bottero, F. Balbi, M. D’Ulizia et al

A bone marrow biopsy control showed 
a slight increase of erythroid series: in this 
case we point out the absence in the litera-
ture of associations between pure red cell 
aplasia and squamous cell carcinoma of 
the tongue and that the removal of the tu-
mour, as it happens in many paraneoplastic 
syndromes, shows the improvement of the 
clinical picture.

In this case the improvement of anaemia 
is connected to debulky cancer, to cytokines 
and to antibodies produced by the tumour.

The diagnosis of a paraneoplastic syn-
drome (PNS) may precede, follow or be 
concurrent with the diagnosis of a malig-
nant tumour [9].

aCknowledgeMents

We acknowledge Professor Eugenia 
Nicolicchia for the article reviewing and 
the Nursing Team of the Internal Medicine 
Department for the collaboration and the 
data collection.

dIsClosure

The Authors declare that they have no 
financial competing interests.

of subclinical autoimmune disease (eryth-
roblastopenia in SLE).

In August 2009 the patient began a ther-
apy with prednisone 25 mg and cyclosporin 
600 mg/day; blood transfusions were re-
quired every 15 days, as the steroid therapy 
alone was not sufficient to maintain accept-
able levels of haemoglobin.

In November 2009 the patient received 
40 bags of transfused red cell concentrates 
and we decided therefore to associate also 
androgens (testosterone undecanoate) 50 
mg and if after three months there was an 
improvement of haemoglobin, he could have 
started the serum anti-lymphocyte.

In October 2010, because of the appear-
ance of laterocervical and lingual enlarged 
lymphnodes, the patient was transferred to 
the Department of Maxillofacial Surgery, 
where the biopsy was diagnosed with sq-
uamous cell carcinoma of the tongue pN2b 
pT4 (subglottic laryngectomy + right lym-
phadenectomy + right laterocervical with a 
plastic reconstruction); subsequently a ra-
diotherapy was performed.

After surgery the patient wasn’t trans-
fused for about 6 months. The haemoglob-
in maintained the values of 9-9.8 g/dl and 
then the haemotransfusion was performed 
every 20 days.

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