Could the use of appropriate diet help in the prevention of multiple myeloma?
The severity of the monoclonal gammopathy of
undetermined signifi cance (MGUS) is based on data
from a large epidemiologic study with a median follow-
up of 15.4 years, showing constant rate (1% per year)
of progression of MGUS to multiple myeloma. Pa-
tients were at risk even after 25 years or more of stable
MGUS, making life-long follow-up necessary [1,2].
Occurrence of “M” component in the sera of
patients with psoriasis, or psoriatic arthritis, like in
MGUS, has been reported , and it was stressed that
these patients can sometimes develop multiple myelo-
ma . We tested serum IgA and IgG immunoreactivity
to 3 food constituents and the presence of MGUS in an
83-year-old patient with psoriatic arthritis diagnosed in
2000, by ELISA and by electrophoresis and immuno-
fi xation. Cow’s milk proteins (CMP) (ICN Biomedicals,
Inc. Costa Mesa, USA), phytohemagglutinin P (PHA)
(INEP Zemun, Serbia) and gliadin (Binding Site, Bir-
mingham, UK) were used as antigens for ELISA tests.
The results indicated much enhanced IgA and IgG
immunoreactivity to CMP. Analysis of the patient’s
serum by electrophoresis and immunofi xation revealed
the presence of “M” component (monoclonal IgG (λ)
immunoglobulin; Figure 1A). When the patient learned
about his enhanced immunoreactivity to CMP, he de-
cid ed not to consume food with CMP. A month and
half after the start of CMP-free diet, analysis of serum
proteins was carried out. At that time, the patient had not
taken any immunosuppressive drugs.
Serum electrophoresis revealed disappearance of
the “M” component (Figure 1B). Also serum anti-CMP
IgG dropped from 892 AU/ml to 0 AU/ml (anti-CMP
IgA also dropped from 240 AU/ml to 0 AU/ml). Be-
sides, concentrations of total serum proteins and of IgG
were diminished after the CMP-free diet (Table 1).
Our results are in accordance with the data from
only one report dealing with a possible link between
disappearance of MGUS and gluten-free diet . In
conclusion, this analysis indicates the need for new
research aiming at answering whether special food
restriction diet for individuals with enhanced immunity
to some food constituent(s) would help manage the
now non-curable MGUS.
Journal of BUON 14: 321-325, 2009
© 2009 Zerbinis Medical Publications. Printed in Greece
LETTERS TO THE EDITOR
Figure 1. Serum protein electrophoresis and immunofixation.A:
“M” component before CMP-free diet; B: disappearance of “M”
component after CMP-free diet.
1. Kyle RA, Therneau TM, Rajkumar SV et al. A long-term
study of prognosis of monoclonal gammopathy of undeter-
mined signifi cance. N Engl J Med 2002; 346: 564-569.
2. Kyle RA, Rajkumar SV. Monoclonal gammopathy of unde-
termined signifi cance and smouldering multiple myeloma:
emphasis on risk factors for progression. Br J Haematol 2007;
3. Scherf I, Nahir M, Brick R, Joffe G, Tatarsky J. Monoclonal
IgG immunoglobulinemia in psoriatic arthritis. Dermato-
logica 1980; 160:348-350.
4. Peltonen L, Nikoskelainen E, Kätkä K, Tyrkkö J. Monoclonal
IgG immunoglobulinemia with subsequent myeloma in pso-
riatic arthritis. Dermatologica 1984; 169:207-210.
5. Pena AS, Nieuwkoop JV, Schuit HR, Hekkens WT, Haex AJ.
Transient paraproteinaemia in a patient with coeliac disease.
Gut 1976; 17:735-739.
Z. Juranic1, I. Besu1, M. Dajak2, A. Konic-Ristic3
1Department of Experimental Oncology, Institute of Oncology and Radi-
ology of Serbia, Belgrade;2Institute of Medicinal Biochemistry, Clinical
Center of Serbia, Belgrade;3Faculty of Pharmacy, University of Belgrade,
Correspondence to:Zorica Juranic, PhD. E-mail: firstname.lastname@example.org
Prolonged disease free survival with aggressive adjuvant chemotherapy in a case of
large cell neuroendocrine carcinoma of the uterine cervix
Table 1. Proteins in patient’s serum before CMP-free and after
Test 6/24/ 2008
CMP-free diet CMP-free diet
Electrophoresis With “M”
Without “M” Normal
IF “M” component
Total IgG (g/L)
Total IgA (g/L)
Total IgM (g/L)
Total proteins (g/l)
Anti CMP IgG (AU/mL)
Anti CMP IgA (AU/mL)
Anti PHA IgG (AU/mL)
Anti PHA IgA (AU/mL)
Anti gliadin IgG (IU/mL)
Anti gliadin IgA (IU/mL)
IF: immunofixation, CMP: cow’s milk protein
Large cell neuroendocrine carcinoma (LCNEC)
of the uterine cervix is a rare malignancy comprising
about only 0.6% of all cervical tumors, with a highly
aggressive biologic behavior and a clinical course fre-
quently characterized by early high regional recurrence
rate and widespread hematogenous metastases .
Many treatment modalities have been used, however
prognosis remains poor for both early and advanced
disease. Our experience is derived from a case of a 60-
year-old patient with large cell neuroendocrine cervical
tumor treated with radical surgery, followed by adju-
vant chemotherapy with cisplatin and etoposide (PE)
for 6 courses and consolidation radiotherapy. The pa-
tient remained free of tumor recurrence for 14 months.
Metastatic disease occurred in the lungs and liver and
was fi rst treated with PE and then with cisplatin/irino-
tecan without response and the patient succumbed to
her disease 18 months after initial diagnosis.
The basis of treatment of LCNEC of the uterine
cervix is derived from the therapy of cervical small cell
neuroendocrine carcinoma (SCNEC) and small cell
lung tumors. Initial surgical therapy in the form of radi-
cal hysterectomy with bilateral salpingo-oophorectomy
and lymph node dissection for the treatment of LCNEC
at early stages appears to be crucial predisposing to a
better prognosis, as long-term disease-free survival has
been reported only in patients with early-stage disease
treated with surgery . Chemotherapeutic regimens
used for the treatment of LCNEC usually follow those
of cervical and pulmonary SCNEC. Regimens contain-
ing cisplatin and etoposide and vincristine, adriamycin,
cyclophosphamide (VAC) offer survival advantage
and are more frequently used . Regarding the use
of radiation therapy, most clinicians prefer adjuvant
radiation even in early-stage disease. However, several
studies have failed to support the use of adjuvant radia-
tion, as patients receiving adjuvant radiation tended to
have a poorer prognosis in comparison with patients
receiving only adjuvant chemotherapy, while adjuvant
chemoradiation did not result in a better outcome when
compared to adjuvant chemotherapy alone [3,4].
According to our experience and the conclusions
of other studies it seems that patients with LCNEC of
the uterine cervix treated aggressively with adjuvant
chemotherapy might obtain a prolonged disease-free
interval since the role of radiotherapy is controversial
and warrants further investigation. Future reports and
studies may augment our experience and help improve
patients’ outcome by establishing better treatment
1. Sato Y, Shimamoto T, Amada S, Asada Y, Hayashi T. Large
cell neuroendocrine carcinoma of the uterine cervix: a clini-
copathological study of six cases. Int J Gynecol Pathol 2003;
2. Bermudez A, Vighi S, Garcia A, Sardi J. Neuroendocrine
cervical carcinoma: a diagnostic and therapeutic challenge.
Gynecol Oncol 2001; 82: 32-39.
3. Boruta DM, Schorge JO, Duska LA, Crum CP, Castrillon DH,
Sheets EE. Multimodality therapy in early-stage neuroendo-
crine carcinoma of the uterine cervix. Gynecol Oncol 2001;
4. Lee JM, Lee KB, Nam JH et al. Prognostic factors in FIGO
stage IB-IIA small cell neuroendocrine carcinoma of the
uterine cervix treated surgically: results of a multi-center
retrospective Korean study. Ann Oncol 2008; 19: 321-326.
M.C. Markopoulos1, A.A. Lagadas1, P. Alexandrou2
u u , K.C. Giannakopoulos1,
1Department of Gynecology,2Department of Pathology,3Medical Oncol-
ogy Unit, “Laiko” General Hospital, Athens University School of Medi-
cine, Athens, Greece
Correspondence to: Marios Markopoulos, MD. E-mail: mamarkop@med.
E-cadherin, b-catenin and topoisomerase II expression in rhabdomyosarcomas
E-cadherin, b-catenin and topoisomerase IIa
show increasing interest and have been subjected to
extensive investigation regarding their expression and
possible role in prognosis in soft tissue sarcomas [1-3].
We investigated the expression of these 3 molecules in
a small series of 6 primary, nonmetastatic rhabdomyo-
sarcoma (RMS) patients, median age 44 years. In 3
patients the tumor location was in the pelvis, in 2 pa-
tients in the orbit and in 1 patient in the cervical spine.
The median tumor size was 122 mm (range 6-220). All
RMSs were treated surgically with radical tumor exci-
sion. Adjuvant treatment was given to 3 patients (2
patients combined chemoradiotherapy and one postop-
Immunostaining was performed on formalin-
fixed, paraffin-embedded tissue sections using the
EnVision System (DAKO Corp, Netherlands), and the
monoclonal antibodies E-cadherin (CM170B, Biocare
Medical, California), b-catenin (DBS, Menarini, Hel-
las) and topoisomerase IΙa (Ki-S1, DAKO, ). Briefl y,
4μm-thick tissue sections were deparaffinized in
xylene, rehydrated through graded concentrations of
alcohol and heated in a microwave oven for 2 cycles
of 15 min each at 300W, in citrate buffer, for antigen
retrieval. Endogenous peroxidase activity was blocked
with H2O2solution in methanol (0.01M) for 30 min.
After washing with PBS for 5 min, the primary antibod-
ies CM170B (dilution 1:50), b-catenin (dilution 1:50)
and topoisomerase IΙa (dilution 1:50) were incubated
(30 min at room temperature). Then, the slides were
washed for 10 min with PBS and were visualized with
the EnVision system (DAKO) using diaminobenzidine
tetrahydrochloride as a chromogen (Sigma Fast DAB
tablets, St. Louis, Mo). Finally, all sections were coun-
terstained with hematoxylin. As a negative control,
the fi rst antibody was substituted with normal mouse
immunoglobulin of the same class. A semiquantitative
method was used for the evaluation of E-cadherin, b-
catenin and topoisomerase IIa. A level of over 20% cell
staining was regarded as the cut-off level of a tumor
expressing the above markers.
None of the examined RMSs showed E-cadherin
expression. Similarly, none of the RMSs had positive
nuclear b-catenin expression. Cytoplasmic b-catenin
expression was seen in 2 patients. Both of them had
strong expression of cytoplasmic b-catenin of 40% and
100%, respectively. Topoisomerase IIa was expressed
in all but one RMSs. All but one patient had strong
expression (range 50-90%). The two patients that had
positive b-catenin staining had high topoisomerase IIa
In RMSs absence of E-cadherin expression has
also been reported by Sato et al. who found that only
1 out of 12 RMSs had E-cadherin expression . This
absence can indicate either no involvement of this
molecule in the constitution of RMSs architecture, or
refl ect the aggressive behavior of these neoplasms.
Charrasse et al. showed a decrease in the expression
of cadherins family in all RMS-derived cell lines com-
pared to control cells . Our literature search did not
recognize any published data reporting on b-catenin
expression in RMSs. Finally, Coffi n et al. have found
that topoisomerase IIa expression decreased after
therapy and correlated with cytodifferentiation and
survival in the botryoid subtype . In conclusion, the
present report provides evidence regarding the expres-
sion of E-cadherin, b-catenin and topoisomerase IIa
in a small RMS population. Further evidence through
larger investigations is needed in order to confi rm our
results and to provide additional information of their
possible role in disease progression.
1. Sato H, Hasegawa T, Abe Y, Sakai H, Hirohashi S. Expression
of E-cadherin in bone and soft tissue sarcomas: a possible role
in epithelial differentiation. Hum Pathol 1999; 30: 1344-1349.
2. Hasegawa T, Yokoyama R, Matsuno Y, Shimoda T, Hirohashi
S. Prognostic signifi cance of histologic grade and nuclear
expression of beta-catenin in synovial sarcoma. Hum Pathol
2001; 32: 257-263.
3. Oda Y, Ohishi Y, Saito T et al. Nuclear expression of Y-
box-binding protein-1 correlates with P-glycoprotein and
topoisomerase II alpha expression, and with poor prognosis
in synovial sarcoma. J Pathol 2003; 199: 251-258.
4. Charrasse S, Comunale F, Gilbert E, Delattre O, Gauthier-
Rouvière C. Variation in cadherins and catenins expression
is linked to both proliferation and transformation of rhabdo-
myosarcoma. Oncogene 2004; 23: 2420-2430.
5. Coffi n CM, Rulon J, Smith L, Bruggers C, White FV. Patho-
logic features of rhabdomyosarcoma before and after treat-
ment: a clinicopathologic and immunohistochemical analysis.
Mod Pathol 1997; 10: 1175-1187.
P.N. Gogou1, A. Batistatou2, E.E. Pakos1, N. Apostolikas3, D. Stefanou2,
1Department of Radiation Therapy, and 2Department of Pathology, Uni-
versity of Ioannina, Medical School, Ioannina; 3Department of Pathology,
St Savvas Anticancer-Oncologic Hospital, Athens, Greece
Correspondence to: Emilios E. Pakos. Neohoropoulo, POB: 243, Ioannina,
45500, Greece. E-mail: email@example.com
An unusual case of recurrent non-Hodgkin’s lymphoma presented with massive
ascites, peritoneal involvement and elevated CA-125 level
Simultaneous occurrence of massive ascites and
non-Hodgkin’s lymphoma (NHL) has been rarely
documented ; only one case with peritoneal NHL
and elevated CA-125 levels has been previously docu-
mented in the English medical literature . Several
studies suggested that CA-125 levels in NHL patients
may be helpful in predicting disease activity [3,4].
A 70-year-old male was admitted to our hospital
with a history of stuffiness in March 2002. Stage IE
diffuse large B cell NHL of the nasopharynx was con-
fi rmed from a biopsy taken from a polypoid mass which
extended into the posterior end of the nasal cavity. The
tumor was Ki-67 (+) in 70% of cells, CD20 (+) and CD3
(– ( ( ). One cycle of chemotherapy \with cyclophosphamide –
and vincristine was administered along with radiotherapy
(4500cGy) to the nasopharynx during a one-month pe-
riod. Cervical, thoracic and abdominal CT scans and bio-
chemical parameters showed complete response (CR).
One year later he was hospitalized with 2-month
history of fatigue, anorexia, and progressive enlarge-
ment of waist circumference. On physical examination,
he had massive ascites and decreased respiratory sounds
of the lung bases bilaterally. There was no lymphade-
nopathy. Splenomegaly (3 cm) was noted in the midcla-
vicular line. The initial lab work-up showed white blood
cell (WBC) count 27,400/m3, hemoglobin 13.7 g/dL,
hematocrit 40%, platelet count 95,000/m3, erythrocyte
sedimentation rate 65 mm/h, urea 124 mg/dL (10-50),
creatinine 1.86 mg/dL (0.50-1.50), uric acid 16.9 mg/dL
(3.4-7.0), sodium 127 mEq/L (135-145) potassium 5.3
mEq/L (3.5-5.0), LDH 1271 U/mL (98-192), and CA-
125 857 U/mL (1.7-32.0). Other lab tests were within
normal range. The patient was hydrated and allopurinol
therapy was initiated. These parameters returned to
normal ranges on day 15.
On the 5th day of hospitalization, WBC increased
to 51,400/m3 and peripheral blood smears revealed
atypical mononuclear cells that increased from 20% to
74%. On immunohistochemistry (IHC), Sudan-Black
and PAS stainings were negative. CD5 (+) clonal B
cell population which weakly expressed CD23 was
detected on peripheral blood. Ascitic fl uid was exudate.
WBC count was 21,000/mm3and 90% of the cells were
atypical mononuclear cells. Cytology of the ascitic fl uid
showed a large number of immature monomorphic lym-
phoid cells, attributable to NHL infi ltration. Thorax and
abdominal CT scan revealed bilateral pleural effusion,
splenomegaly, infarction at the lower and middle region
of spleen, multiple intraabdominal conglomerated nodal
packs, massive ascites, and diffuse peritoneal implants.
On the 10th day of admission combination chemo-
therapy with cyclophosphamide 750 mg/m2 and vin-
cristine 1.4 mg/m2, both on day 1, was administered.
Doxorubicin and prednisone were not administered
due to cardiac dysfunction, urate nephropathy and
hematemesis. The initial WBC count of 64,000/mm3
decreased to 7,100/m3 on day 10 of chemotherapy. CA-
125 level dropped from 857 to 205 U/mL on day 20.
Waist circumference decreased considerably. Six cycles
were administered with complete clinical and labora-
tory remission. He remains in CR 6 years thereafter.
Peritoneal involvement in NHL is about 1-3% .
Because the omentum lacks lymphoid elements, lym-
phomatous infi ltration is uncommon. In a study, perito-
neal involvement has been found in only 4 patients .
In studies with respect to NHL and CA-125, CA-125
has been considered to be an indicator of peritoneal sti-
mulation evoked by tumoral invasion rather than a di-
rect tumoral product. It has also been reported as an
important marker in monitoring treatment and follow-
up of patients with NHL and coexisting peritoneal in-
volvement and ascites , in staging and assessing tu-
mor activity and in predicting decreased survival.In our
case, pretreatment CA-125 levels were fairly elevated
(857 U/mL), gradually decreased and returned to nor-
mal on the 3rd month of treatment.
In patients with NHL who have massive ascites
and elevated CA-125 level, recurrent NHL with perito-
neal involvement should be considered in the differen-
1. Vakar-Lopez F, Yang M. Peripheral T-cell lymphoma present-
ing as ascites: a case report and review of the literature. Diagn
Cytopathol 1999; 20: 382-384.
2. Horger M, Muller-Schimpfle M, Yirkin I, Wehrmann M,
Claussen CD. Extensive peritoneal and omental lymphoma-
tosis with raised CA 125 mimicking carcinomatosis: CT and
intraoperative fi ndings. Br J Radiol 2004; 77: 71-73.
3. Ozguroglu M, Turna H, Demir G et al. Usefulness of the epi-
thelial tumor marker CA 125 in non-Hodgkin’s lymphoma.
Am J Clin Oncol 1999; 22: 615-618.
4. Glazer HS, Lee JK, Mauro MA, Griffi th R, Sagel SS. Non-
Hodgkin’s lymphoma: computed tomographic demonstration
of unusual extranodal involvement. Radiology 1983; 149:
5. Zacharos ID, Efstathiou SP, Georgiou G et al. The prognostic
signifi cance of CA 125 in patients with non-Hodgkin’s lym-
phoma. Eur J Haematol 2002; 69: 221-226.
A. Doventas1, I. Yildiz2, T. Toptas3, Z. Baslar4, A. Bilici5,
1Department of Geriatrics, Istanbul Education and Research Hospital,
Istanbul; 2Department of Internal Medicine, Cerrahpasa Medical Faculty,
Istanbul University, Istanbul; 3Department of Hematology, Marmara Uni-
versity, Medical Faculty, Istanbul; 4Department of Hematology, Cerrahpasa
Medical Faculty, Istanbul University, Istanbul;5Department of Medical
Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Is-
tanbul;6Department of Geriatrics, Cerrahpasa Medical Faculty, Istanbul
University, Istanbul, Turkey
Correspondence to: Ahmet Bilici, MD. E-mail: firstname.lastname@example.org