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Gynecologic Oncology

Case Report

Neoadjuvant combined chemotherapy followed by external

whole pelvic irradiation in two cases of primary extranodal

non-Hodgkin’s lymphoma of the uterine cervix

Fernando Heredia*, Marco Bravo, Mateo Pierotic, Alejandro Majlis, Leonardo Carmona

Instituto Clinico Oncologico de la Fundacion Arturo Lopez Perez, Santiago de Chile, Chile

Received 22 October 2004

Abstract

Background. Primary extranodal lymphomas of the genital tract are rare.

Cases. As there is no current consensus in its management, we present two further cases and their treatment with neoadjuvant

chemotherapy, followed by radiation therapy. A radical hysterectomy with bilateral pelvic lymphadenectomy was performed after primary

treatment in one case. Clinical response was complete in both cases and pathological response was documented in one.

Conclusions. Complete response of these lymphoid neoplasms can be achieved by neoadjuvant chemotherapy followed by external

irradiation.

D 2004 Elsevier Inc. All rights reserved.

Keywords: Cervical lymphoma; Neoadjuvant chemotherapy and pelvic irradiation; Primary extranodal non-Hodgkin’s lymphoma

Introduction

The genital tract as primary site of malignant lymphoma

in women is extremely rare. It is accepted that 1 in 175

extranodal lymphomas in women is likely to originate in the

vagina, uterus or cervix [1].

As there is no current consensus in management, diverse

protocols have been used with varied results [1–10].

We report 2 cases treated and followed in our institution

between 1999 and 2004, with neoadjuvant chemotherapy

followed by external pelvic irradiation and radical surgery in

one of them. Complete clinical response was achieved in

both patients.

Case reports

Patient 1 is a 32-year-old white nulligravida who

presented in August 1999 with a two and a half month

0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.ygyno.2004.12.018

* Corresponding author.

E-mail address: herediaf@falp.org (F. Heredia).

history of bloody vaginal discharge and postcoital vaginal

bleeding. Her previous cervical cytology exam was normal.

A bulky endophytic 6 cm cervical mass was noted on pelvic

examination. The tumor invaded the upper third of the

vagina and both parametriums without compromising the

pelvic sidewall. Therefore, FIGO stage IIb tumor was

diagnosed. Punch biopsy was performed and preliminary

histopathology classified the tumor as an undifferentiated

small cell carcinoma or a lymphoma. Immunohistochemical

study was ordered. Meanwhile, chest, abdominal and pelvic

CT scans showed a solid 8 cm lesion on the uterine cervix

and no evidence of metastatic disease. Two days later, she

presented with massive vaginal bleeding that was controlled

by bilateral extraperitoneal hypogastric artery ligation.

Immunohistochemical study showed CD20 and antileuko-

cyte common antigen positivity but CD30, CD45Ro and

pancytokeratine stainings were negative. Final pathological

diagnosis was primary diffuse mixed small and large B-cell

non-Hodgkin’s lymphoma according to the WHO classi-

fication. Bone marrow biopsy showed no evidence of

lymphoma. Ann-Arbor Stage IEA was diagnosed. She was

then treated with 3 cycles of CHOP with complete remission

97 (2005) 285–287

F. Heredia et al. / Gynecologic Oncology 97 (2005) 285–287286

at clinical examination and pelvic CT scan. Chemotherapy

was followed by external whole pelvis irradiation with

Cobalt 60 (four-field box technique), for a total dose of

4500 cGy. She remains disease free 61 months after the

initial diagnosis.

Patient 2 is a 31-year-old white gravida 1 para 1 woman

who presented in July 2003 with a 2 month history of

vaginal bloody discharge. Her previous cervical cytology

exam was normal. Colposcopic examination revealed an

enlarged cervix. Vaginal ultrasound found a 93 � 70 mm

central cervical mass. Punch biopsy was performed and

pathological examination confirmed a non-Hodgkin lym-

phoma. Further immunohistochemical study showed CD20

positivity but CD3 staining was negative. Final pathological

diagnosis was primary diffuse mixed small and large B-cell

non-Hodgkin’s lymphoma of the uterine cervix, according

to the WHO classification. Computed tomographic scan of

the chest, abdomen and pelvis showed a soft tissue cervical

tumor and right pelvic adenopaties. Bone marrow biopsy

was negative for lymphoma. Ann-Arbor stage IIEA was

diagnosed. She started neoadjuvant chemotherapy with

m-CHOP protocol every 28 days for four cycles. Abdominal

and pelvic CT scan showed no evidence of disease. As

planned, external whole pelvis radiation was administered

with Cobalt 60 (four-field box technique), for a total dose of

3600 cGy. Five weeks after finishing her radiation therapy,

estrogenic cervical mucus was noted at the time of pelvic

examination. The potential for microscopic residual tumor

in the cervix or regional lymph nodes was considered, and

radical hysterectomy with bilateral lymph node dissection

was offered. Surgery was performed 6 weeks after

completion of primary therapy with no incidents. Histo-

pathologic evaluation of cervix, parametriums and lymph

nodes confirmed complete response. She remains with no

evidence of recurrent disease 15 months after the initial

diagnosis.

Discussion

Only one third of malignant lymphomas is extranodal [3].

Primary lymphomas of the female genital tract are rare. 1 of

175 extranodal lymphomas is likely to originate from the

vagina, uterus or cervix [1]. The uterine cervix is the most

common primary location in the genital tract, whereas the

ovary is the most common metastatic site for lymphomas

[2–4]. The incidence of primary malignant lymphoma of the

uterine cervix is unknown but it has been estimated between

0.412–0.6% of the non-Hodgkin’s lymphomas in women

[2,5,10]. The median age of presentation is in the fourth

decade [6,10]. The most frequent histology is the diffuse

large B-cell non-Hodgkin’s lymphoma of the WHO classi-

fication [3,7,8]. The most common complaint is abnormal

vaginal discharge, almost always bloody [1,3,5]. It usually

presents as a rapidly growing lesion, accompanied by a

feeling of pelvic pressure [6]. Although most of these tumors

are larger than other cervical tumors at diagnosis, diffe-

rentials should include scamous cell carcinoma (especially

bbarrel-shapedQ or ulcered lesions), cervical fibroid, cervical

sarcoma and small-cell carcinoma [1,5]. As they are seldom

present with ulceration, cervical cytology exam is rarely

positive [4]. This situation makes cervical punch biopsy and

immunohistochemical studies indispensable for diagnosis.

Besides a complete physical examination searching for

enlarged peripheral lymph nodes, the extension study should

always include chest, abdominal and pelvic CT scans along

with bone marrow biopsy.

Treatment of primary lymphoma of the uterine cervix

has been subject of discussion for a long time. Radio-

therapy alone or in combination with chemotherapy or

radical surgery was the first reported approach to this

pathology [3,4,6,9]. More recently, attention has been

given to neoadjuvant combination chemotherapy alone or

followed by surgery [1,3–5,8,9]. Besides preservation of

reproductive potential, combination chemotherapy has the

advantage of reducing tumor volume which makes

subsequent surgery simple. It also might prevent micro-

metastasis while preserving ovarian function, which is

critical in younger patients [4,5]. Despite their age and

the fact that complete clinical and radiological response

was noted after combination chemotherapy, our two cases

were treated with neoadjuvant chemotherapy followed by

radiation therapy. This was done for two main reasons:

(1) both patients asked for definitive treatment for their

tumor, even if their fertility or ovarian function was

compromised; (2) we believe that an insufficient number

of woman with primary malignant lymphoma of the

uterine cervix have been treated with combination chemo-

therapy alone to make solid comparisons with more

conventional modalities of radiation therapy and/or

surgery.

Prognosis seems to correlate with the stage of the lesion.

The prognostic significance of the different histological

types and of the various treatment methods is still unclear.

An overall 5-year survival rate of 77% was reported for 18

cases of cervical lymphomas [2]. Prognosis is still conside-

red to be good in extensive local disease, namely, FIGO

stage II and III tumors [10].

Recently, targeted therapy using Rituximab, a mono-

clonal antibody directed against CD20 antigen which is

expressed by most non-Hodgkin’s lymphomas, has been

used along with highly active antiretroviral therapy

(HAART) and combination chemotherapy, in cases of

HIV-associated non-Hodgkin’s lymphomas with promising

results. Rituximab should then be considered as another tool

for the treatment of these malignancies [7,8].

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