A Case of Metastatic Uterine Tumor Originating from Small-Cell Lung Cancer (SCLC) Mimicking Uterine Sarcoma

Abstract

Metastatic uterine tumors originating from extragenital cancers are a rare clinical occurrence. We report a case of metastatic uterine cancer derived from small-cell lung cancer (SCLC) that necessitated surgical treatment. The patient was a 59 y/o female who had undergone chemotherapy for stage IIIB SCLC. A 15 cm uterine tumor lesion was initially detected on CT scans. The patient had previously been diagnosed with uterine fibroids, but compared to the most recent CT scans taken one and a half months earlier, imaging diagnosis revealed a sudden increase in the size of the tumor when compared to the 8 cm myoma fibroid noted previously. Additional work-up with MRI scans revealed T2-enhanced images of a tumor that had almost completely invaded the myometrium; the tumor presented with marked diffusion-weighted enhancement, and a flow void was noted within the tumor. A differential diagnosis of uterine sarcoma was considered, but due to the lack of focal hemorrhage or necrosis findings on MRI imaging, the possibility of differential diagnosis of metastatic SCLC was also noted. As the patient was experiencing abdominal symptoms including abdominal distension and tenderness due the tumor, a simple hysterectomy and bilateral salpingo-oophorectomy were performed to palliate the symptoms. During the surgical procedures, intra-abdominal findings noted peritoneal dissemination while intraoperative cell cytology diagnosis of ascites revealed small-cell cancer. The final histopathological diagnosis likewise revealed metastatic small-cell cancer from the primary lung cancer. The clinical status of the lung cancer was evaluated as progressive disease (PD), and a change in chemotherapy regimen was necessitated. Further disease progression was noted on CT scans at 2 and a half months after surgery, and with gradual systemic disease progression, the patient died of disease at 3 months postsurgery. Initial evaluation of rapidly enlarging uterine tumors should include a differential diagnosis of uterine sarcoma; additionally, it is necessary to also consider the rare possibility of metastatic disease as in the present case with a clinical history of extragenital malignancy.

1. Introduction
Metastatic uterine tumors originating from extragenital cancers are rare [1–3], while even more rare are uterine metastases from lung cancer [4]. We report a case of a rapidly enlarging uterine tumor discovered during treatment of lung cancer, which, while requiring a differential diagnosis from uterine sarcoma, was eventually diagnosed as metastatic uterine cancer derived from small-cell lung cancer (SCLC).

2. Case Presentation
The patient was 59 y/o female, gravida 3 para 3 with menopause at 55 y/o. She had been diagnosed with stage IIIB SCLC (cT2aB3N0) and had been undergoing chemotherapy and radiation treatment. Radiation treatment consisted of 60 Gy to the mediastinum while chemotherapy had been initiated with (100 mg/m²); however, after 11 courses, lymph node swelling to the supraclavicular nodes was noted and subsequent chemotherapy regimen was changed to amrubicin. Additional swelling of the supraclavicular lymph nodes after 5 additional courses necessitated a further change in chemotherapy to .
One year and 10 months following initiation of chemotherapy, the patient noted increasing lower abdominal pain and an enhanced CT scan was performed. Initial imaging diagnosis demonstrated an infection of a degenerated uterine fibroid which was treated conservatively with antibiotics. An increase in LDH was noted on biochemical profile after 2 months, while a follow-up CT revealed an increase in size of the uterine tumor, leading to a gynecologic consultation. At initial pelvic examination, a uterine tumor of neonatal head size with moderate pelvic motility as well as slight serous-yellowish vaginal discharge was noted.
Hematological examinations revealed a complete blood count consisting of Hb 9.0 g/dl, Plt , WBC 6000/μl, and biochemical profiles consisting of CRP 2.34 mg/dl, LDH 4100 U/l, D-dimer 9.8 μg/ml, and NSE 733 ng/ml. Uterine cervical and endometrial cytology were both negative.
On CT imaging diagnosis, a sudden increase in the size of the uterine tumor compared to CT scans taken 6 weeks earlier was observed (Figure 1), but no other apparent metastatic lesions were noted. Pelvic MRI revealed multiple uterine fibroid nodules, as previously diagnosed, were noted. The tumor demonstrated T2-enhanced images and also presented with marked diffusion-weighted enhancement, and a flow void was noted within the tumor. The endometrium as well as cervical epithelium was intact, and there was also a lack of focal hemorrhage or necrotic findings (Figure 2). Based upon these findings, primary uterine sarcoma was considered, but the possibility of differential diagnosis of metastatic SCLC was also noted. Due to the increasing abdominal symptoms, including abdominal distension and tenderness due to the tumor, a simple hysterectomy and bilateral salpingo-oophorectomy were performed. Intra-abdominal findings revealed extrauterine dissemination consisting of large nodular serosal spread, and multiple sites of peritoneal dissemination were likewise noted. Macroscopically, the uterine endometrium was smooth and there was no spread of the uterine tumor to either the adnexa or to the uterine cervix (Figure 3). Ascitic cytology was class V, assumed small-cell carcinoma.

(a)

Full text

Case Report
A Case of Metastatic Uterine Tumor Originating from Small-Cell
Lung Cancer (SCLC) Mimicking Uterine Sarcoma
Mariko Fujima,
1
Yoichi Kobayashi ,
1
Momoe Watanabe,
1
Hiromi Shibuya,
1
Hironori Matsumoto,
1
Yoshiko Nishigaya,
1
Mai Momomura,
1
Shinya Yoshiike ,
2
Kiyotaka Nagahama ,
2
Junji Shibahara ,
2
and Atsushi Suzuki
3
1
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Japan
2
Department of Pathology, Kyorin University School of Medicine, Japan
3
Department of Obstetrics and Gynecology, Kosei Hospital, Japan
Correspondence should be addressed to Yoichi Kobayashi; yoichi@ks.kyorin-u.ac.jp
Received 10 April 2021; Accepted 15 July 2021; Published 24 July 2021
Academic Editor: Kyousuke Takeuchi
Copyright © 2021 Mariko Fujima et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Metastatic uterine tumors originating from extragenital cancers are a rare clinical occurrence. We report a case of metastatic uterine
cancer derived from small-cell lung cancer (SCLC) that necessitated surgical treatment. The patient was a 59 y/o female who had
undergone chemotherapy for stage IIIB SCLC. A 15 cm uterine tumor lesion was initially detected on CT scans. The patient had
previously been diagnosed with uterine fibroids, but compared to the most recent CT scans taken one and a half months earlier,
imaging diagnosis revealed a sudden increase in the size of the tumor when compared to the 8 cm myoma fibroid noted
previously. Additional work-up with MRI scans revealed T2-enhanced images of a tumor that had almost completely invaded
the myometrium; the tumor presented with marked diffusion-weighted enhancement, and a flow void was noted within the
tumor. A differential diagnosis of uterine sarcoma was considered, but due to the lack of focal hemorrhage or necrosis findings
on MRI imaging, the possibility of differential diagnosis of metastatic SCLC was also noted. As the patient was experiencing
abdominal symptoms including abdominal distension and tenderness due the tumor, a simple hysterectomy and bilateral
salpingo-oophorectomy were performed to palliate the symptoms. During the surgical procedures, intra-abdominal findings
noted peritoneal dissemination while intraoperative cell cytology diagnosis of ascites revealed small-cell cancer. The final
histopathological diagnosis likewise revealed metastatic small-cell cancer from the primary lung cancer. The clinical status of the
lung cancer was evaluated as progressive disease (PD), and a change in chemotherapy regimen was necessitated. Further disease
progression was noted on CT scans at 2 and a half months after surgery, and with gradual systemic disease progression, the
patient died of disease at 3 months postsurgery. Initial evaluation of rapidly enlarging uterine tumors should include a
differential diagnosis of uterine sarcoma; additionally, it is necessary to also consider the rare possibility of metastatic disease as
in the present case with a clinical history of extragenital malignancy.
1. Introduction
Metastatic uterine tumors originating from extragenital can-
cers are rare [1–3], while even more rare are uterine metasta-
ses from lung cancer [4]. We report a case of a rapidly
enlarging uterine tumor discovered during treatment of lung
cancer, which, while requiring a differential diagnosis from
uterine sarcoma, was eventually diagnosed as metastatic uter-
ine cancer derived from small-cell lung cancer (SCLC).
2. Case Presentation
The patient was 59 y/o female, gravida 3 para 3 with
menopause at 55 y/o. She had been diagnosed with stage IIIB
SCLC (cT2aB3N0) and had been undergoing chemotherapy
and radiation treatment. Radiation treatment consisted of
60 Gy to the mediastinum while chemotherapy had been ini-
tiated with cisplatin ð80 mg/m2Þ+ etoposide (100 mg/m
2
);
however, after 11 courses, lymph node swelling to the
Hindawi
Case Reports in Obstetrics and Gynecology
Volume 2021, Article ID 1809017, 4 pages
https://doi.org/10.1155/2021/1809017

supraclavicular nodes was noted and subsequent chemo-
therapy regimen was changed to amrubicin. Additional
swelling of the supraclavicular lymph nodes after 5 addi-
tional courses necessitated a further change in chemother-
apy to carboplatin + paclitaxel.
One year and 10 months following initiation of chemo-
therapy, the patient noted increasing lower abdominal pain
and an enhanced CT scan was performed. Initial imaging
diagnosis demonstrated an infection of a degenerated uterine
fibroid which was treated conservatively with antibiotics. An
increase in LDH was noted on biochemical profile after 2
months, while a follow-up CT revealed an increase in size
of the uterine tumor, leading to a gynecologic consultation.
At initial pelvic examination, a uterine tumor of neonatal
head size with moderate pelvic motility as well as slight
serous-yellowish vaginal discharge was noted.
Hematological examinations revealed a complete blood
count consisting of Hb 9.0 g/dl, Plt 12:1 × 10,000/μl, WBC
6000/μl, and biochemical profiles consisting of CRP
2.34 mg/dl, LDH 4100 U/l, D-dimer 9.8 μg/ml, and NSE
733 ng/ml. Uterine cervical and endometrial cytology were
both negative.
On CT imaging diagnosis, a sudden increase in the size of
the uterine tumor compared to CT scans taken 6 weeks ear-
lier was observed (Figure 1), but no other apparent metastatic
lesions were noted. Pelvic MRI revealed multiple uterine
fibroid nodules, as previously diagnosed, were noted. The
tumor demonstrated T2-enhanced images and also presented
with marked diffusion-weighted enhancement, and a flow
void was noted within the tumor. The endometrium as well
as cervical epithelium was intact, and there was also a lack
of focal hemorrhage or necrotic findings (Figure 2). Based
upon these findings, primary uterine sarcoma was consid-
ered, but the possibility of differential diagnosis of metastatic
SCLC was also noted. Due to the increasing abdominal
symptoms, including abdominal distension and tenderness
due to the tumor, a simple hysterectomy and bilateral
salpingo-oophorectomy were performed. Intra-abdominal
findings revealed extrauterine dissemination consisting of
large nodular serosal spread, and multiple sites of peritoneal
dissemination were likewise noted. Macroscopically, the
uterine endometrium was smooth and there was no spread
of the uterine tumor to either the adnexa or to the uterine
cervix (Figure 3). Ascitic cytology was class V, assumed
small-cell carcinoma.
Histopathological diagnosis revealed the tumor was noted
to have invaded almost the entire myometrium of the uterus
and demonstrated tumor proliferation with marked lymph
vascular space invasion. The tumor demonstrated invasion
to close to the serosal surface and localized invasion to the
endometrial cavity while no cervical invasion was noted. Dis-
seminated abdominal lesions demonstrated similar pathologi-
cal features to the uterine tumor. The endometrium was
mostly atrophic. Immunohistochemical profiles of the tumor
revealed partial positivity to CD56,slightpositivity to synapto-
physin, negativity to chromogranin A, positivity to NSE,
partial positivity to AE1/3 and EMA, and negativity to vimen-
tin. Based upon these findings, the final histopathological
diagnosis was metastatic small cell carcinoma of the uterus
originating from the primary lung cancer (Figure 4).
(a) (b)
(c)
Figure 1: Preoperative pelvic CT findings: (a) 1 year and 6 months after initiation of treatment: myoma fibroids were noted; (b) 1 year and
10 months after initiation of treatment: the patient experienced abdominal pains, and imaging diagnosis demonstrated an infection of a
degenerated myoma uteri fibroid; (c) 2 years after initiation of treatment: elevated serum D-dimer and LDH were noted, and imaging
diagnosis noted a differential diagnosis of uterine sarcoma or uterine metastasis from lung cancer.
2 Case Reports in Obstetrics and Gynecology

The clinical status of the lung cancer was evaluated as
progressive disease (PD), and although chemotherapy
regimen was changed to carboplatin + irinotecan, 2 and a
half months after surgery, further disease progression was
observed on CT scans consisting of multiple liver metastases,
increasing peritoneal dissemination lesions, and increasing
pleural effusion. The patient died of disease at 3 months
postsurgery.
3. Discussion
Metastatic uterine tumors are rare and comprise only 0.001-
0.1% of all malignant uterine tumors [1]. A report of 63 cases
of extragenital cancers metastasizing to genital organs found
the following breakdown in origin: breast (42.9%), colon
(17.5%), gastric and pancreatic (11.1%), gall bladder and lung
(4.8%), malignant melanoma and bladder (3.2%), and thy-
roid (1.6%) [2]. Metastases from lung cancer to the female
genital tract are extremely rare. Recently, Sevinyan et al.
reported there were only 6 cases of lung cancers metastasiz-
ing to female genital tract including their case [5]. So, repre-
sent case is the seventh one, and so far, as we investigated,
this is the first report of metastatic uterine tumor originating
from SCLC.
The following hypotheses [6] have been described to
account for the low incidence of metastatic spread from the
lungs to the uterus: (1) the possibility that the sharp anatomic
angle of the internal iliac artery leading to the uterine artery
makes hinders hematogenic metastasis to the uterus; (2) the
possibility that the contractive movements of the uterine
myometrium prevent attachment of metastatic cells; (3) the
possibility that the oxygen levels and pH within uterine tissue
are not suitable for tumor attachment. However, none of
these hypotheses have been clinically determined.
Although a malignant uterine tumor may be suspected
from preoperative imaging diagnoses, the final diagnosis of
metastatic tumor is most often diagnosed from postsurgical
pathological specimens. In the present case, the uterine
tumor did not present with focal necrotic or hemorrhagic
findings on MRI imaging, but elevated NSE levels suggesting
metastatic SCLC were noted, and the possibility of a metasta-
tic tumor was strongly suspected preoperatively. If the meta-
static tumor has invaded the endometrium and if there is a
positive tumor biopsy on endometrial biopsy, it is possible
to present with a differential diagnosis of metastatic tumor
preoperatively; however, as in the present case, when the
(a) (b)
(c) (d)
Figure 2: Pelvic MRI imaging: (a) T1-enhanced images; (b) T2-enhanced images; (c) ADC map b = 1000; (d) diffusion-weighted images. The
tumor demonstrated moderate to strong T2-enhanced images; marked diffusion-weighted enhancement was noted on the tumor that had
almost completely invaded the uterine myometrium.
Figure 3: Macroscopic finding during surgery. Large diffuse
nodular disseminated tumors were noted on the serosal surface of
the uterus.
3Case Reports in Obstetrics and Gynecology

tumor has not invaded the endometrium [7], a preoperative
histopathological diagnosis is often clinically difficult.
In general, metastasis to the uterus often occurs by lym-
phogenic or hematogenic routes, by direct invasion of perito-
neal dissemination to the uterine serosa, and by retrograde
invasion of malignant ascites through the fallopian tubes.
We surmise that due to the peritoneal dissemination noted
in the present case, metastatic spread to the uterus was most
probably caused by tumor spread from dissemination. How-
ever, as the pathological findings noted a diffuse spread of the
metastatic lesion throughout the uterine myometrium as well
as direct serosal invasion, the possibility of hematogenic
spread to the uterine myometrium must also be considered.
Sometimes, it is very difficult to determine whether surgi-
cal treatment should be indicated or not for the present case.
In our case, uterine fibroma has rapidly grown in size, and
also, the patient had abdominal distention and tenderness.
So, in order to confirm the pathological diagnosis of uterine
tumor as well as to relieve the patient’s symptoms, surgical
treatment was selected. When the patient presents with
severe abdominal symptoms, as in our present case, aggres-
sive surgical treatment may be indicated to improve the
patient’s QOL; however, there is little evidence whether
removal of such bulky metastatic tumor could improve
survival prognosis [4], so further evidences should be
accumulated.
4. Conclusion
We report a case of metastatic uterine cancer originating
from SCLC that presented with a clinical presentation that
necessitated differential diagnosis from primary uterine sar-
coma. In order to assess appropriate treatment strategies, a
clinical presentation of rapidly enlarging uterine tumors
should always include a differential diagnosis of primary
uterine sarcoma, but when presented with a history of extra-
genital malignancies, it is important to also include a differ-
ential diagnosis of the rare possibility of metastatic disease.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
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(a) (b)
Figure 4: Postoperative pathological findings: (a) HE stain: tumor cells with increased chromatin, enlarged nuclei, lightly acidic cytoplasm,
and increased N/C ratios were noted to proliferate in a solid nest. Localized geographic necrosis was also observed. (b) Immunohistochemical
finding: the tumor demonstrated positivity for neurosecretory tumor profiles including partial positivity for CD 56, slight positivity for
synaptophysin, and negativity for chromogranin A. The immunohistochemical profile was similar to that of the primary lung cancer.
4 Case Reports in Obstetrics and Gynecology