Case presentation
A 56-year-old male presented to our hospital with ”dizziness” and was
found to have a 4.2*3.7 cm occupancy in the lower lobe of the left lung
with obstructive atelectasis and enlarged mediastinal and
supraclavicular lymph nodes on chest CT(figures 1a1,a2,a3). No distant
metastasis was found in the head MRI, abdominal CT and SPECT bone scan.
To further clarify the pathological type of the lung mass, a
percutaneous puncture biopsy was performed on 01/17/2020.
Immunohistochemical demonstrated strong and diffuse expression of PCK,
P40 and CK5/6 There was focal expression of TTF-1 and Syn, whereas
EBER1/2-ISH, CK7, NapsinA and CgA were negative(figures 2a,b). And no
driver mutation was detected. The diagnosis of NC was confirmed
following fluorescence in-situ hybridization (FISH) showed BRD4-NUT
rearrangement. PD-L1 testing was not performed due to insufficient
specimens. He was finally diagnosed as NUT carcinoma of the lower lobe
of the left lung with hilar, mediastinal, and supraclavicular lymph node
metastases, T3N3M0, stage IIIC(American Joint Committee on Cancer 8th
Edition Cancer Staging Form). Patient refuses surgery. Cycle 1
nab-paclitaxel combined with carboplatin chemotherapy was then started
on February 12, 2020. Chest CT was done to evaluate the efficacy before
next cycle and suggested heterogeneous changes with a shrinking chest
lesion and an increasing supraclavicular lymph node lesion(figures 1
b1,b2,b3). Supraclavicular lymph node aspiration biopsy was performed at
the same time as the second cycle of chemotherapy. Pathological findings
showed poorly differentiated carcinoma in fibrofatty tissue, and FISH
detected NUT gene translocation, indicating NC metastasis. Then chest
and neck radiotherapy (56Gy/28f) was performed from March 16, 2020 to
May 11, 2020, the target volume was preventability lymph node area
radiation(accessory figure1).
Radiotherapy was suspended for 5 days for skin erosion of the neck
caused by radiation during treatment. The 3rd and 4th cycles of
chemotherapy were administered concurrently with radiotherapy. After the
completion of radiotherapy, chest CT scan showed significant response of
mediastinal and left lung tumors and the comprehensive efficacy
evaluation was partial response (PR) (figures 1c1,c2,c3). Four cycles of
Durvalumab maintenance immunotherapy were then administered from June to
September 2020. However, a new lesion in the right middle lobe and
enlarged left lower lobe lesion and right apical lesion were found by
chest CT scan on August 15, 2020, which means disease progressed(figures
3a1,a2,a3). Next, second-line treatment was given with chemotherapy of
etoposide plus cisplatin combined with anti-vascular therapy of
anlotinib. Two months later, chest intensive CT scan showed the mass at
low lobe of left lung and left hilus of the lung and the mediastinal
obviously progressed, and the comprehensive efficacy evaluation was
progressive disease (PD) (figures 3b1,b2,b3). The patient
cardio-pulmonary function dramatic decreased because of the
large effusion arise in the chest and
cardio bag (figures 3c1, c2), and his general condition flow down, the
ECOG 3-4. He finally died at 2020/22/15, and the overall survival time
was 10 months.
Discussion
NUT carcinoma is a rare, poor differentiated, high lethal cancer which
clinical feature as often occurred on the middle position of the body,
and happened on from children to the old, no difference at gender, hard
diagnosis, progressed fast, and no effective therapy, disaster
ending6,11-13. Pulmonary nut carcinoma is a special
kind with worse prognosis14-18. Recent years, a lots
of reports were studied. Such as Xie et all have reported an
retrospective study, they found the middle overall survival of 7
pulmonary nut carcinoma patient only were 4.1moths17.
Sholl et all retrospective reported 8 pulmonary nut carcinoma patients,
their middle overall survival time only 2.2 months15.
However, in our case, the pulmonary nut carcinoma patient got 10 months
survival through a series therapy, like chemotherapy, radiotherapy,
immunotherapy (figures 4). In our hospital, another two lung nut cancer
patient were diagnosis at march and november 2019, they are 24 years old
male, and 22 years old female, whom were both found big mass at their
chest, and were definition as local progressed stage T4N2M0 at the first
diagnosis(accessory 2,3). The male have through a unilateral lung
resection, and chemotherapy with two cycles TP (taxol and cis-platinum)
were given after the surgery, and after progressed two cycles AIM
(doxorubicin and ifosfamide) were given. Finally, he was died after 6
months later from the first diagnosis. Another female patient only
through two cycles chemotherapy with TC (taxol and carboplatin), and she
only got 2 months survival.
The therapy of nut carcinoma is a hard work, many reports showed us that
no matter the traditional chemotherapy or radiotherapy and surgery, or
the new method to antitumor, like anti-angiogenesis, immunotherapy both
could not improve the prognosis of nut
carcinoma11,12,19. The molecular mechanism of nut
carcinoma have no exactly explanation, and there have no any development
of target therapy20-23. Though some new agents
clinical trials for nut carcinoma have been conducted, but the
preliminary result is still unsatisfactory20,21.
People know nut carcinoma mostly from a lots of case report and review
of literature. Giridhar, P et.al analysis 119 nut carcinoma cases from
lots of case report, and pneumonia nut carcinoma occupy 42 cases. They
analysis the relationship of treatment and prognosis, and they found
that nut carcinoma first treat with radiotherapy with a dose exceed 50Gy
can significantly improve the overall survival of the
patients19. Also, they found that the use of pet-ct
for the first diagnosis of the disastrous carcinoma may help patient win
more time to diagnosis and treatment19. In the lung
nut cancer case we have reported previously, we can see that the patient
recur at many sites over and over again, carefully check the images of
different time, the tumor of these recur sites have been there a period
time. So, if the pet-ct were given in time, these tiny tumor were been
diagnosis as soon as possible, and then give timely and effective
therapy like radiation therapy may stop the explosive progression. In
addition, we can see from both the previously lung nut cancer case
report and this lung nut cancer case that radiation therapy can
effectively release the tumor burden at any period24.
In our previously report, radiotherapy at a dose of 20-40Gy can
effectively release tumor burden, and after 40Gy radiation, the tumor
seemingly did not recur again at a long time. In this case, the patient
only received one time radiotherapy with a dose of 56Gy, but still
recured in situ after 3 months later of the radiation, it may relative
with the discontinuous radiation. In the before case we have reported,
the radiation target volume is
involved field irradiation. But in this case, the radiation target
volume is elective nodal irradiation, and carefully comparison the
images of CT scan, we found that recurrence at the area where radiation
target volume did not covered. All in all, patient benefit more from the
radiation at the before case than this case. So, both radiation dose and
the target volume and the radiation involved time could affect the
prognosis of lung nut cancer patient. How to properly use pet-ct and
radiation at the disaster cancer is a big question which need us explore
deeply.
As far as we can see from the two cases we treated and those cases in
other doctors previous reports, the follow few points need we consider
carefully when we encounter lung nut cancer. Firstly, it is very
important to release tumor burden at the first treatment, surgery,
radiation, and chemotherapy should be consider, and the local treatment
seem more important. Secondly, radiation should be considered during the
whole disease process, so, low dose(<40Gy), accurate target
volume should be executed. For repeatedly radiation, lower dose should
be considered if the target volume is elective nodal irradiation. And
radiation should be got involved timely at every time recur. Thirdly,
because of the clinical feature of rapidly progressed, the monthly
follow-up visit is very important, and the intensive CT scan or the
pet-ct should be considered. Pet-ct could help us make a accurate target
volume. As for chemotherapy, anti-angiogenic, and immune therapy, the
effective are not sure in many cases. So, it acts according to the
circumstances on the condition of guarantee radiation.