Diagnosi differenziale di noduli polmonari: metastasi da carcinoma

Le Infezioni in Medicina, n. 1, 39-42, 2010
Casi
clinici
Case
reports
Diagnosi differenziale
di noduli polmonari: metastasi
da carcinoma della mammella
e tubercolosi polmonare
Differential diagnosis of lung nodules:
breast cancer metastases and lung tuberculosis
Mauro Endri1, Giuseppe Cartei2, Fable Zustovich2,
Francesco Saverio Serino1, Ambrogio Fassina3
1
Department of Medicine, Operative Unit of Medicine 2, Azienda Ospedaliera
Santa Maria degli Angeli, Pordenone City Hospital, Pordenone, Italy;
IOV-IRCCS, Operative Unit of Oncology 1, Padova, Italy;
3
Department of Diagnostic Medical Sciences and Special Therapies,
Section of Pathology, University of Padova, Italy
2
n INTRODUCTION
toms, physical examination, chest X Ray, total
body bone scan, abdomen and pelvis ultrasonography were negative for metastases (M0).
Thus the clinical stage was T4N1M0 (IIIB). After surgical resection, tamoxifen (20 mg daily
per os) for 5 years and periodic follow-up was
accepted by the patient.
In January 2004, a routine total body CT scan
showed multiple bilateral nodular lesions in the
lungs compatible with recurrence of breast cancer (between 5 mm and 8 mm). Markers were:
Ca125 = 23.3 U/ml (Upper Normal Range
[UNR]-35), Ca15.3 =12.8 U/ml (UNR-31.3),
CEA=1.2 ng/ml (UNR 5). Therefore exemestane (Aromasin 25 mg daily per os) was the
substitute for tamoxifen. In April 2004, a new
total body CT scan allowed a partial remission
to be evaluated (absence of new lesions, each lesion reduced >50%) and exemestane was continued. CEA was 1.2 ng/ml, Ca125 = 14.2 U/ml
and Ca15.3 = 16.1 U/ml.
In September 2004, the CT scan disclosed a generally stable disease with the exception of a
handful of nodes in the posterior segment of the
superior lobe of the right lung (largest node 2
cm), the other lesions being unchanged (Figure
1).
Due to a positive history for tuberculosis, a CT
scan guided percutaneous transthoracic fine
needle aspiration cytology (FNAC) was performed; the material was smeared onto four
slides, air dried for Giemsa and alcohol fixed
L
ung tuberculosis may occur in elderly patients with cancer, lymphoproliferative disorders and other infections like HIV [1-4]. The
presence of lung tuberculosis during chemo- or
hormone-therapy for metastatic breast cancer is
considered rare [5]. We observed an elderly patient who developed a relapse of lung tuberculosis during therapy with tamoxifen followed by
exemestane because of breast cancer.
n CASE REPORT
A 74-year-old woman presented in December
2001 with a lump in her right breast with thick
retracted overlying skin. The patient had
Karnofsky Performance Status of 100%, her
quality of life was optimal according to QLQ
EORTC 30/3, and she was a fully active international traveller. A mammography showed a
nodular lesion 4.5 cm in diameter characterized
by fimbriated borders, suggestive of breast cancer. Cytology showed cancer cells, and right
radical mastectomy and lymphoadenectomy
was performed. Histology was: G2 infiltrating
ductal carcinoma, oestrogen and progestin receptors positive, c-erb-b2 negative, Ki67 10%
positive with lymph node involvement (one
metastasis in one lymph node of second level
out of 14 total lymph nodes). Subjective symp-
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Figure 1 - CT scan showing increased nodular lesion
in the posterior segment of the superior lobe of the
right lung after specific chemotherapeutic treatment (white arrow).
Figure 3 - CT scan showing a marked decrease of tubercular lesion.
apy (rifampicin 300 mg/die and isoniazid 150
mg/die per os for six months). In May 2005, the
CT scans showed a marked reduction in the tubercular lesion while other lesions were stationary (Figure 3). The patient is currently being followed up and there are no signs of recurrence
of either tuberculosis or breast cancer progression.
n DISCUSSION
In the literature not only has association between breast cancer and tuberculosis been reported but also simultaneous concurrence of
metastatic breast cancer, Hodgkin’s disease and
tuberculosis [1-4, 7]. However, the simultaneous occurrence of breast cancer and tuberculosis is difficult to diagnose and treat, and often
tuberculosis is unrecognized and its incidence
in cancer patients remains low [8-11]. Tanaka
and coworkers conducted a retrospective review in 52 patients with breast cancer and pulmonary nodular lesions, evaluating the nature
of pulmonary lesions surgically resected [11]. In
this study 25% of cases had histological diagnoses other than breast cancer: tuberculosis was
present in only 3.8% (2/52) of patients. In our
patient, correct diagnosis would have been difficult without the CT scan and without fine needle aspirate cytology. The increase in size of a
lesion at the time of the decrease in size of most
other lesions required a FNAC, also because a
“mixed” cancer response to therapy is a wellknown phenomenon.
Figure 2 - Fine Needle Aspiration Cytology (FNAC):
granulomatous aggregates of epithelioid–like large
cells resembling giant Langerhans cells (Giemsa
x400).
for Papanicolau and one slide was immediately
stained with Diff-Quick for Rapid On Site Evaluation (ROSE) [6].
Part of the material was fixed in RNA-later solution (Ambion). Cytology revealed the presence of a necrotic background with cellular debris, granulocytes, a few lymphocytes and plasmacells with occasional granulomatous aggregates of epitheliod–like large cells resembling
giant Langerhans cells (Figure 2). A diagnosis
of tuberculosis was performed.
From the RNA later fixed material, DNA was
extracted and PCR confirmed tuberculosis diagnosis. Tuberculin skin test was positive at
that time and the patient received specific ther-
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The present case is a noteworthy example of
the possible combination in the same organ of
two distinct diseases. It is worth pointing out
the possibility of pulmonary tuberculosis when
CT scan shows marked increases of one or
more lesions even without typical tubercular
radiological features during anticancer therapies. Moreover, in recent years, fluorine-18-fluorodeoxiglucose (18 F-FDG) whole body
positron emission tomography (PET) is routinely employed in the staging and follow-up
of cancers. However, F18-FDG uptake is sometimes associated with non-cancer-related lesions. In particular, tubercular lesions are characterized by a F18-FDG uptake resulting in
false positive [12, 13]. On the other hand, breast
tuberculosis is often confused with metastases
or carcinomas, in particular in cases which are
poorly defined clinically. In the literature, case
reports of breast tuberculosis have been widely described [14-17]. In these cases, histology
remains the keystone in confirming the diagnosis [8, 9]. Thus, in differential diagnosis of
pulmonary nodular lesions, in patients with
cancer, the likely reactivation of tuberculosis
even in people without tuberculosis symptoms
should be borne in mind. In conclusion, we
should be alert to re-evaluate the incidence of
tuberculosis in cancer patients not only from
endemic regions but also in patients from industrialised countries [4, 6].
Key words: breast cancer, metastases, pulmonary nodular lesions, tuberculosis.
SUMMARY
In a follow-up a 74-year-old woman with
breast cancer (clinical stage T4N1M0 at onset,
treatment by surgical resection and tamoxifen)
presented a combination of two distinct diseases in the lung: breast cancer metastasis and
tuberculosis. A CT scan showed multiple pulmonary nodular lesions and in only one lesion
fine needle aspiration cytology (FNAC) diagnosed tuberculosis. After specific antibiotic
therapy, isoniazide and rifampin, a CT scan
highlighted disappearance of tubercular lesion.
Because occurrence of tuberculosis during
chemo or hormone therapy for metastatic
breast cancer is rare, the present case is noteworthy. Indeed, it is worth pointing out the differential diagnosis of pulmonary nodular lesions in patients with cancer and the possible
reactivation of tuberculosis even in patients
without specific symptoms, without typical tubercular radiological features.
RIASSUNTO
Durante il follow-up di una donna di 74 anni affetta da carcinoma della mammella (al momento della
diagnosi stadio secondo classificazione TNM: T4
N1 MO, trattata con terapia chirurgica e successiva terapia ormonale con tamoxifene) si osservò la
presenza di due patologie ben distinte: noduli polmonari metastatici da carcinoma mammario e tubercolosi polmonare. In particolare, la TC torace
mostrò multiple lesioni polmonari (riferibili a metastasi) ed in una sola di esse, sottoposta a FNAC, fu
posta diagnosi di TBC. Dopo la terapia antibiotica
specifica, basata su rifampicina e isoniazide, la suc-
cessiva TC torace di controllo mostrò la scomparsa
della lesione tubercolare, senza modificazioni volumetriche delle restanti lesioni. L’insorgenza di tubercolosi polmonare durante chemioterapia o terapia ormonale per il trattamento di metastasi polmonari da carcinoma mammario è piuttosto rara e pertanto riteniamo il presente caso degno di nota. Infatti, potrebbe essere utile porre diagnosi differenziale tra noduli polmonari in pazienti con cancro e
possibile riattivazione di focolai tubercolari, soprattutto in quei soggetti senza sintomi specifici e senza segni radiografici tipici.
n REFERENCES
[2] Ibrahim E.M., Uwaydah A., Mulhim F.A.,
Ibrahim A.M., el-Hassan A.Y. Tuberculosis in patients with malignant disease. Indian J. Cancer. 26, 5357, 1989.
[3] Avninder S., Saxena S. Infiltrating ductal carcino-
[1] Kaplan M.H., Armstrong D., Rosen P. Tuberculosis complicating neoplastic disease: a review of 201
cases. Cancer 33, 850-858, 1974.
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2010
pulmonary tuberculosis in malignancy. Tumori 88, 3,
251-254, 2002.
[11] Tanaka F., Li M., Hanaoka N., et al. Surgery for
pulmonary nodules in breast cancer patients. Ann.
Thorac. Surg. 79, 1711-1715, 2005.
[12] Ataergin S., Arslan N., Ozet A., Ozguven M.A.
Abnormal FDG uptake on 18F-fluorodeoxyglucose
positron emission tomography in patients with cancer diagnosis: case reports of tuberculous lymphadenitis. Intern. Med. 48, 2, 115-119, 2009.
[13] Das C.J., Kumar R., Balakrishnan V.B., Chlawla
M., Malhotra A. Disseminated tuberculosis masquerading as metastatic breast carcinoma on PETCT. Clin. Nucl. Med. 33, 5, 359-361, 2008.
[14] Morino G.F., Rizzardi G., Gobbi F., Baldan M.
Breast tuberculosis mimicking other diseases. Trop.
Doct. 37, 3, 177-178, 2007.
[15] Maroulis I., Spyropoulos C., Zolota V., Tzorakoleftherkis E. Mammary tuberculosis mimicking
breast cancer: a case report. J. Med. Case Reports 34, 12, 2008.
[16] Bianco S.R., Gurgel R.L., Taveres A. Radiological
aspects of primary tuberculosis in the breast: a case
report and review of the literature. Rev. Soc. Bras.
Med. Trop. 42, 2, 203-205, 2009.
[17] Ochoa Aguilar M.A., Ortiz Martinez J.D. Tuberculosis of the breast. A case report. Ginecol. Obstet.
Mex. 77, 6, 282-286, 2009.
ma of the breast, metastatic to axillary lymph nodes
harboring primary tuberculosis lymphadenitis. Patol.
Oncol. Res. 12, 3, 188- 189, 2006.
[4] Wani B.N., Jajoo S.N. Ipsilateral axillary tubercular lymphoadeopathy, contralateral osseous tuberculosis in a case of ductal carcinoma of breast. Indian J.
Cancer. 45, 4, 182-184, 2008.
[5] Ito K., Fujimori M., Hama Y., et al. Pulmonary tuberculosis in a patient receiving intensive
chemotherapy for metastatic breast cancer. Breast J.
11, 1, 87-88, 2005.
[6] Santambrogio L., Nosotti M., Bellaviti N., et al. CT
guided fine needle aspiration cytology of solitary
pulmonary nodules: a prospective, randomized
study of immediate cytologic evaluation. Chest 112,
2, 423-425, 1997.
[7] Broughton A., Galant C., Haianaut P. Simultaneous occurrence of metastatic breast cancer,
Hodgkin’s disease and tuberculous kymphadenitis
in homolateral axillary lymphnodes: a case report.
Acta Clin. Belg. 63, 6, 391-393, 2008.
[8] Alzaraa A., Dalal N. Coexistence of carcinoma
and tuberculosis in one breast. World J. Surg. Oncol.
29, 4-6, 2008.
[9] Madhusudhan K.S., Gamanagatti S. Primary
breast tuberculosis masquerading as carcinoma. Singapore Med. J. 49, 1, e3-e5, 2008.
[10] Karnak D., Kaykan O., Beder S. Reactivation of
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2010