ROTOLO, NICOLADOMINIONI, LORENZODe Monte LConti VLa Rosa SIMPERATORI, ANDREA SELENITOmostra contributor esterni nascondi contributor esterni 

CASE R E PORT

Metastasis at a tracheostomy site as the presenting sign of late recurrent breast cancer

Nicola Rotolo, MD,

Lorenzo Dominioni, MD,

Lavinia De Monte, MD,

Valentina Conti, MD,

Stefano La Rosa, MD,

Andrea Imperatori, MD

1

Center for Thoracic Surgery, University of Insubria, Ospedale di Circolo, Varese, Italy,

Department of Pathology, University of Insubria, Ospedale di Circolo, Varese, Italy.

Accepted 30 November 2012

Published online 18 March 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23234

ABSTRACT: Background. Metastasis in a tracheostomy site occurs rarely, usually from head and neck primary tumors. Breast cancer relapse to a tracheostomy has not been described to date.

Methods and Results. A 71-year-old women presented with symptoms typical of central airway obstruction, 10 years after mastectomy for breast cancer. Fifteen months before admission, when cancer follow- up was negative, she also had surgery for cerebral aneurysm and a tracheostomy. On admission, CT showed a solid mass infiltrating the tracheostomy tract and projecting into the airway. Tracheal obstruction palliation was achieved by laser resection of the

endotracheal growth and stenting. Histology documented breast cancer metastasis.

Conclusions. Tracheostomy site metastasis was the presenting sign of late-onset relapse of breast cancer. This case supports the concept of surgery-driven interruption of micrometastatic cancer dormancy, in that the initial recurrence developed in a tracheostomy that was surgically created several years after resection of the primary tumor. V

2013 Wiley Periodicals, Inc. Head Neck 35: E359–E362, 2013

KEY WORDS: tracheostomy, metastasis, breast cancer, dormancy, laser resection

INTRODUCTION

Relapse of head and neck cancer at a tracheostomy site is unusual but well documented.

The mechanisms that have been proposed to explain such recurrence include intraoperative implantation from tumor-contaminated instruments, and growth at the stoma site of cancer cells disseminated by the lymphatic or hematogenous route.

Moreover, it has been postulated that local inflammation and tissue trauma around the stoma may provide a favorable microenvironment for the growth of dormant metastases.

Patients with breast cancer, the most frequent malignant tumor among females, are at risk of developing metastases ubiquitously during their entire lifetime.

To our knowledge, however, metastasis of cancer of the breast to a tracheostomy has not been described previously.

CASE REPORT

A 71-year-old woman was admitted to our hospital as an emergency for acute respiratory failure on January 6, 2010. The patient reported nonproductive cough for several weeks, hemoptysis and progressive dyspnea in the previous days. She had signs of central airway obstruction with tirage and cyanosis, and her peripheral blood O

saturation was 86% in room air. Inspection of her neck revealed a tracheostomy scar with reddened skin, under

which a 3-cm solid mass extending deeply in the neck was palpable. The patient had a history of cancer of the right breast, diagnosed in 2000. This lesion was invasive ductal carcinoma positive for progesterone and estrogen receptors and negative for human epidermal growth factor receptor 2. The tumor was 25 mm in diameter, stage pT2, pN1b, G2. The serum level of CA 15-3 was 38.6 U/mL (normal range, 0–30 U/mL). Treatment was effected with radical mastectomy, followed by chemotherapy (6 cycles of cyclophosphamide, methotrexate, and fluorouracil), radiotherapy (50 Gy), and 5-year tamoxifen. Semiannual follow-up was then carried out regularly, with negative findings. In September 2008 the patient developed a rup- tured cerebral aneurysm that required surgical clipping and cerebral decompression. She also needed a tracheos- tomy that was made without encountering any tissue abnormalities in the neck. Recovery after the neurosurgi- cal procedure was satisfactory, with minor neurologic def- icit, and the tracheostomy cannula was removed after 8 months, followed by spontaneous closure of the stoma.

The patient was subsequently lost to follow-up.

On admission, approximately 15 months after the cere- brovascular accident, staging with showed a 3-  4-cm solid growth in the soft tissues of the neck above the ster- nal notch that infiltrated the tracheotomy tract. This growth projected into the tracheal lumen 3 cm below the vocal cords, severely obstructing the airway (5 mm free space) (Figures 1A–C). Moreover, CT demonstrated a sin- gle 1.8-cm nodule in the right upper lung lobe, suspicious for malignancy (Figure 2). There was no other evidence of metastases elsewhere. Tracheo-bronchoscopy confirmed approximately 90% obstruction of the airway, caused by a 2.5-cm solid mass growing from the second and third

*Corresponding author: L. Dominioni, Center for Thoracic Surgery, University of Insubria, Ospedale di Circolo, Varese, Italy.

E-mail: lorenzo.dominioni@uninsubria.it The authors declared no conflict of interest.

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tracheal rings into the lumen (Figure 3A). The bulk of the endotracheal growth was removed with diode laser through the rigid bronchoscope, and clearance of the air- way was obtained (Figure 3B). Histology of the excised endotracheal growth revealed invasive ductal carcinoma of the breast with positivity for progesterone and estrogen receptors (Figures 4A and 4B), with an immunohisto- chemical pattern mirroring that of the primary cancer resected 10 years earlier (Figures 4B and 4C). Needle bi- opsy of the right lung nodule also showed the same im- munohistochemical features of breast cancer metastasis.

The serum CA 15-3 level was normal (20.8 U/mL). After laser ablation of the endotracheal mass, a silicone 12-mm tracheal stent was positioned (Dumon; Novatech, La Cio- tat, France). Therapy with aromatase inhibitor (Exemes- tane) was instituted, but the patient did not respond and died with disseminated metastases on June 26, 2010, approximately 6 months after diagnosis of breast cancer relapse.

DISCUSSION

Breast cancer metastases frequently localize in the lower respiratory tract,

whereas tracheal involvement is uncommon and usually characterized by compression/

infiltration from adjacent pulmonary or paratracheal lymph node metastases.

Direct metastases of breast can- cer to the trachea are exceedingly rare; a search of the lit- erature revealed that only 3 such cases have been reported.

The rarity of the case presented here may be explained by the scarce propensity of breast cancer to relapse at tracheal level, in addition to the fact that patients with exceptional cases of breast cancer need a tracheostomy. An increased level of CA 15-3 is often associated with metastatic breast carcinoma,

but in our patient the serum level of this marker was normal when recurrence was diagnosed. Evidence of endotracheal me- tastasis of breast cancer at the tracheostomy was the first indication of relapsed disease, 10 years after resection of the primary tumor. Notably, the latter was estrogen

receptor–positive, a feature associated with greater hazard of recurrence from years 5 to 12.

Breast cancer relapse more than 10 years after apparently radical resection of the primary lesion is a well-documented event.

A possible mechanism for late recurrence of breast cancer is the reactivation of fully malignant tumor cells seeded before or at the time of primary tumor resection that remained "dormant" for many years.

In addition, it has been shown that wounds are a favorable microenviron- ment for tumor growth and that local tissue trauma and inflammation contribute to tumorigenesis and malignant disease progression.

It is noteworthy that in our patient the tracheostomy was made without encountering any abnormalities in the anterior neck tissues, thus ruling out a preexisting clinically detectable relapse. Therefore, we hypothesize that the surgical procedures performed in September 2008 (clipping of aneurysm and tracheostomy) facilitated the outgrowth of otherwise dormant circulating cancer cells at the tracheostomy, a site characterized by inflammation and granulation caused by the tracheal

FIGURE 1. CT axial (A) and coronal (B) views showing a solid mass (arrows) infiltrating the soft tissues of the anterior aspect of the neck, and the trachea. CT sagittal view (C) shows the neoplastic growth that extends from the cutaneous scar of the tracheostomy to the tracheal wall and invades the airway. The latter is subtotally obstructed by the solid growth (arrows).

FIGURE 2. CT scan showing a 1.8-cm peripheral nodule with spiculated margins in the right upper lobe of the lung.

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cannula. Fifteen months elapsed from tracheostomy placement and symptomatic diagnosis of the 3-  4-cm recurrent growth at the stoma site, a time interval that may seem exceedingly short for such a large recurrence to develop. However, in agreement with the short volume

doubling time of breast cancer recurrences, reported to range between 25 and 51 days,

we estimated that a micrometastasis growing up to 4 cm in diameter in 15 months would have a volume doubling time of about 30 days. Interestingly, a review of percutaneous endoscopic

FIGURE 3. Endoscopic view of neoplastic growth bulging into the airway from the anterior aspect of the tracheal wall (A), at the second to third ring level (arrow). Clearance of the airway was achieved after removal of the neoplastic growth with the diode laser. Tip of laser probe indicated by arrows (B). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIGURE 4. Histological features of the endotracheal growth showing metastasis of breast carcinoma (A, B). Proliferation in the subepithelial layer of tumor cells with eosinophilic cytoplasm, and nuclei with evident nucleoli arranged in cords and trabeculae with zonal glandular differentiation (A, hematoxylin-eosin stain, original magnification 200). Tumor cells express estrogen receptors (ER) at the nuclear level (B, original magnification 400). These morphologic and immunohistochemical features largely overlap those of the primary breast carcinoma resected 10 years before, shown in (C) (hematoxylin-eosin stain, original magnification 400) and in D (ER expression, original magnification 400). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

TRACHEOSTOMY SITE METASTASIS OF BREAST CANCER

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gastrostomy (PEG)–associated metastases from head and neck tumors reported that stomal recurrence became clini- cally evident at a mean of 8 months (range, 2–24 months) after PEG placement.

In our patient, persistent cough was long misinterpreted as chronic bronchitis, and the diagnosis of tracheal metas- tasis was delayed until the occurrence of acute respiratory failure with tirage, when the airway lumen was nearly occluded. When the disease is multimetastatic, as in our case, treatment is symptom palliation, associated with chemotherapy and hormone therapy, if feasible.

Laser resection of endotracheal metastasis and stent placement are recommended to obtain tracheal canalization when acute respiratory failure occurs. These endoscopic proce- dures may improve the quality of life and prolong sur- vival for a brief period. Regardless of the primary tumor histology and the type of treatment, however, the pres- ence of tracheal metastasis from distant malignancies points to widespread disease and dismal prognosis, with survival ranging from a few months to 2 years.

One of the 3 published cases of breast cancer recurrence to the trachea survived 8 months, and no information is available on the survival period of the other 2.

CONCLUSIONS

Late-onset metastasis of breast cancer is often associated with disseminated disease. In the case presented, tracheal obstruction was the initial sign of late recurrence in a tra- cheostomy, a distant site of breast cancer relapse that has not been described to date. Moreover, this case supports the concept of surgery-driven interruption of circulating breast cancer cell dormancy, given that the initial and larg- est recurrence developed in a tracheostomy that was surgi- cally created 8.5 years after removal of the primary tumor.

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