Diagnostic Puzzlers: An elderly man with lung and shoulder masses

January 1, 2006
The Journal of Respiratory Diseases Vol 6 No 1, Volume 6, Issue 1

An 85-year-old man with a history of hypertension, coronary artery disease, and diabetes mellitus presented with syncope. He had fallen down a flight of stairs and now complained of left shoulder pain

An 85-year-old man with a history of hypertension, coronary artery disease, and diabetes mellitus presented with syncope. He had fallen down a flight of stairs and now complained of left shoulder pain.

The patient denied chest pain, shortness of breath, and cough. He was an ex-smoker. His medical history was notable for a 12-lb weight loss over the previous 2 months, coronary artery bypass graft surgery 15 years ago, and the placement of a permanent pacemaker 6 weeks before presentation. Recently, he was found to have a left upper lobe lung nodule, which was in the process of being evaluated.

On examination, his heart rate was 72 beats per minute, respiration rate was 18 breaths per minute, and oxygen saturation on room air was 98%. His chest was clear to auscultation, with no dullness to percussion. There was pain on palpation and on passive motion of the left shoulder.

A CT scan of the chest revealed a 4-cm spiculated mass in the right upper lobe and a mass in the left shoulder. There was lytic destruction of the bone adjacent to the mass. The patient underwent a CT-guided biopsy of the left shoulder mass (Figure 1). Low-power and high-power views of the biopsy specimen are shown below (Figures 2A and 2B, respectively).

A whole-body positron emission tomographic scan revealed increased uptake correlating with the mass in the right upper lobe of the lung and erosion of the left shoulder mass into the scapula. A smaller area of uptake was seen in the right shoulder. Hypermetabolic areas were also seen in lymph nodes of the central right hilum and precarinal regions. A small focus was seen in the right lobe of the liver. No abnormalities were evident in the left lung or in the abdominal, pelvic, and inguinal regions.

What is the likely diagnosis? How would you proceed?

An elderly man with lung and shoulder masses: The low-power view of the biopsy specimen from the left shoulder mass shows some cells with plasmacytoid morphology and several others with a single, large vacuole and indented nuclei, referred to as signet-ring cells (Figure 2A). The high-power view shows a 3-dimensional cluster of adenocarcinoma cells surrounded by single adenocarcinoma cells that reveal plasmacytoid and signet-ring morphology (Figure 2B). Note that each of the signet-ring cells contains a single, large cytoplasmic mucin vacuole and an indented nucleus (Figure 3). Each of the plasmacytoid cells has an enlarged eccentric nucleus with a large nucleolus and finely vacuolated cytoplasm.

The diagnosis was signet-ring cell adenocarcinoma of the lung.


Signet-ring cell adenocarcinoma is a relatively rare variant of adenocarcinoma. Most signet-ring cell adenocarcinomas in the lung are metastatic; they typically arise from cancers in the GI tract, breast, prostate, or urinary bladder. Less commonly, these adenocarcinomas occur as primary tumors in the lung.

Kish and associates1 were among the first to report signet-ring cell adenocarcinoma in the lung, in 1989. In 1999, a revised classification of lung and pleural tumors was developed jointly by the World Health Organization and the International Association for the Study of Lung Cancer, at which time signet-ring cell adenocarcinoma was recognized as a histologic subtype of adenocarcinoma.2

Clinically, signet-ring cell adenocarcinoma manifests with signs and symptoms similar to those of any other type of lung tumor. Patients may be asymptomatic or may present with cough, hemoptysis, dyspnea, chest pain, postobstructive pneumonia, or lung abscess. Other clinical manifestations occur based on regional or distant spread of the tumor.

Histologically, a signet-ring cell is defined as a cell ringlike in shape that contains a crescent-shaped nucleus displaced to one side by large mucin droplets. Signet-ring cells are usually seen as part of an adenocarcinoma or, less commonly, an adenosquamous cell carcinoma. A pure signet-ring cell tumor is very rare. The histologic distinction between primary pulmonary signet-ring cell adenocarcinoma and metastatic signet-ring cell adenocarcinoma is very difficult to ascertain, given the similarity in morphologic appearance. Because of this similarity, researchers have studied many immunohistochemical markers.

Among these markers, thyroid transcription factor-1 (TTF-1) expression is highly specific for primary pulmonary signet-ring cell adenocarcinoma; thus, TTF-1 positivity favors a primary lung tumor.3 In contrast, mucin-producing primary pulmonary adenocarcinoma appears to be TTF-1-negative. Cytokeratin 20 negativity may also support the diagnosis of a primary lung tumor.4

Overall, the prognosis for patients with signet-ring cell adenocarcinoma is poor. Tsuta and colleagues5 found an association between clinical course and the percentage of signet-ring cells in the tumor. They concluded that in patients with tumors that had a signet-ring cell component of approximately 50%, there was a significantly higher rate of lymph node metastases and blood and lymph vessel invasion; the overall 5-year survival rate was appreciably lower for these patients than for patients with non-signet-ring cell tumors.

Outcome in this case

The patient was given palliative radiation therapy for the shoulder mass. He died of complications of the malignancy about 1 month later.

Case and photographs courtesy of Subani Chandra, MD, Paul Strachan, MD, Nora Morgenstern, MD, Leonard Rossoff, MD, and Arunabh Talwar, MD, of Long Island Jewish Medical Center, New Hyde Park, New York, and North Shore University Hospital, Manhasset, New York.



1. Kish JK, Ro JY, Ayala AG, McMurtrey MJ. Primary mucinous adenocarcinoma of the lung with signet-ring cells: a histochemical comparison with signet-ring cell carcinomas of other sites.

Hum Pathol.

2. Brambilla E, Travis WD, Colby TV, et al. The new World Health Organization classification of lung tumours.

Eur Respir J.

3. Merchant SH, Amin MB, Tamboli P, et al. Primary signet-ring cell carcinoma of lung: immunohistochemical study and comparison with non-pulmonary signet-ring cell carcinomas.

Am J Surg Pathol.

4. Castro CY, Moran CA, Flieder DG, Suster S. Primary signet ring cell adenocarcinomas of the lung: a clinicopathological study of 15 cases.


5. Tsuta K, Ishii G, Yoh K, et al. Primary lung carcinoma with signet-ring cell carcinoma components: clinicopathological analysis of 39 cases.

Am J Surg Pathol.