Case 2 Dr. Leslie Clinical History

A 37 year old woman was gardening in her back yard when she suddenly felt a “pop” in her posterior chest, followed by pain and shortness of breath. A CT scan revealed a pneumothorax and multiple cysts.

Estrogen Receptor

CD10 Causes of Pneumothorax

Primary (unknown etiology) Secondary Trauma Traumatic Esophageal rupture Iatrogenic – lung biopsy, pleural biopsy or fine-needle biopsy; mechanical ventilation; thoracotomy; placement of subclavian vein catheter, chemotherapy Primary lung diseases Asthma Cystic fibrosis Usual interstitial pneumonia Pulmonary infarction Hypersensitivity pneumonitis Infections – necrotizing cavitary lesions (tuberculosis, coccidioidomycosis), Pneumocystis jirovecii pneumonia, HIV infection Emphysema Distal acinar Bullae (emphysematous cystic spaces larger than 1 cm) Secondary to other causes such as alpha-1-antitrypsin deficiency Pleuropulmonary blastoma Malignant (particularly necrotizing cavitary) tumors – primary and metastatic Pleural conditions Pleural blebs Malignant (particularly necrotizing cavitary) tumors – mesothelioma and metastases Systemic conditions that involve lung and pleura Endometriosis (catamenial pneumothorax) Lymphangioleiomyomatosis Langerhans cell histiocytosis Connective tissue diseases – Ehlers Danlos syndrome, Marfan syndrome Sarcoidosis Birt Hogg Dube syndrome Lung Tumors that may Cystic

Squamous cell carcinoma Alveolar adenoma Lymphangioleiomyomatosis (LAM) Benign metastasizing leiomyoma Endometrial stromal sarcoma Metastatic dermatofibrosarcoma protuberans (DFSP) Benign metastasizing dermatofibroma (!) Metastatic gastrointestinal stromal tumor (GIST) Infantile pleuropulmonary blastoma

Endometrial Stromal Sarcoma

• Distant metastasis of ESS is rare and lung is the most common site of spread, sometimes occurring many years after the original tumor has been treated.

• In the series of 16 patients presented by Aubrey et al in 2002 (1), solid lung nodules were most commonly identified. Three (3) patients presented with cystic lung lesions radiologically and in two of these patients cysts predominated.

• Nearly all of the cases demonstrated areas that appeared biphasic, where tumor cells were seen to grow into lung interstitium producing microscopic cysts lined by TTF-1 positive non-neoplastic respiratory epithelium. Immunohistochemical Results (Aubry et al)

Stains Positive cases (%) Focal Diffuse ER 13/13 (100) 0 13

PR 14/14 (100) 0 14

Vimentin 13/14 (93) 0 13

Smooth muscle actin 8/14 (57) 5 3

Desmin 7/14 (50) 4 3

Keratin AE1/AE3 6/13 (46) 3 3

Inhibin 1/14 (1) 1 0

CAM5.2 1/14 (1) 1 0

Chromogranin 1/14 (1) 1 0

HMB45 1/14 (1) 1 0

CD34 1/14 (1) 1 0

ER, estrogen receptor nuclear protein; PR, progesterone receptor nuclear protein. Endometrial Stromal Sarcoma

• 15 patients in the series were alive 3 months to 13 years after the first lung metastasis was discovered. Recurrent lung metastasis was identified in 4 patients.

A word about molecular genetic findings in Synovial Sarcoma • In over 90% of cases, chromosomal translocation t(X:18)(p11.2;q11.2) (i.e., fusion of SYT gene on ch. 18 with either SSX1 (2/3 of cases) or SSX2 (1/3 of cases) on ch. X). • ? Correlation between biphasic tumors and SYT- SSX1 fusion type, monophasic fibrous tumors and SYT-SSX2 fusion type. • Longer metastasis-free survival with localized tumors having SSX2 fusion type. • SYT-SSX1 fusion associated with higher Ki-67 index and mitoses. References

1. Aubrey MC, Myers JL, Colby, TV, Leslie KO, Tazelaar HT: Endometrial stromal sarcoma metastatic to the lung. A detailed analysis of 16 patients. Am J Surg Pathol 26(4): 440-449, 2002 Questions