Pulmonary tumor thrombotic microangiopathy associated with extramammary Paget's disease: An autopsy case report

Abstract

Pulmonary tumor thrombotic microangiopathy (PTTM) is histologically characterized by micro tumor cell embolism and intimal fibrocellular proliferation of pulmonary arteries or arterioles. We report a secondary case of PTTM associated with extramammary Paget's disease (EMPD). The patient was a 72‐year‐old man with exertional dyspnea. Clinical examinations found he had pulmonary hypertension and multiple osteolytic lesions of vertebra. Cytological analysis of pulmonary wedge artery sample detected malignant cells and he was dead before treatment was started. Multiple tumor embolisms (>17) were identified in pulmonary arteries or arterioles at autopsy, consistent with PTTM. Metastatic nodules were found in liver and lymph node. Furthermore, disseminated carcinomatosis of the bone marrow (DCBM) was seen. Immunostaining results pointed out that tumor cells possessed mammary gland phenotype. He had 4‐years history of EMPD in the left axilla without recurrence, and immunohistochemistry results were the same as the autopsy specimen. Thus, we diagnosed the primary site of PTTM to be EMPD. Our case highlights the usefulness of the recent proposed classification of PTTM, potential association between PTTM and DCBM, and the necessity for long‐term follow‐up in EMPD. EMPD can rarely cause PTTM to manifest as a paraneoplastic syndrome.

Trousseau Syndrome in a Case of Extramammary Paget’s Disease

“…This interaction promotes thromboembolism, immunosuppression, and metastatic spread ( 7 ), indicating that tumour-derived mucin is the cause of EMPD-associated TS. Since in situ EMPDs are often bland-looking and potentially overlooked, thrombotic complications can precede definitive diagnosis, sometimes manifesting as lethal PTTM ( 3 – 6 ). Mucin with the highest molecular weight, MUC16, is a membrane-bound, non-secretory form that may be responsible for inhibiting natural killer cell-mediated immune surveillance ( 13 ).…”

“…Based on the cancer immunoediting theory ( 1 ), in situ lesions represent a long-term cancer-immune equilibrium that keeps cancer cells within the epidermal niche, while immune escape brings about regional lymph node (LN) metastasis. However, this theory argues against the traditional view that some macule-forming, apparently non-invasive, and non-tumour-forming EMPDs progress rapidly and manifest as fatal pulmonary tumour thrombotic microangiopathy (PTTM) ( 3 – 5 ) or after years of postoperative follow-up ( 6 ). Since EMPD-associated PTTM has been reported to frequently precede diagnosis of occult EMPDs ( 3 , 4 ), precise disease recognition and elucidation of the underlying pathomechanisms of EMPD are essential for establishing better management strategies ( 2 ).…”

Pulmonary Tumor Thrombotic Microangiopathy Secondary to Extramammary Paget’s Disease: An Autopsy Case Report and Literature Review

“…Macrophages cluster around blood vessels, and signal transduction between macrophages, tumor cells, and vascular endothelial cells via osteopontin and CD44 is considered to greatly contribute to the onset of PTTM [6]. Only 2 reports of PTTM secondary to cutaneous malignancy, both of which were EMPD, have been published (Table 1) [7,8]. EMPD is a primary malignancy of the skin, and because most extramammary Paget's lesions are detected early, the prognosis is generally favorable.…”