Diagnostic Puzzler: What caused this woman's 'myoma'?

DIAGNOSTIC PUZZLER What caused this woman's 'myoma'? By Antoun Khabbaz, MD, Christopher V. Lutman, MD, and Andrew Berchuck, MD KP, a 37-year-old woman, presented to the emergency room with heavy vaginal bleeding that had lasted 9 days. Physical exam revealed orthostatic hypotension and an 18-week uterus. During hysterectomy, a broad ligament nodule was removed. Dr. Khabbaz presents details of the case When KP presented to the ER, her hematocrit was 20% and chest x-ray and ECG findings were normal. Endometrial biopsy revealed a benign secretory endometrium and her Pap smear was negative for dysplasia and malignancy. Ultrasonography of the pelvis revealed an enlarged uterus with multiple myomas and a 3-cm simple cyst of the left ovary. We transfused KP with 2 units of packed red blood cells and gave her an injection of leuprolide acetate. Two months later, she decided to have a hysterectomy with ovary preservation. During the surgeryan uncomplicated abdominal hysterectomywe found a 3 x 3-cm right broad ligament nodule, which we thought was a myoma (Figure 1). A postoperative surprise. KP's postoperative course was complicated by new-onset severe hypertension, which we controlled with quinapril hydrochloride, clonidine, metoprolol tartrate, and nitropaste. Our cardiac work-up ruled out myocardial infarction. On postoperative day 1, the pathologist called with unexpected results. The "myoma" was actually a malignant neoplasm "suspicious for metastatic carcinoma in ovarian tissue" and the pathologist suggested that the primary source was gastrointestinal, neuroendocrine, or breast! KP's cervix showed widespread severe dysplasia. HIV testing was negative. No suspicious lesions were seen on mammography. Abdominal and pelvic CT revealed bulky bilateral pelvic lymphadenopathy with no evidence of abdominal disease. A postoperative chest x-ray taken because of fever showed a large right apical mass. Chest CT confirmed a right apical pleural-based mass with rib destruction and right suprahilar and paratracheal adenopathy. The primary cancer was in the lung. The final diagnosis: Pancoast tumor of the lung. The oncology team subsequently diagnosed nonresectable Pancoast tumor of the lung and recommended outpatient follow-up. CT-guided fine-needle aspiration of the mass showed non-small cell lung cancer (NSCLC) (Figures 2 and 3). The patient was offered palliative chemotherapy. Drs. Lutman and Berchuck comment on the case Approximately 6% to 8% of ovarian cancers that surgeons encounter when exploring women who have pelvic or abdominal masses are metastases to the ovary. Cancers of the genital tractsuch as the endometrium, fallopian tube, and cervixcan metastasize to the ovary. The colon and the breast are the most common extragenital sites of primary cancer metastatic to the ovary. Other primary sites include the stomach, pancreas, skin (that is, melanoma), kidney, and lung. The classic Krukenberg tumor originally described ovarian tumors arising from metastases of gastric origin, but the signet ring cells that are pathognomonic for these tumors also are present even if the primary cancer arises in the breast, colon, or pancreas. Grossly, Krukenberg tumors form a solid, often uniform mass. Gelatinous necrosis and hemorrhage often are found on sectioning. Because gastric adenocarcinomas are on the decline in the US, you are more likely to see a colon cancer that has spread to the ovary than to see Krukenberg tumors. Microscopically, these lesions are characterized by large acini similar to those of primary colon cancer. On gross examination, the tumors are usually large, partially cystic lesions with areas of hemorrhage and necrosis. Pathways of metastasis. Cancer can spread to the ovary by four possible mechanisms: (1) direct extension; (2) surface papillation; (3) lymphatic channels; and (4) hematogenous spread. The most common is lymphatic spread. Breast cancers found in the ovary are often limited to the medullary lymphatics. Colon cancer can spread via direct extension. Exploring a woman with a pelvic mass sometimes leads to the difficult task (for surgeon and pathologist) of defining a primary site for adenocarcinoma when the colon and adnexa are enmeshed into one, malignant mass. To date, no investigator has convincingly described the pathways of metastasis from the stomach or pancreas to the ovaries. Lymphatics that drain the upper gastrointestinal tract and the ovarian lymphatics both ultimately connect to the lumbar lymphatics. This may be the route of spread in these cases. Perspective on Pancoast tumor. The case described herelung cancer metastatic to the ovaryis extremely unusual: fewer than 20 cases exist in the literature. After resection of the pelvic mass and an unexpected pathologic diagnosis, a thorough search for the primary cancer led to the diagnosis of Pancoast tumor. Pancoast tumor is an anatomic term used to describe a neoplasm of pulmonary origin located at the apical pleuropulmonary groove (the superior sulcus). These tumors usually spread by direct extension to involve the brachial plexus, intercostal nerves, stellate ganglion, adjacent ribs, and vertebrae. In the US, fewer than 5% of all primary lung cancers fit the anatomic definition of Pancoast tumor. Ninety-five percent of Pancoast tumors are NSCLCs. Squamous cell carcinomas, adenocarcinomas, and large cell carcinomas are the most frequent histologic types seen. Fewer than 5% of Pancoast tumors are small cell carcinomas. Patients with Pancoast tumor typically present with shoulder pain as a result of tumor extension into the brachial plexus, parietal pleura, endothoracic fascia, vertebral bodies, or the first three ribs. Weakness, atrophy, and paresthesias of the hand, arm, and forearm are common. In up to 25% of cases, invasion of the cancer into the intervertebral foramina leads to compression of the spinal cord and paraplegia. Horner's syndrome, the classic triad that causes sinking in of the eyeball, prolapse of the upper eyelid, and absence of sweating, occurs in up to 50% of patients. This is caused by invasion of the paravertebral sympathetics and stellate ganglion. Less common manifestations include phrenic or recurrent laryngeal nerve involvement and superior vena cava syndrome. Pancoast tumor can also be associated with systemic paraneoplastic syndromes: inappropriate secretion of antidiuretic hormone, ectopic production of adrenal corticotropin hormone (ACTH), hypercalcemia, hypercoagulability and thrombosis, digital clubbing, gynecomastia, and CNS abnormalities unrelated to metastases. The patient in the case presented here did have unexplained severe postoperative hypertension. If that condition was related to the lung cancer, then it most likely was secondary to ectopic production of ACTH by the cancer. Staging of Pancoast tumor involves the tumor, node, and metastasis (TNM) classification scheme, where T indicates the site and size of the primary tumor, N indicates the extent of lymph node involvement, and M indicates the presence or absence of distant metastasis. M0 indicates no distant metastases, whereas M1 indicates the presence of distant metastases. Metastatic tumor in the ipsilateral lobe of the lung not involved by primary disease or metastases to other organ systems is considered M1. This patient presented with an ovarian metastasis, making her disease classification M1. The primary treatment for a patient with Pancoast tumor is radiation. Tumors considered operable can be resected and staged after radiation therapy. Tumors considered inoperable secondary to advanced local extension are treated with radiation therapy alone. Doses of 6,000 cGy or greater are used to control local tumor growth and to palliate the symptoms caused by tumor invasion into adjacent structures. Patients with distant metastases can be offered palliative chemotherapy as well as local radiation therapy. Overall, the 5-year survival rate for patients with Pancoast tumor and distant metastases is less than 10%. A final observation. What's interesting about this particular case is the fact that the patient had none of the dramatic local symptoms typically associated with Pancoast tumor, even though she did have bony involvement in her chest. This woman's cancer was discovered accidentally after exploration and hysterectomy for uterine fibroids. That was likely the case because of early hematogenous spread of the lung cancer to her pelvis before local symptoms became apparent. (Recall that the tumor was not visible on the chest x-ray taken in the ER, but had grown rapidly enough to be evident on the patient's postoperative x-ray.) Absent the uterine fibroids that triggered the discovery of the metastasis in this woman's pelvis, it is likely that onset of local symptoms eventually would have led to discovery of her lung cancer. REFERENCES 1. DiSaia PJ, Creasman WT: Clinical Gynecologic Oncology. 6th ed. St. Louis, Mo: C.V. Mosby Co; 2002. 2. Nelson BE, Carcangiu ML, Chambers JT. Intraabdominal hemorrhage with pulmonary large cell carcinoma metastatic to the ovary. Gynecol Oncol. 1992;47:377-381. 3. Mazur MT, Hsueh S, Gersell DJ. Metastases to the female genital tract. Analysis of 325 cases. Cancer. 1984;53:1978-1984. 4. Arcasoy SM, Jett JR. Superior pulmonary sulcus tumors and Pancoast's syndrome, N Engl J Med. 1997;337:1370-1376. 5. Ginsberg RJ, Payne DG, Shamju FS. Superior sulcus tumors. In: Aisner J, ed. Comprehensive Textbook of Thoracic Oncology. Philadelphia, Pa: Williams & Wilkins Co; 1996:375-387. Dr. Khabbaz is an Obstetrician Gynecologist in practice at Harlan Appalachian Regional Healthcare Hospital, Harlan, Ky. He encountered the case described here as a resident at Stony Brook University Hospital, State University of New York, Stony Brook, N.Y. Dr. Lutman is a Gynecologic Oncology Fellow, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, N.C. Dr. Berchuck is F. Bayard Carter Distinguished Professor of Obstetrics and Gynecology, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, N.C. Photos courtesy of Gary Main, Stony Brook University Hospital, Stony Brook, N.Y. Antoun Khabbaz, Andrew Berchuck, Christopher Lutman. Diagnostic Puzzler: What caused this woman's 'myoma'? Contemporary Ob/Gyn Nov. 1, 2003;48:108-112.