Contributed by Alcidea da C. Rosa, MD; Marcus Vinicius Pinto, MD; Victor Hugo R. Marussi MD; Nathalie H. Silva Canedo, MD, PhD; Luiz Felipe R. Vasconcellos, MD, MSc.
DIAGNOSIS
Leptomeningeal amelanotic melanomatosis and brain metastases from gastric melanoma.
DISCUSSION
Cancer in the defunctionalized distal stomach after gastric bypass for morbid obesity was first reported in 1991, 25 years after the procedure was introduced for this indication. As opposed to Billroth II gastrectomy for peptic ulcer disease, the distal stomach has been bypassed in this operation and this segment may be subject to different influences on oncogenesis. In the region of the anastomosis, duodenogastric reflux is responsible for the development of premalignant lesions involving adenocystic proliferation. This lesion expresses the gastric phenotype, and develops into diffuse type carcinoma. It causes different histological changes in the gastric stump such as intestinal metaplasia, dysplasia and adenoma (5).
The symptoms of gastric stump carcinoma are often neglected by the patients, because partial gastrectomy leads to gastrointestinal symptoms and some patients misinterpret such symptoms as a recurrence of their original ulcer disease. The initial symptoms reported by most patients were weight loss and unspecific abdominal complaints (7).
This case described an unusual clinical course of diffuse malignant leptomeningeal melanomatosis that began as acute ascending paraparesis, with no identified primary lesion, at first. Leptomeninges involvement produces symptoms and signs resulting from either obstruction of the cerebrospinal fluid (CSF) flow or direct infiltration of nerves producing neurological deficits (3). Case reports in the literature show the commonest presentations to be cranial nerve palsies (III, IV, VI and VII being involved most frequently), cerebral disturbance, spinal nerve root involvement (often associated with debilitating radiculitis) and gait disturbance (2).
Leptomeningeal carcinomatosis (LC) occurs in between 5 and 8% of patients with cancer. Common solid tumors associated with LC include, in order of frequency: breast, lung and malignant melanoma (MM). MM represents 6-18% of LC cases while 23% of MM cases will ultimately result in LC. Lumbar puncture (LP) to obtain CSF samples for cytological and biochemical assessment is the most useful test in suspected cases of LC (6). Clinicians should be aware that 50% of patients with LC have a negative cytology result on the first LP, as occurred in this case. This percentage drops to 15% after 3 high volume LPs. Modestly elevated protein, mild lymphocytic pleocytosis and reduced glucose levels are found in the majority of LC cases. In this report it is hypothesized that the extraordinarily high CSF protein levels and unusual macroscopic consistency were due to obstructed CSF flow around the patient's heavily infiltrated cauda equina (6). The primary site was only possible to define after autopsy that diagnosed an extra-cutaneous melanoma, on the stomach, with the same profile of metastasis.
Primary gastric melanoma is very rare. Most of the melanomas found in the stomach are metastases from cutaneous sources (3). Since normal stomach epithelium lacks melanocytes, the cell of origin remains obscure. Ectopic migration of melanocyte precursors or differentiation of the APUD cells (amine precursor uptake and decarboxylation cells) to melanocytes has been suggested as a possible mechanism of the development of melanoma (7). Criteria for the diagnosis of primary melanoma include the absence of other primary site melanomas and no history of the removal of a melanoma or atypical melanocytic lesion from the skin or other organs (3).
S-100 proteins and HMB-45 antibodies are very sensitive for the diagnosis of melanocytic lesions. Immunohistochemical examination of the tumor from this patient revealed a positive reaction with S-100 proteins and HMB-45 antibodies, which led us to assume a primary MM of the stomach. MMs that arise in mucosal surfaces appear to be more aggressive and associated with a worse prognosis than cutaneous MMs. This poorer prognosis may be related to late diagnosis, an inherently more aggressive behavior of mucosal MM, or earlier dissemination because of the rich lymphatic and vascular supply of GI tract mucosa (3,7).
The clinical manifestations of primary gastric melanoma are similar to those of other gastric tumors, with weight loss, upper gastrointestinal bleeding, and anemia as the most common symptoms. Most patients are asymptomatic until the tumor becomes advanced and so the prognostic is poor (1,4).
For the diagnosis of early stages of gastric carcinoma it is important to collect biopsies from several areas of the gastric stump, even if a carcinoma is not suspected macroscopically. Endosonography can show the degree of infiltration into the gastric wall or infiltration of the surrounding organs with an accuracy of 85%. The diagnosis of lymph node metastasis is more difficult. Screening for gastric malignancies with tumor markers has not proved to be very sensitive, because there are no specific tumor markers for gastric cancer (7).
In conclusion, although neuromalignancy classically manifests insidiously, it can present abruptly with acute onset symptoms and signs. This case revealed a Melanomatous Leptomeningeal Carcinomatosis masquerading as Guillain-Barré Syndrome. CSF analysis and early MR spinal imaging are crucial tools in the diagnostic work-up of paraparesis and in guiding subsequent management. Elevated CSF protein levels with evidence of leptomeningeal hemorrhage (old or new) should arouse the suspicion of malignancy, in particular melanoma, which has a recognized propensity for metastasizing to the CNS and bleeding. Primary gastric melanoma is an extremely uncommon clinical entity. Amelanotic melanoma such as the one in this case can be missed in poorly differentiated tumors unless appropriate staining tests are performed. Primary malignant melanoma of the stomach may be an underdiagnosed and early detection and surgical intervention is critical for long-term cure, though overall prognosis is very poor.
REFERENCES
Contributed by Alcidea da C. Rosa, MD; Marcus Vinicius Pinto, MD; Victor Hugo R. Marussi MD; Nathalie H. Silva Canedo, MD, PhD; Luiz Felipe R. Vasconcellos, MD, MSc.
International Society of Neuropathology