|Year : 2017 | Volume
| Issue : 6 | Page : 576-581
Rare presenting features of carcinoma of stomach – Leptomeningeal carcinomatosis, breast metastasis, malignant pleural effusion, and dermatoses: A report of two cases and review of literature
Dhruv Pankaj Mehta, Murtaza Bohra, Asha S Anand, Sonia Parikh, Sandip A Shah
Department of Medical and Paediatric Oncology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
|Date of Submission||14-Sep-2016|
|Date of Acceptance||02-Nov-2016|
|Date of Web Publication||17-Jan-2018|
Dr. Asha S Anand
Department of Medical and Paediatric Oncology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat
Source of Support: None, Conflict of Interest: None
Gastric cancer can have protean manifestations, usual symptoms mimicking those of peptic ulcer disease. Gastric adenocarcinomas have rarely been reported with leptomeningeal carcinomatosis (LMC) and dermatoses as initial presenting features. It is also difficult to diagnose breast metastasis of gastric carcinoma due to its rarity. We report two such cases with rare initial presentation. Our first case was a 46-year-old male who presented with LMC. Our second case was a 24-year-old male whose initial complaints were shortness of breath, bilateral breast lumps, and skin discoloration. Both cases on further investigations were found to have primary tumors in the stomach.
Keywords: Bony metastases, gastric adenocarcinomas, leptomeningitis, mammary tumors, pleural effusion
|How to cite this article:|
Mehta DP, Bohra M, Anand AS, Parikh S, Shah SA. Rare presenting features of carcinoma of stomach – Leptomeningeal carcinomatosis, breast metastasis, malignant pleural effusion, and dermatoses: A report of two cases and review of literature. Med J DY Patil Univ 2017;10:576-81
|How to cite this URL:|
Mehta DP, Bohra M, Anand AS, Parikh S, Shah SA. Rare presenting features of carcinoma of stomach – Leptomeningeal carcinomatosis, breast metastasis, malignant pleural effusion, and dermatoses: A report of two cases and review of literature. Med J DY Patil Univ [serial online] 2017 [cited 2020 May 27];10:576-81. Available from: http://www.mjdrdypu.org/text.asp?2017/10/6/576/223361
| Introduction|| |
In India, incidence of gastric cancer (3.8/100,000) is overall less than the worldwide incidence. The age-adjusted rate of gastric cancer among urban registries in India is 3.0–13.2/100,000. At the time of diagnosis, only 24% of stomach cancers are localized, 30% have lymph node involvement, 35% with distant metastasis with 4%–14% having liver metastasis. Leptomeningeal carcinomatosis (LMC), also known as carcinomatous leptomeningitis, is dissemination and growth of malignant cells throughout the pia mater and the arachnoid membrane. LMC occurs in only 3%–8% of all cancer patients but is associated with devastating neurologic complications with high mortality. The prevalence of gastric cancer-induced LMC is as low as 0.16%–0.69%. LMC is usually a manifestation of advanced or metastatic cancer, with peritoneal and liver metastasis generally occurring prior to it, rather than an early presentation. Metastases to breast from extramammary neoplasms are rare, with only 43 cases of breast metastasis from gastric cancer being reported. Pleural effusion is usually seen in already diagnosed gastric cancer patients., Dermatoses associated with visceral malignancies are indicative of widespread dissemination of tumor with early mortality. Herein, we present two cases of gastric carcinoma with LMC, breast metastasis, malignant pleural effusion, and skin involvement as initial presentation without preceding gastrointestinal (GI) symptoms such as weight loss, anorexia, fatigue, epigastric discomfort, pain, postprandial fullness, heartburn, indigestion, nausea, or vomiting.
| Case Reports|| |
A 46-year-old male with no previous comorbidities presented to our hospital with severe headache, dizziness, vomiting, and easy fatigability. There were no other significant findings in the medical history such as seizures, focal neurological deficits, or abdominal pain and symptoms of gastric cancer such as weight loss, epigastric discomfort, heartburn, and indigestion. His family history was negative for malignancies. On examination, he was oriented to time, place, and person. His vitals were within normal range. No lymph nodes were palpable. On neurological examination, there were no focal neurological signs or abnormal reflexes. There was no neck stiffness or nystagmus. The sensory examination was normal. There was no evidence of spinal tenderness or cord compression. Fundus examination was normal with no evidence of papilledema. The conjunctivae had minimal icteric tinge. Rest of the systemic examination was normal. The symptoms were slightly improved with conventional analgesic agents. The laboratory tests are given in [Table 1]. All viral hepatitis markers were absent. Initial ultrasound examination of the abdomen and pelvis was normal, except for few para-aortic lymph nodes. The magnetic resonance imaging (MRI), MR angiography, and venography of the brain showed no abnormalities. In view of persistent intractable headache with nausea and vomiting, a lumbar puncture with analysis of cerebrospinal fluid (CSF) for routine, microscopy, and cytology was performed. The CSF glucose concentration was 53.2 mg/dl, protein content of 12 mg/dl, chloride concentration of 118.8 mmol/l, leukocyte count of 4 cells/mm3 with 100% polymorphs. CSF cytology examination revealed atypical cells suspicious for malignancy. A repeat CSF cytological analysis was positive for metastatic adenocarcinoma. The diagnosis of LMC was made and search for primary tumor began. The patient's chest X-ray was normal. A whole-body position emission tomography (PET)-computed tomography (CT) scan was conducted. It showed increased 18F-fludeoxyglucose (FDG) uptake in left supraclavicular, left posterior cervical, para-aortic, and mesenteric lymph nodes. Left supraclavicular lymph node biopsy revealed metastatic adenocarcinoma with signet ring cell component [Figure 1]. Immunohistochemical stain was positive for CK7, carcinoembryonic antigen (CEA) and negative for thyroid transcription factor-1 (TTF-1) and CK20 supporting the diagnosis of metastatic adenocarcinoma with possible primary from upper GI tract. Endoscopy revealed 2 cm × 1 cm malignant ulcer involving antrum of stomach with gastric stasis. Histopathological examination of biopsy from ulcer also showed mucinous adenocarcinoma with signet ring cell [Figure 2]. The patient was started on supportive care, steroids, and mannitol. On stabilization, patient was given biweekly intrathecal chemotherapy with methotrexate 15 mg, cytarabine 70 mg, and hydrocortisone 50 mg. He was started on GEMOX Chemotherapy (gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 every 14 days as a 28 day cycle) in view of deranged liver function tests. However, on the 10th day of hospital stay, the patient developed generalized tonic–clonic seizures. He became stuporous and his condition deteriorated rapidly. The patient died the next day.
|Figure 1: H and E section (×40) obtained from biopsy of left supraclavicular lymph node of first patient showing adenocarcinoma|
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|Figure 2: H and E section (×10) obtained from upper gastrointestinal endoscopy guided biopsy of stomach mucosa showing adenocarcinoma infiltrating into submucosa of stomach|
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A 24-year-old male with no family history of any malignancy and with no previous comorbidities presented to us with chief complaints of progressive shortness of breath on exertion, bilateral breast painful swellings, and bluish-red discoloration of skin of the chest and upper abdomen. There was no history of chest pain, vomiting, weight loss, fever, or cough. On clinical examination, the patient was in New York Heart Association Grade III dyspnea, with respiratory rate of 32/min. He had blood pressure of 102/66 mmHg and pulse rate of 110/min. Pulse oximeter showed saturation of 94% on room air. There was no pallor, icterus, or pedal edema but mild nonpitting edema of the right upper limb. Right axillary lymph node, nontender, firm to hard in consistency measuring 2 cm × 3 cm was palpable. Furthermore, right inguinal lymph node measuring 1.5 cm × 2.5 cm was palpable. On respiratory system examination, trachea was central with use of accessory muscles of respiration. There was dullness on percussion with decreased breath sounds at right hemithorax. There was diffuse induration with minimal tenderness on bilateral breast examination. Reddish blue confluent papules with desquamation were present on his chest and upper abdomen suggestive of erythroderma [Figure 3]. The laboratory tests are given in [Table 1]. Chest X-ray showed bilateral pleural effusion, the right more than the left side. Pleural fluid was sent for cytological analysis. It was positive for malignant cells [Figure 4]. Immunohistochemical stain was positive for AE1, CK7 (in occasional cells), and CEA while it was negative for CK20, leukocyte common antigen (LCA), and estrogen receptor with possibility of metastatic adenocarcinoma primarily from the upper GI tract. Contrast-enhanced CT scan of the thorax, abdomen, and pelvis [Figure 5] revealed the following: heterogeneously enhancing soft tissue density lesions in both breasts in retroareolar region with largest measuring 20 × 22 mm on right side, multiple lymph nodes in bilateral supraclavicular region with largest measuring 11 × 15 mm on right side, bilateral axillary lymph nodes with largest measuring 32 × 22 mm on right side, multiple enlarged lymph nodes in preparatracheal, prevascular, precarinal, subcarinal, aorto-pulmonary window, and right hilar region with largest measuring 21 × 17 mm in precarinal region, multiple lymph nodes along bilateral iliac vessels and bilateral inguinal region with largest measuring 19 × 30 mm in right inguinal region, 8 × 7 mm hypodense lesion in spleen with possibility of metastasis, lytic sclerotic metastasis in multiple visualised bones, right mild pleural effusion with maximum thickness of 17 mm and left moderate pleural effusion with collapse of left lower lobe. Fine needle aspiration cytology from left areolar swelling and from right axillary lymph node was positive for metastatic adenocarcinoma [Figure 6]. Excisional biopsy of right inguinal lymph node revealed metastatic poorly differentiated adenocarcinoma with immunohistochemical stain being positive for epithelial membrane antigen and CEA while negative for AE1, CK7, LCA, CD20, CD117, TTF-1, CK20, and vimentin. Upper GI endoscopy revealed the presence of thickened, edematous, and hyperemic mucosa with reduced distensibility of lesser curvature of stomach. Biopsy from lesser curvature of the stomach was also positive for poorly differentiated adenocarcinoma. In view of right upper limb swelling, venous Doppler was carried to rule out venous thrombosis. However, it showed normal Doppler signals in both arteries and veins, subcutaneous edema, and iso to hypoechoic lesions along vessels, largest measuring 9 mm × 6 mm. The patient was given supportive care to relieve his symptoms. Right chest tube drainage was done to relieve his dyspnea. However, patient refused further treatment and follow-ups and he took discharge against medical advice.
|Figure 3: Photograph of the second patient showing erythrodermic lesions on the anterior chest wall and upper abdomen with swelling of right breast. Informed consent was taken from the patient for clicking and publication of this photograph|
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|Figure 4: H and E cytology slide (×100) obtained from pleural fluid showing adenocarcinoma cells in the second patient with mitoses, increased nuclear/cytoplasmic ratios, pleomorphic nuclei, prominent nucleoli, and hyperchromatism dispersed singly and in small clusters|
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|Figure 5: Computed tomography to scan section of case report 2 showing retroareolar right breast soft tissue lesion measuring approximately 20 mm × 22 mm|
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|Figure 6: H and E cytology slide (×40) obtained by fine needle aspiration of breast swelling in the second patient positive for adenocarcinoma cells with increased nuclear/cytoplasmic ratios, hyperchromatism, and mitoses|
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| Discussion|| |
Despite all the recent changes in screening, diagnosis, treatment, and surveillance, gastric cancer still remains the second most common cause of cancer mortality in Asia. Carcinomas of the stomach can spread by local extension to involve adjacent structures and can have lymphatic, peritoneal, and distant metastases. Because of the vague, nonspecific symptoms that characterize gastric cancer, many patients are diagnosed with advanced-stage disease. LMC is dissemination and growth of malignant cells throughout the pia mater and the arachnoid membrane by propagation in CSF. Meningeal involvement as presenting symptom of malignancy is rare, with most patients diagnosed with LMC being prior cancer diagnosis. LMC occurs in only 3%–8% of all cancer patients, with prevalence of gastric cancer-induced LMC being as low as 0.16%–0.69%., The rate of LMC in breast cancer, lung cancer, and melanoma is 12%–14%, 10%–26%, and 17%–25%, respectively. The various routes of spread of tumor cells to leptomeninges suggested are arterial circulation, retrograde flow in Batson's venous plexus, spread through perineural spaces, perivascular spaces, or lymphatics, and direct infiltration from bone metastases. The presenting manifestations of LMC are commonly nonspecific and variable due to mutifocal involvement of meninges, thus making early diagnosis challenging task. The various symptoms and signs include headache, nausea, vomiting, ataxia, dizziness, alteration in mental status, motor weakness, seizures, bilateral progressive blindness, and bilateral hearing loss. LMC is usually a manifestation of advanced or metastatic cancer, with peritoneal and liver metastasis generally occurring prior to it, rather than an early presentation. The main diagnostic procedures for LMC are CSF cytological examination and neuroimaging. CSF cytological examination is required for definitive diagnosis of LMC, but it is invasive procedure and its sensitivity is suboptimal. It has been reported that sensitivity of single lumbar puncture is only 54% which increases to 91% on multiple repeated taps. As in our first case, definite evidence of metastatic adenocarcinoma was obtained on the second lumbar puncture. Among neuroimaging studies, MRI is the main choice for the diagnosis of LMC as it has 1.5–2 times higher specificity and sensitivity than CT scans; however, false negative MRI findings are seen in 30% of cases  (as was in our first case too). In the first case, whole-body PET/CT was performed to track the primary disease, but it revealed only multiple pathological lymph nodes, both above and below the diaphragm. In gastric cancer, approximately half of the primary tumors are FDG-negative, the diffuse (signet cell) subtype being the most likely cause (due to decreased expression of the glucose transporter-1). Our first case too had signet ring cell morphology explaining nil detectability on FDG-PET. On histopathological examination of primary gastric cancer, poorly differentiated adenocarcinoma with signet ring cell features is the most common cause of LMC. Treatment strategy for LMC includes intrathecal chemotherapy with methotrexate, cytarabine, thiotepa, and hydrocortisone, radiotherapy, and best supportive care. Some reports have shown that intrathecal chemotherapy may prolong the survival compared to those on best supportive care, but the median overall survival for LMC with either methotrexate or cytarabine remains dismal at 3–4 months only., Palliative radiotherapy in patients with severe neurological dysfunction, best supportive care for patients with poor performance status, and systemic chemotherapy in patients with better performance status can be given. We too administered GEMOX protocol with biweekly triple intrathecal chemotherpy to our first case. The median survival in untreated patients is 4–6 weeks, which in some cases may increase to 4–6 months with aggressive treatment. However, the overall prognosis of patients with LMC remains dismal.
Lung cancer is one of the leading causes of malignant pleural effusion accounting for approximately one-third of all malignant effusions and breast cancer being the second most common cause. Gastric adenocarcinoma is the most frequent cause of malignant pleural effusion among GI malignancies. Roussos et al. recorded four cases wherein malignant pleural effusion was the initial presentation. In all these cases, hepatic metastasis was present; however, our second case report would be the first case wherein malignant pleural effusion was present without hepatic metastasis. The mean survival time for these four cases was 3 months. Pleural effusion is usually seen in already diagnosed gastric cancer patients.,
Metastases to breast from extramammary neoplasms are rare accounting for 0.3%–2.7% of all malignant mammary tumors, with only 43 cases of breast metastasis from gastric cancer been reported. The most common sources of breast metastases are melanomas and lymphomas, followed by carcinomas of the lung, ovary, kidney, stomach, oropharynx, and carcinoid. Of the 43 cases reported, all except one patient were females, ours being the second case report in male. Only one patient of 43 cases was younger than our second patient with her age being 22 years, and she was also the only patient among other cases to histopathological diagnosis of poorly differentiated adenocarcinoma similar to our patient. Of 43 patients, 29 (67.4%) had histological diagnosis of signet ring cell carcinoma. Of 43 patients, 21 (48.8%) had palpable breast nodules as in our second case. Bilaterality was noted in 10/43 (23.3%) patients. Of 43 patients, 13 (30.2%) were found to have breast metastasis simultaneously with primary gastric tumors or within 1 year of diagnosis. The overall prognosis of the patients with breast metastasis of gastric adenocarcinoma was poor with majority dying within 1 year.
Erythroderma as part of paraneoplastic dermatosis is associated with numerous visceral tumors of esophagus, stomach, colon, gallbladder, lung, kidney, prostate, and nasopharynx. It is estimated that 0.6%–9% of all internal organ malignancies have skin involvement at some point in time. For dermal metastasis from GI neoplasms, colon is the most common site, followed by stomach, esophagus, and small intestine. The presence of skin involvement signifies widespread disease and portends poor prognosis, with median survival of 3 months after detection of cutaneous metastasis.
Our second patient also had numerous bony metastases without its clinical symptoms such as bone pains or pathologic fracture. It has been reported that bone metastasis of gastric carcinoma occurs more frequently in poorly differentiated adenocarcinoma of body of stomach with abundant regional lymph node metastasis without hepatic metastasis, as was in our case. This has been explained by the difference in metastatic route, with well-differentiated adenocarcinomas metastasizing through portal vein and poorly differentiated carcinomas primarily through vertebral veins. Bone metastasis, mostly osteolytic in nature, is also more prevalent in younger age group. The most frequent sites of bone metastasis were vertebrae (89%), ribs (63%), scapula (10%), lower extremities (10%), and upper extremities (5%). The median survival of patients with bone metastasis has been reported to be approximately 3 months from the diagnosis.
The second patient also had lymphedema of the right upper limb. This can be explained by micrometastasis of gastric carcinoma cells obstructing or infiltrating into the lymphatic networks of the dermis. To the best of our knowledge, the second case is the first of its kind report in English medical literature of virulent presentation of gastric carcinoma.
| Conclusion|| |
Gastric cancer is exerting a significant health and economic burden in India. Understanding various metastatic manifestations of gastric carcinoma will help in understanding the biology of its various subtypes and guide research in its management. LMC is rare but extremely fatal complication of gastric cancer that commonly manifests as headache. Early recognition with high index of suspicion is needed to ameliorate the symptoms and initiate early appropriate treatment. Upper GI endoscopy should be considered as a diagnostic tool in patients of malignant pleural effusion of unknown origin, especially if pleural fluid cytology is suggestive of adenocarcinoma. For patients to receive timely treatment, it is important to distinguish metastatic breast cancer from primary breast cancer. It is also anticipated that the survival period as well as the quality of life may be improved with making a rapid diagnosis of bony metastasis of gastric cancer.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]