Metastatic Carcinoma Of Unknown Origin Research Articles

Hypocalcemia in Setting of Malignancy of Unknown Origin: A Case Report

Background: Hypercalcemia is a common finding well-recognized in up to 30% of cases of malignancy, associated with poor prognosis and advanced disease state. Hypocalcemia, while uncommon, can also be found in cases of malignancy facilitated by its own unique mechanism and etiologies. We present a case of severe hypocalcemia in the setting of malignancy of unknown origin. Clinical Case: 72-year-old female with a history of metastatic carcinoma of unknown origin, followed actively by Oncology, presented acutely with shortness of breath, chest pain, stiff hands and clenched fist. Patient had reported a 20 lbs weight loss over three months with a “knot” in the epigastric area affecting appetite and interfering with eating. Prior CT showed diffuse adenopathy with diffuse permeative bone destruction highly suspicious for malignancy. Follow up PET-CT showed mixed lytic lesion and sclerotic changes throughout the entire skeleton from the skull to mid thighs compatible with osseous metastatic. Initial tests show severe hypocalcemia with appropriately PTH elevation and normal vitamin D25 (calcium 5.5 mg/dL, albumin 3.9 g/dL, phosphorus (PO4) 2.3 mg/dL, magnesium (Mg) 1.5 mg/dL, PTH 243 pg/mL, vitamin D25 31.44 ng/mL). Further workup shows normal creatinine levels (0.88 mmol/L) and elevated alkaline phosphatase (1140 IU/L). Physical exam revealed bilaterally clenched fist and positive Chvostek sign. After two doses of 2 grams calcium gluconate, calcium had improved up to 7.2 mg/dL (corrected 7.76 mg/dL, albumin 3.3 g/dL) with plans to replete Mg and PO4. Patient was started on Calcium-Vitamin-D 500-200 mg-units (Oscal) two tabs trice daily. However, calcium continues to drop the next day with levels at 5.7 mg/dL (corrected 6.42 mg/dL, albumin 3.1 g/dL). A calcium infusion of 10 grams was then given over 16 hours. Calcitriol 0.25 mg twice daily was started. 24-hour urine study showed low calcium excretion (<0.8 mg/dL), normal Mg excretion (6.5 mg/dL) with an adequate creatinine collected (0.6 grams) showing no deficiencies in kidney resorption. Prior to discharge, patient’s calcium had stabilized (corrected 8.2 mg/dL, albumin 3.4 g/dL) and her associated symptoms had resolved. She was discharged on Oscal 2 tabs 4 times daily and Calcitriol 1 mcg twice daily. Conclusion: Given these biochemical results and imaging evidence of bone metastases, this case highlights the uncommon findings of hypocalcemia in the setting of malignancy. With the combination of low 24-hour urine calcium, elevated PTH, normal vitamin D25, low PO4, normal kidney function and increased alkaline phosphatase, these findings most likely indicate hypocalcemia secondary to osteoblastic bone metastasis, resulting from deposition of calcium in osteoblastic lesions.

Novel approach to reduce SARS-CoV-2 transmission during trans-oral robotic surgery.

This study describes a novel approach in the reduction of SARS-CoV-2 transmission during trans-oral robotic surgery (TORS). Eight patients underwent TORS between 01 February 2020 and 07 September 2020. A sterile plastic sheet draped over sterile supports with water-tight seal around each cannula was used to create a sterile working space within which the robotic arms could freely move during operation. This set-up acts as an additional physical barrier against droplet and aerosol transmission. Operative diagnosis; droplet count and distribution on plastic sheet and face shields of console and assistant surgeons, and scrub nurse were documented. TORS tumour excision was performed for patients with suspected tonsillar tumour (n = 3) and tongue base tumour (n = 2). TORS tonsillectomy and tongue base mucosectomy was performed for cervical nodal metastatic carcinoma of unknown origin (n = 3). Droplet contamination was noted on all plastic drapes (n = 8). Droplet contamination was most severe over the central surface at 97.2% (91.7–100.0%), with the highest droplet count along the centre-most column where it overlies the site of operation in the oral cavity 33.3% (n = 31). Droplet count decreased towards the periphery. Contamination rate was 2.8% (0.0–8.3%) over the right lateral surface. There was no droplet contamination over the vertex and left lateral surface of plastic drapes. No droplet contamination was noted on face shields of all parties. The use of sterile plastic drapes with water-tight seal around each robotic cannula can help reduce viral transmission to healthcare providers during TORS.

The role of Hepatocyte nuclear factor 4 alpha HNF4α and Homeobix protein CDX2 immunomarkers in the diagnosis of metastatic colorectal carcinoma

Background: Detection of the primary site of metastatic carcinoma of unknown origin is necessary to help in the choice of the treatment. CDX2 is routinely used in metastatic adenocarcinomas cases for identifying the gastrointestinal origin. HNF4α is a new immunohistochemical marker with a few studies showing that it is expressed in a majority of colorectal adenocarcinomas. Aim: To determine the expression of HNF4α and CDX2 in metastatic carcinoma cases for detection of gastrointestinal origin. Material and methods: We assessed HNF4α and CDX2 in 60 metastatic carcinoma cases in different organs, which were diagnosed retrospectively. HNF4-α and CDX-2 expressions were evaluated by light microscopic examination of all tissue sections by two different pathologists. The cut-off for positivity of HNF4α and CDX-2 was 1% of stained nucleus of metastatic tumor cells. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of two markers and P value were calculated. Results: The calculated sensitivity, specificity, positive predictive value, negative predictive value and accuracy of HNF4α were 90%, 82.5%, 72%, 94.3% and 85% respectively for diagnosis of colorectal carcinoma metastasis from other metastatic carcinomas. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CDX2 were 80%, 72.5%, 59.3%, 87.9% and 75% respectively. The P-value for comparing between their expression in metastatic adenocarcinoma from lower GIT and each other groups is less than 0.05. Conclusions: We concluded that HNF4α can be used as a supplementary marker with CDX2 to identify metastatic colorectal adenocarcinoma. HNF4α expression is a highly specific and sensitive marker of colorectal origin.

Conservation of personal protective equipment for head and neck cancer surgery during COVID-19 pandemic.

BackgroundCOVID‐19 pandemic has led to a global shortage of personal protective equipment (PPE). This study aims to stratify face shield needs when performing head and neck cancer surgery.MethodsFifteen patients underwent surgery between March 1, 2020 and April 9, 2020. Operative diagnosis and procedure; droplet count and distribution on face shields were documented.ResultsForty‐five surgical procedures were performed for neck nodal metastatic carcinoma of unknown origin (n = 3); carcinoma of tonsil (n = 2), tongue (n = 2), nasopharynx (n = 3), maxilla (n = 1), and laryngopharynx (n = 4). Droplet contamination was 57.8%, 59.5%, 8.0%, and 0% for operating, first and second assistant surgeons, and scrub nurse respectively. Droplet count was highest and most widespread during osteotomies. No droplet splash was noted for transoral robotic surgery.ConclusionFace shield is not a mandatory adjunctive PPE for all head and neck surgical procedures and health care providers. Judicious use helps to conserve resources during such difficult times.

Uncommon skeletal metastasis secondary to transitional cell carcinoma

Background:Canine transitional cell carcinoma (TCC) is the most common type of malignant tumor of the urinary system. This tumor rarely metastasizes to bones, and dogs most commonly present with lower urinary tract signs.Case Description:An 8-year-old female spayed beagle presented with unilateral front-limb lameness in which pain was localized to the shoulder joint. Surgical bone biopsy following abnormal radiographic lesions noted in the scapula was consistent with metastatic carcinoma of unknown origin. Abdominal ultrasound revealed a mass in the trigone region of the urinary bladder, which was cytologically confirmed to be a transitional cell carcinoma. Amputation was elected due to severity of the limb pain, and chemotherapy for the TCC was scheduled to follow after healing from surgery was complete. At the 2-week recheck for commencement of chemotherapy, the patient was anemic and a pathologic fracture was found on the L5 vertebra. Due to poor prognosis, the owner elected for humane euthanasia.Conclusion:This case report documents the clinical and pathological findings of a dog where metastasis to a rarely documented distant bone site secondary to TCC was diagnosed before the primary tumor. The unusual sequence of events described in this case report is a reminder to always consider all the possible differential diagnoses, as that may influence our recommendation on diagnostics and treatment.

Accuracy of Diagnostic Methods for Detection of Head and Neck Primary Origin in Metastatic Neck Mass

Background and Objectives It is important to localize the primary site when cervical lymph node metastasis is detected. The purpose of this study was to evaluate the accuracy of diagnostic methods to detect the head and neck primary site in patients with metastatic neck mass. Subjects and Method Sixty-six patients who had presented with neck mass and were confirmed to have metastatic carcinoma by fine needle aspiration cytology from January 1998 to June 2016 were enrolled. We analyzed the accuracy of diagnostic modalities that inluded physical and endoscopic examination, CT, MRI, PET/CT, and guided biopsy. Results The mean age of patients was 58.7±12.6 years with the male to female ratio of 55:11. The metastatic lymph nodes were most common at level II (60/66, 90.9%) followed by levels III, IV, I and V. The most common primary site was tonsil (45.5%), followed by the nasopharynx, base of tongue and hypopharynx, and eight patients (12.1%) were diagnosed as metastatic carcinoma of unknown origin. The primary sites were detected by: physical and endoscopic examination in 36/66 (54.5%), CT in 41/66 (62.1%), MRI in 39/52 (75%) and PET/CT in 46/63 (73.1%). The primary sites were additionally detected using PET/CT for nine cases of the 20 cases, where primary sites were not found using physical and endoscopic examination, CT or MRI. Guided biopsy was done in 11 cases, where primary sites were not detected by all of the methods; hence, primary sites for 3 cases were additionally revealed. Conclusion PET/CT is a useful method when physical examination, CT and MRI cannot reveal the primary site of metastatic neck mass. Guided biopsy can be performed when primary site is not founded by any of the physical and imaging examinations. Key words: Diagnosis ㆍ Guided biopsy ㆍ Head and neck cancer ㆍ Metastatic neck mass ㆍ Unknown primary tumor

A rare case of prostatic ductal adenocarcinoma presenting as papillary metastatic carcinoma of unknown primary: A case report and review of the literature

Prostatic ductal adenocarcinoma is an uncommon form of prostatic carcinoma. We report a case of a 63-year-old man who presented with non-infective thrombotic (marantic) endocarditis and an incidental finding of a destructive lesion in the left iliac crest. Core biopsy of the lesion showed a carcinoma with papillary architecture and was initially diagnosed as “metastatic carcinoma of unknown origin”. The patient experienced a cerebral infarction and expired six days later. Postmortem examination revealed extensive mixed acinar and ductal adenocarcinoma (Gleason score 5+4=9) in the prostate. Further studies confirmed the bone lesion as metastatic prostatic ductal adenocarcinoma. Although rare, metastatic prostatic adenocarcinoma should be considered in the differential diagnosis in a male patient when the carcinoma shows predominantly papillary architectures. A review of literature is presented to enhance the awareness of this entity.

False Positive Radioiodinated Metaiodobenzylguanidine ((123)I-MIBG) Uptake in Undifferentiated Adrenal Malignant Tumor.

123I-Metaiodobenzylguanidine (123I-MIBG) scintigraphy is a widely used functional imaging tool with a high degree of sensitivity and specificity in diagnosis of pheochromocytoma. However, rare cases of false positive reactions have been reported. A 67-year-old male patient was admitted with epigastric pain. Abdominal computed tomography (CT) revealed a heterogeneous left adrenal mass 6 cm in diameter; following hormone testing, 123I-MIBG scintigraphy was performed to determine the presence of pheochromocytoma, which confirmed eccentric uptake by a large left adrenal gland mass. Chest CT and PET-CT confirmed metastatic lymphadenopathy; therefore, endobronchial ultrasound transbronchial needle aspiration was performed. Metastatic carcinoma of unknown origin was suspected from a lymph node biopsy, and surgical resection was performed for definitive diagnosis and correction of excess hormonal secretion. A final diagnosis of undifferentiated adrenal malignant tumor was rendered, instead of histologically malignant pheochromocytoma, despite the uptake of 123I-MIBG demonstrated by scintigraphy.

Rozsiany ziarniniak obrączkowaty u pacjenta z przerzutami raka płaskonabłonkowego do węzłów chłonnych o nieustalonym ognisku pierwotnym – opis przypadku

Rozsiany ziarniniak obrączkowaty u pacjenta z przerzutami raka płaskonabłonkowego do węzłów chłonnych o nieustalonym ognisku pierwotnym – opis przypadku

(68)Ga-DOTATATE PET/CT in the evaluation of patients with neuroendocrine metastatic carcinoma of unknown origin.

There is little evidence regarding the role of (68)Ga-DOTATATE PET/CT for the identification of primary tumors in patients with metastatic neuroendocrine carcinoma of unknown primary. The aim of this study is to assess the value of this technique in the mentioned clinical scenario. We retrospectively studied twenty-nine patients (mean age 59.5 ± 10.6 years; female 17) with pathologically proven neuroendocrine metastases. In all cases conventional imaging was negative for primary tumor identification. (68)Ga-DOTATATE PET/CT was performed with a mean dose of 104.2 ± 18.8 MBq, using a 64-slice PET/CT with time-of-flight correction. A team of an experienced radiologist and a nuclear medicine physician evaluated the images. The maximum SUV (SUVm) was measured in all abnormal foci. Histopathology (when available) and/or clinical follow-up with correlative imaging was considered as reference standard. (68)Ga-DOTATATE PET/CT identified the primary tumor in 17/29 (59%) patients in the following locations: pancreas (n = 7), ileum (n = 7), duodenum (n = 1), colon (n = 1) and stomach (n = 1). In this population a significant correlation was found between SUVm of primary tumor and metastases (r = 0.815, P < 0.0001). Furthermore, additional sites of unsuspected metastases were demonstrated in 9 patients of this group and in 6 patients in whom no primary tumor was localized, mainly in lymph nodes and mesentery. Pathology confirmation was obtained in 7 patients who underwent surgery, whereas in the remaining 10 patients, correlative imaging and follow-up confirmed primary tumor localization. (68)Ga-DOTATATE PET/CT is a clinically useful imaging technique for the localization of primary tumors in patients with neuroendocrine metastatic carcinoma of unknown origin with the potential of having a significant impact in patient management and therapy planning.

Rapid development of migratory, linear, and serpiginous lesions in association with immunosuppression

A 78-year-old Bulgarian woman presented to the National Institutes of Health (NIH) with a diagnosis of poorly differentiated metastatic carcinoma of unknown origin. The prior month she had been seen at a hospital in Bulgaria for weight loss and a right inguinal mass. NIH pathology review confirmed a poorly differentiated carcinoma with extensive necrosis suggesting squamous cell carcinoma. She was enrolled in a treatment trial at NIH with metastatic disease invading the lungs and lymph nodes (mediastinum, abdomen, and pelvis) and a chemotherapy regimen was started of gemcitabine, carboplatin, and lenalidomide with dexamethasone as an antiemetic. The patient returned on day 8, and a rash of 2 days duration was noted. Immediately before arriving at the dermatology clinic, she developed altered mental status with aphasia and was admitted for neurologic observation. The altered mental status resolved and evaluation revealed only small-vessel ischemia. The patient was also experiencing diarrhea and was found to have elevated transaminases (4- to 7-fold over normal). Chemotherapy was held because of the transaminase abnormalities and altered mental status. The following day, the patient was seen by dermatology for a progressive asymptomatic eruption.

Death by Subdural Hematoma with Metastatic Carcinoma of Unknown Origin: An Autopsy Case Report

Dural metastasis associated with chronic subdural hematoma is very rare in patients with malignant neoplasms; it may be difficult to distinguish malignant neo- plasms from chronic subdural hematoma. Chronic subdural hematoma is usually a late manifestation of malignant tumors, which contributes to the severity of the progno- sis. The scans obtained by using magnetic resonance imaging or computed tomogra- phy may be misleading when a subdural hematoma masks the underlying tumor. Herein, we report a case of a subdural hematoma with dural metastasis of unknown origin in a 45-year-old woman; however, the neoplasm was not detected until autopsy.

Aggressive clinical course of epithelioid angiosarcoma in the femur: a case report

BackgroundEpithelioid angiosarcoma is a rare variant of angiosarcoma, and is characterized by an epithelioid morphologic appearance that mimics carcinoma. These tumors usually arise in extraskeletal sites; origination in bone is rare.Case presentationA 69-year-old woman presented with right knee pain. Plain radiographs and magnetic resonance imaging showed an osteolytic lesion with a large soft-tissue extension into the distal femur. Under a diagnosis of metastatic carcinoma of unknown origin based on the biopsy specimen, resection and replacement with an artificial joint were performed. Histologic analysis of the resected material confirmed epithelioid angiosarcoma, supported by immunoexpression of cytokeratins and vascular markers. Three months after surgery, metastasis to the bone and lymph nodes was observed, and the patient died of the disease shortly thereafter.DiscussionEpithelioid angiosarcoma of bone is characterized by an aggressive clinical course. A possibility of epithelioid angiosarcoma of bone should be considered in cases with such epithelial features, particularly if only small specimens are available.

PP118: Squamous odontogenic tumour: Report of a rare case and review of the literature

Squamous odontogenic tumour (SOT) was first described in 1975, by Pullon et al. as a rare, benign odontogenic tumor arising in close physical relationship to the dentition from the epithelial rests of Malassez in the periodontal ligament or gingival epithelium. To date, less than 50 cases have been described in the literature. We describe a case of SOT which was histologically misdiagnosed as a metastatic carcinoma of unknown origin. In the discussion and review of the literature that follows, the features of SOT, the differential diagnosis and the appropriate treatment are described.

Inflammatory Metastatic Carcinoma of Sternum Mimicking Sternal Osteomyelitis with Gas Gangrene

Anterior chest wall pain and swelling associated with inflammatory symptoms may be related to the inflammatory process such as infections and arthritis (1). Occasionally, an underlying pathologic process, such as malignancy, can be missed if the symptoms clearly implicate an infection. It can lead to catastrophic results for both the patient and the clinician. Here, we report an elderly male patient initially presenting as gas gangrene in the pectoralis major muscles and osteomyelitis of the sternum and finally diagnosed as metastatic carcinoma of unknown origin of the sternum.

Next Generation Therapy in Chronic Myeloid Leukemia

TKIs Imatinib is an established first-line therapy CP of CML. Before Imatinib therapy, IFN-alpha was a treatment option for CML because it induced durable remissions in a subset of CP patients. However, because of IFN toxicity, and its limited and unpredictable efficacy, IFN-alpha was displaced by Imatinib, with its limited toxicity and marked efficacy in the treatment of most CML patients. Imatinib has limitations, but the 5-year survival rate with Imatinib is approx. 89% compared with Interferon and Cytarabin (70%). About 15–20% CML become resistant to Imatinib, and the resistance is found in association with a BCR/ABL mutation T315I or with G250E mutations. Treatment of Imatinib-resistance CML is thus a challenge in clinical hematology. In addition, clinical evaluation of Imatinib has shown adverse effects, such as fatigue, severe nausea, vomiting, oedema, fluid retention, muscle cramps, muscular skeletal pain, and cutaneous disorders. With the prolonged survival time in CML, which with Imatinib is a median 40 months, BCC, SCC, melanoma (30% cases), breast cancer (the authors have found 1 case), prostate cancer (1 case), GI cancer, GU bladder cancer including RCC, a few pancreatic and cholangiocarcinomas, and metastatic carcinoma of unknown origin have also been reported in various literature [1]. These investigators concluded that increased rates of cancers were found at a large range of sites and there was immune deficiency, regardless of the mechanism of deficiency. There have also been scattered reports of co-existence of CML with other lymphoid malignancies such as CLL and multiple myeloma [1, 2]. It has also been shown that heart failure occurs in 1 in 1,000 patients receiving Imatinib, and that it also alters bone metabolism. Imatinib costs more than the Interferon + Cytarabin combination. The effects of Imatinib (as well as other kinase inhibitors) on leukemic stem or initiating cells are limited, and so it has been advisable to take a low dose of Imatinib over a long period. Now, the second generation TKIs, such as Dasatinib and Nilotinib, have appeared. A unique spectrum of adverse events has occurred and been reported for both these TKIs [3, 4]. For Dasatinib-treated patients, the occurrence of pleural effusion has been a clinical challenge, especially when pleural effusion becomes recurrent or is accompanied by pericardial effusion, pulmonary hypertension, or an infection. Also, potential risk factors such as a pre-existing cardiac disease, arterial hypertension, or auto-immune disorders have been described for these TKIs. Several non-hematologic adverse events have been described for Dasatinib, including diarrhea, skin rash, bleeding, viral re-activation, and sometimes also many opportunistic infections, which have been reported in patients receiving Dasatinib at a dose of 270 mg daily. Nilotinib-treated patients have developed increases in pancreatic enzymes, bilirubin, and fasting glucose levels. Other non-hematologic adverse events of Nilotinib include diarrhea, folliculitis-like skin rash, and bleeding. There are a few reports of severe peripheral arterial occlusive disease (PAOD) and other vascular occlusive events (infarction) in patients receiving Nilotinib [3, 4]. Several of these patients developed a rapidly progressive and highly resistant form of PAOD after switching from Imatinib to Nilotinib [3, 4]. The question is whether patients, who had a complete molecular response (CMR or MCyR) to Imatinib or Imatinib in combination with Interferon, could safely stop drug treatment? What should be done with relapses? Do TKIs act then? SCT is still the treatment for CML that is considered to be curative in patients with AP or blast-crisis CML. Other choices which are still in clinical trial include a vaccine called CMLVAX100 which is given along with Imatinib to see if there is an increase in its effectiveness. Research into this and other cancer vaccines is continuing. The oral agent AP24534 also appears to have some activity independent of Bcr-Abl mutation. Cortes and colleagues [5] conducted a trial of AP24534 in patients with refractory CML and other hematologic malignancies. This agent inhibits survival of cell lines expressing Bcr-Abl variants at an inhibitory concentration of less than 40 nM. It also inhibits Flt-3 and c-Src. And this agent has the advantage of being orally administered.

Identification of carcinoma origin by thyroid transcription factor‐1 immunostaining of fine needle aspirates of metastases

Identification of carcinoma origin by thyroid transcription factor-1 immunostaining of fine needle aspirates of metastases To assess the diagnostic potential of thyroid transcription factor-1 (TTF-1) immunocytochemical staining for identifying the origin of unknown primary cancers from fine needle aspiration cytology (FNAC) of metastases. Immunostaining with TTF-1 was conducted on FNACs suggesting metastatic carcinoma in 128 patients with unknown primary tumours as part of the initial diagnostic procedure. The majority of patients (78) presented with neck masses, four had lung lesions and 46 had masses at other locations. The patients' files were reviewed to obtain data on tumour origin. Thirty-seven of 128 (28.9%) cases stained positive with TTF-1. Pulmonary origin of metastases was confirmed in 27 cases, and four lung lesions were primary lung adenocarcinoma. Two patients had primary and one had mestastatic thyroid carcinomas. In two patients, no follow-up data was available. In one patient, the origin of the primary could not be determined at autopsy. TTF-1 was negative in 18 patients with subsequent diagnosis of metastatic pulmonary cancer and in seven patients diagnosed clinically and radiologically as most probably having a lung carcinoma. In 60 TTF-1 negative patients, the primary tumour originated in other organs (34) or remained unknown (26). TTF-1 immunostaining of FNAC in patients with metastatic carcinoma of unknown origin identified primary pulmonary or thyroid carcinomas in nearly a third of cases. Patients with TTF-1 positive metastases could avoid further extensive diagnostic investigations for the origin of the primary site.

Synchronous Bilateral Invasive Lobular Breast Cancer Presenting as Carcinomatosis in a Male

Invasive lobular breast carcinoma is an exceedingly rare neoplasm in men, representing a very small percentage of all male breast cancers. However, it should remain on the differential diagnosis in a patient with metastatic carcinoma of unknown origin. We report a case of a 58-year-old man who presented with increasing abdominal girth and weight loss. A peritoneal biopsy revealed a malignant epithelial neoplastic process focally arranged in a single-file pattern. There was immunohistochemical reactivity for cytokeratin AE1/AE3. E-cadherin, cytokeratin 5/6, prostatic-specific antigen, and leukocyte common antigen immunostains were negative. Subsequent gastric and right iliac bone biopsies revealed a poorly differentiated carcinoma similar in histology and immunophenotype to the previous peritoneal biopsy. Upon a more thorough physical examination, bilateral breast masses and nipple retraction were noted. Biopsies of the masses revealed estrogen receptor-positive, E-cadherin-negative invasive lobular carcinomas with similar histology to all the previous biopsies. This case is unusual in that it represents the first reported case of lobular carcinoma of the male breast presenting as carcinomatosis. The fact that the patient was male prolonged the identification of the primary site. Although a rare neoplasm in a male, breast cancer should be included in the differential diagnosis of a metastatic carcinoma of unknown origin.

PAPILLARY TUMORS OF THE PINEAL REGION

The pineal region is a rare intracranial site for metastasis. We report three patients initially considered to have metastatic papillary adenocarcinoma to the pineal region. On review, these papillary, keratin-positive neoplasms meet the criteria for papillary tumor of the pineal region (PTPR). These neoplasms occurred in three women (age range, 37-55 yr). Imaging studies demonstrated well-circumscribed lesions in the pineal region. All patients presented with obstructive hydrocephalus and symptoms attributable to hydrocephalus and tectal compression. All three patients underwent near total microsurgical resection of the pineal region neoplasm, followed by adjuvant radiotherapy. The two patients with long-term follow-up (56-60 mo) have remained clinically stable without evidence of local or distant recurrence. The first two patients were initially diagnosed as having papillary metastatic carcinoma of unknown origin. The third patient was treated after the recent description of PTPR and met the histopathological diagnostic criteria. Retrospective pathological review of the previous two patients resulted in designation as PTPR. The morphological features of the tumors in our series, along with the clinical presentations, are similar to those in the original description of the PTPR. Our findings agree with the original hypothesis that the cells composing the PTPR are similar to ependymal cells of the subcommissural organ, thus furthering the hypothesis that the PTPR derives from a specialized ependymocyte associated with the subcommissural organ. The two patients with long-term follow-up (56-60 mo) have remained clinically stable without evidence of local or distant recurrence.

Cushing's paraneoplastic syndrome as first manifestation of an adenocarcinoma of unknown origin

Small cell lung cancer is the most common cause of paraneoplastic Cushing's syndrome. The definitive treatment consists in surgical removal of the tumour, which is not possible in most of these cases (they are often diagnosed at advanced stages), and therefore it is frequently necessary adding the drug ketoconazol. We hereby present the case of a patient diagnosed with a metastatic carcinoma of unknown origin associated with two paraneoplastic syndromes: a Cushing's syndrome and a sensitive-motor axonal neuropathy, a very uncommon association.