Metastatic Tumors Of Unknown Origin Research Articles

Metastatic tumours of oral cavity - A clinico pathological appraisal of six cases

Background : Tumors metastasizing to the oral and maxillofacial region are rare and contribute to about 1% of all malignancies. Oral metastases usually occur in advanced stages of cancers. Mandible is the most common site for metastasis. It is a great challenge for a clinician to diagnose a metastatic lesion due to lack of pathognomonic signs and symptoms. Dental surgeons play an important role in patients where oral metastasis is the first sign of undiscovered cancer in other parts of the body. Aim: The aim of this study is to analyse the clinical, radiological and histopathological features of metastatic lesions to the oral & maxillofacial region. Materials And Methods: A total of 6 different histopathologically diagnosed cases of metastasis to the oral cavity were included in this study. Clinical demographic profile, radiographic findings, histopathological findings, treatment and follow up data were recorded and analysed.Results: All the cases included in the study were histopathologically diagnosed as metastatic tumors. The age of occurrence was in the range of 40 to 70 years and involved 3 males and 3 females. 4 cases had extra oral swelling as the clinical presentation. 4 cases involved the mandible. Radiolucent lesions involving the bone were seen in 87% of the cases.Conclusion: Based on the cumulative clinical data from the 6 cases, identification of metastatic tumors were based on histopathological findings correlating with the clinical radiographic and other investigations. Early diagnosis of the metastatic tumors of unknown origin could improve the chance of survival of patients.

Complete remission of Cdx-2 positive primary testicular carcinoid tumor: 10-years follow-up and literature review

BackgroundThe neuroendocrine cells can cause a variety of malignancies throughout the human body known as the neuroendocrine tumors (NETs) or carcinoid tumors. The primary testicular carcinoid tumor (PTCT) accounts for less than 1% of the testicular neoplasms and for only 0.2% of all carcinoid tumors representing already a very rare neoplastic entity. Here, we present a patient with a history of an exceptionally rare primary testicular carcinoid tumor, staining positive for Cdx-2 along with a literature review.Case presentationA 44-year old patient without significant past medical history was diagnosed in September 2009 with primary testicular carcinoid tumor, which was surprisingly staining positively for Cdx-2, too. At the time of the initial diagnosis the tumor was already showing histopathological infiltration of veins. DOTA-TATE-PET/CT imaging and endoscopy studies did not show any signs of distant metastases and in particular no gastrointestinal manifestation following no further medical indication for systemic chemotherapy. The continuous and close follow-up of the patient has reached a total of over 10 years at the time of publication remaining in complete remission.ConclusionThe diagnosis of primary testicular carcinoid is based on histopathology. The detailed histopathologic assessment of biomarkers based on immunohistochemistry is very important for the classification and the prognosis of the primary testicular carcinoid tumor. Primary testicular carcinoid tumor with Cdx-2 positive stain outlines an exceptionally rare neoplastic entity without a consensus about general follow-up guidelines, requiring close clinical and imaging aftercare and consideration in Cdx-2 positive metastatic tumor of unknown origin.

76. THE ROLE OF FRAILTY IN PREDICTING POSTOPERATIVE SOCIOECONOMIC OUTCOMES AMONG PATIENTS WITH METASTATIC BRAIN CANCER

BACKGROUNDPatient frailty is an important consideration in the context of providing high-value, cost-effective care, as it has shown to effectively predict postoperative morbidity and mortality in many surgical subspecialties. However, for metastatic cancer patients, there is a lack of consensus as to whether frailty effectively predicts postoperative outcomes such as survival and length of stay (LOS), specifically among patients with metastatic brain tumors.OBJECTIVEThe present study sought to determine if the 5-factor modified frailty index (mFI-5) independently predicts LOS, discharge disposition, and total hospital charges among patients with metastatic brain cancer.METHODSPatients diagnosed with metastatic brain cancer who underwent surgery between 2017–2019 at a single academic institution were analyzed. Bivariate analysis identified patient characteristics significantly associated of LOS, discharge disposition, and total hospital charges. Multivariate linear regression was used to identify independent predictors of LOS and total hospital charges, while multivariate logistic regression was used to identify independent predictors of non-routine discharge disposition. P <0.05 was considered statistically significant.RESULTSA total of 302 patients were included in our analysis. Our patient cohort had a mean age (standard deviation) of 62.27 11.86 years, and was majority female (52.0%) and Caucasian (74.2%). The majority of patients had a primary lung cancer (24.8%), followed by breast cancer (13.6%). There was no significant difference in mFI-5 score between patients with metastatic tumors of known origin compared to patients with metastatic tumors of unknown origin (p=0.61). In multivariate analysis, a higher mFI-5 score independently predicted longer LOS (regression coefficient [Coef]=1.36 days, p<0.001), non-routine discharge disposition (odds ratio [OR]=1.60, p=0.0079), and higher total hospital charges (Coef=$4325.54, p=0.0010).CONCLUSIONThe mFI-5 independently predicts LOS, discharge disposition, and total hospital charges among our cohort of metastatic brain cancer patients. Our findings may be used to aid physicians in providing high-value neurosurgical care.

Comparison of clinical results of decompression/fusion surgery for paralysis caused by metastatic spinal tumors of unknown versus known origin.

Objective: Whether or not emergent decompression/fusion surgery for paralysis caused by metastatic spinal tumors of unknown origin improves patient neurological outcome and survival remains unclear. This study aimed to evaluate the clinical outcomes of emergent decompression/fusion surgery for paralysis caused by spinal tumors of unknown or not previously diagnosed origin.Patients and Methods: Data from the medical records of 11 patients with spinal tumors of unknown origin (study group) were compared with those of 15 patients with metastatic spinal tumors of known origin (control group). The outcome measures were postoperative performance status, motor function evaluated with the Frankel grade, and actual survival after surgery as compared with the estimated survival calculated using the Tokuhashi score. χ2 analyses were performed to evaluate differences between the groups.Results: The mean performance status was 3.6 preoperatively, which improved to 2.9 postoperatively (P<0.05), in the unknown origin group and 3.6 preoperatively, which improved to 2.7 postoperatively (P<0.05), in the control group. Seven patients (64%) in the unknown origin group showed improvement in paralysis by ≥1 Frankel grade. By contrast, only 4 patients (27%) in the control group showed improvement in paralysis. The unknown origin group tended to show better improvement (P=0.05). All the patients in the unknown origin group underwent adjuvant therapy after definitive diagnosis following surgery. The unknown origin group showed a slight tendency toward better survival than toward the estimated survival.Conclusion: Emergent decompression/fusion surgery for patients with paralysis caused by metastatic tumors of unknown origin is potentially useful for diagnosing tumor origin and improving neurological outcomes and performance status, and thus for extending survival.

GATA3 as a putative marker of breast cancer metastasis-A retrospective immunohistochemical study

Diagnostic verification of breast cancer metastasis with histopathology and imaging analysis is essential to determine tumor staging. The aim of this study was to validate the utility of GATA3 immunohistochemistry as a diagnostic marker for breast cancer metastases and metastases of unknown primary origin. Retrospective immunohistochemical analysis of GATA3 expression in 164 breast cancer metastases diagnosed between 2004 and 2014 showed a striking difference between mammaglobin and GATA3 expression (51.2% vs 94% positivity). These findings highlight GATA3 as a more reliable and sensitive diagnostic marker for breast cancer metastases and possibly metastatic tumors of unknown origin than mammaglobin.

A case of S-100 negative melanoma: A diagnostic pitfall in the workup of a poorly differentiated metastatic tumor of unknown origin

When confronted with a metastatic poorly differentiated tumor of unknown origin, the initial workup includes the standard panel of immunostains to rule out carcinoma, sarcoma, lymphoma, and the greatest mimicker in pathology – malignant melanoma. Although not specific, the S-100 protein is expressed in over 95% of malignant melanomas. Herein, we present a case of multiorgan metastatic malignancy with a dominant hilar and mediastinal mass in a current smoker; clinically, highly suggestive of widespread primary lung cancer. This case was eventually classified as malignant melanoma, despite a significant diagnostic challenge due to lack of prior history, unusual cytomorphology, and S-100 protein negativity. A battery of immunostains was performed and the addition of other melanocytic-associated markers confirmed the melanocytic lineage of the neoplasm. This case highlights the pitfalls in the differential diagnosis of a metastatic tumor of unknown origin by fine needle aspiration cytology due to the significant morphologic overlap of poorly differentiated malignancies. We emphasize that, albeit rare, malignant melanomas can be completely negative for S-100 protein and the use of additional melanocytic-associated markers in the differential workup maybe critical in arriving promptly at a proper diagnosis. We also briefly discuss other currently available immunohistochemical markers that can assist in the identification of the S-100 negative melanoma.

Metastases of unknown origin: Principles of diagnosis and treatment

Cancer of unknown primary (CUP) origin refers to patients who present with histologicaly confirmed metastatic cancer in whom a detailed medical history, complete physical examination, including pelvic and rectal examination, full blood count and biochemistry, urinalysis and stool occult blood testing, hisinpathological review oJ biopsy speimens with the use of immunohistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mammography, fail to identify the primary site. The cancer of unknown primary accounts for 3%-5% of all human cancers. The standard diagnostic procedure for the majority of patients includes histopathologic review of biopsy specimens with the use of immunoltistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mamography, fail to identify the abdomen and pelvis. The four common histologic diagnoses are: adenocarcinoma (70%), poorly differentiated carcinoma (20%), squamous carcinoma (10%), and poorly differentiated neoplasms (5%). The prognosis for most patients with unknown primary tumors is poor, with survival often less than 6 months from diagnosis. Based on clinical and pathologic features, approximately 40% of patients can be categorized within subsets for which specific treatment has been defined. Empiric therapy is an option for the remaining 60% of patients. Metastatic tumors of unknown origin have a unique clinical presentation due to a specific biology. Insight into the molecular biology of unknown primary tumors will be essential for the development of more effective treatments.

Expression of CDX2 in benign tissue and adenocarcinoma of the prostate

Numerous studies have claimed that CDX2 is relatively specific and sensitive in establishing a gastrointestinal origin in metastatic tumors of unknown origin. We have recently seen 2 cases of prostatic adenocarcinoma (PCa) on needle biopsies with diffuse strong nuclear staining for CDX2 sent for consultation. One case was a prostatic duct adenocarcinoma in a man with a prostate-specific antigen (PSA) value of 327 ng/mL, and the other was a PCa with a Gleason score (GS) of 4 + 4 = 8 in a man with a PSA value of 15 ng/mL. An adenocarcinoma with GS 3 + 3 = 6 from the contralateral side did not express CDX2. Because documented examples of this phenomenon are rare, we investigated the immunoexpression of CDX2, using tissue microarrays (TMAs). Three slides of TMAs were used to stain 708 tissue samples (0.6 mm in diameter) containing either benign or malignant prostate tissue, as well as control tissues from various anatomical sites including colon. In total, 195 samples of primary PCa with GS of 6 (n = 41), 7 (n = 21), and 8 (n = 8); 195 samples of benign prostate tissue; and 185 samples of metastatic PCa were studied. Of 70 radical prostatectomy specimens examined for PCa in TMAs, 4 (5.7%) were positive for CDX2, showing Gleason score of 6 (n = 3) and Gleason score of 7 (n = 1). Focal moderate positive staining was seen in benign prostate tissue in 7 (11.7%) of 60 radical prostatectomy specimens. None of the metastatic PCa expressed CDX2. CDX2 may uncommonly be focally expressed in benign prostatic glands. Staining in PCa is less common and appears independent of GS and is usually patchy and focal and of lesser intensity than in colonic tissue. However, rarely strong and diffuse staining may be seen. Positive CDX2 staining in high-grade prostate cancer (ductal, cribriform, and solid) may be confused with secondary carcinoma of colonic origin. Routine histopathology, positive PSA immunostaining, and clinical findings can help confirm the correct diagnosis.

Expresión de Citoqueratina 5 y Calretinina en el carcinoma renal de células claras

PurposeCytokeratin 5 (CK5) and calretinin have been useful in different studies as immunohistochemical markers suggestive of mesothelioma, and their expression is analyzed for the histological differential diagnosis with adenocarcinomas, specially when confronting with metastatic tumors of unknown origin. We have analyzed the expression of CK5 and calretinin in clear cell renal cell carcinoma MethodsA series of 63 clear cell renal cell carcinomas was studied. 46 of these cases were embedded in two tissue arrays, and a second group, of 17 cases, was constituted by conventional paraffin blocks from high-grade tumors (grade 4 of Fuhrman)Immunohistochemical staining was performed with monoclonal antibodies against CK5 and calretinin, following the labeled sptreptavidin-biotin technique ResultsNo positivity for calretinin was observed in any case, while CK5 was focally expressed, in an isolated group of cells, in 1 of the 63 cases (1,59%) which corresponded to a high-grade carcinoma (grade 4 of Fuhrman) ConclusionsExpression of calretinin was not observed in clear cell renal cell carcinoma and positivity for CK5 occurred only in one case, in a very small proportion of tumor cells. Therefore, in practice, although the positivity for these markers cannot completely exclude renal cell carcinoma, this result is very rare in this tumor and other diagnostic posibilities should be considered

A case with widespread cutaneous metastases of unknown primary origin: Grave prognostic finding in cancer

We present a 52-year-old man with widespread cutaneous metastases (CMs) of unknown primary origin. Although we performed many of the investigations, we could not find out a primary origin of malignancy. There are no practical algorithms to identify the primary of cutaneous metastatic tumors of unknown origin. An algorithm in cancer patients with CMs seems to be needed to manipulate such cases. We believe that more reports related with this issue must be published to form an algorithm in such cases.

A Case of Primary Central Nervous System Lymphoma: Crucial Implication in Multiphasic Physical and Brain Check-up.

We report a 75-year-old man with primary central nervous system (CNS) lymphoma which was detected on the first physical and brain check-up. He developed headache, depression and the loss of body weight for recent two months, and received multiphasic health check-up in our institute. On brain check-up (Stratis II, Hitachi Medical Co., Japan), T2-weiiiihed imaginnnng revealed multiple hyperintense signal areas in the periventricular white matter and basal ganglia. The differential diagnosis between brain tumors and multiple lacunar infarctions was needed because he had hypertension and severe degree of diabetes mellitus. Fluid-attenuated inversion recovery imaging disclosed markedly multiple hyperintense mass lesions. Gadolinium-enhanced T1-weighted imaging showed strong and homogenous enhancement. Brain tumor was confirmed by these features of MRI. Physical check-up showed no advanced malignant tumors in other organs. At first, brain metastatic tumor of unknown origin was suspected on physical and brain check-up. The definite diagnosis of primary CNS lymphoma was made by stereotactic brain biopsy in a University hospital. He was recovered after administration of steroid and radiotherapy. Primary CNS lymphoma was detected in one of 2, 312 adult subjects who received brain check-up between April 1, 2001 and January 31, 2002 in our institute. This unique case points out that multiphasic health tests, including simultaneous brain check-up, contribute to the early discover of fetal brain tumors. The combined data of physical and brain check-up could have benefits for the selection of further laboratory studies and therapeutic strategy in patients with brain tumors.

Metastatic uveal melanoma. A morphologic and immunohistochemical analysis.

Uveal melanoma often metastasizes late and preferentially to the liver, in contrast to cutaneous melanoma. The objective of the current study was to evaluate the histopathologic and immunohistochemical changes in primary uveal melanomas and their corresponding metastases. The morphology and immunohistochemical reactivity for the melanoma-associated antibodies HMB-45, S-100 protein, and NKI-C3 were assessed for 29 primary uveal melanomas and their corresponding metastatses. A significant difference in cell type of the primary and the metastatic uveal melanoma was found (P = 0.0001). The metastases derived from the 29 patient's revealed 82.5% epithelioid or nonclassifiable cells. Positive staining of the primary uvea melanomas and their metastases was found to be 93% and 91%, respectively, for HMB-45, 80% and 66%, respectively, for S-100, and 56% and 71%, respectively, for NKI-C3. Metastases of uveal melanomas are comprised of a higher grade of malignant cell types. Nonclassifiable cells can be observed in 40% of metastatic lesions. In the current study, HMB-45 proved to be the most sensitive immunohistochemical marker in the analysis of metastatic uveal melanoma and should be used as part of a panel of monoclonal antibodies in the analysis of any metastatic tumor of unknown origin.

骨病変を呈した成人Ｔ細胞白血病の２例

We experienced two cases of bone lesions associated with ATL as the primary sites. Case 1 was a 45-year-old man who complained of right hip joint pain. Radiographically, there was an osteolytic lesion in the femoral neck. The patient was positive for HTLV-I antisera and ATL like cells were found in his peripheral blood. Biopsy of the femoral neck demonstrated a Non-Hodgkin lymphoma, diffuse pleomophic cell type. We therefore diagnosed ATL of bone origin. Case 2 was a 62-year-old man who complained of neck pain and eruption. On X-ray, C3 was compressed and biopsy of the eruption, positive HTLV-I antisera and examination of the peripheral blood all confirmed the diagnosis of ATL.Since ATL with bone lesions as the primary site is easily misdiagnosed as a metastatic tumor of unknown origin, careful diagnosis is needed in patients with bone lesions from an unknown primary site.

Prognostic and diagnostic implications of estrogen and progesterone receptor assays in cytology.

Scientific evidence suggests that cancer is a consequence of genetic changes that result in uncontrolled cellular growth, tissue invasion, and metastasis. This concept has led to a great deal of excitement in the medical community in the hope that precise identification of genes involved in human cancer could potentially facilitate our understanding of human malignancies. It may also be possible to apply this information directly to different clinical settings. Many technologies are now available which offer opportunities for pathologists to not only expand their diagnostic abilities, but also to assess the prognosis of a given tumor in a specific patient. These include immunocytochemistry, flow cytometry, cell image analysis, and molecular genetic studies. In this review, the role of immunocytochemical hormone receptor assay as an aid in tumor prognosis and in prediction of tumor response to endocrine therapy will be discussed. Emphasis will be placed on the use of hormone receptor assay as an adjunct in diagnostic pathology and in assessment of metastatic tumors of unknown origin. The potential value of assessment of hormone receptors in different cytologic preparations will also be discussed.

Use of monoclonal antibody for assessment of estrogen and progesterone receptors in malignant effusions.

An immunocytochemical assay utilizing specific monoclonal antibodies against estrogen receptor (ER) and progesterone receptor (PgR) has been shown to be highly reliable for the detection of hormone receptors in hormone sensitive tumors. To assess the usefulness of this technique in malignant effusions, CytospinR (Shandon, Inc., Pittsburgh, PA 15275), preparations of 41 pleural and ascitic fluid were studied. The findings from the malignant cells employing estrogen and progesterone receptor immunocytochemical assay were compared with the results obtained from primary tumors by biochemical (dextran-coated charcoal) assay. The results agreed in 88% for ER and 83% for PgR. This study supports the potential value of cytochemical technique in detection of hormone receptors in malignant effusions. Assessment of hormone receptors in malignant effusions may be of clinical significance, particularly in situations where the hormone receptor status of the original tumor is not known. This information may also have some diagnostic and therapeutic importance in assessment of patients presenting with metastatic tumors of unknown origin.

Metastatic tumors of unknown origin

The clinical appearance of metastatic lesions without an obvious primary source for the tumor is a common event. Tumor Registry figures and epidemiologic data grossly understate the actual frequency of unknown primaries, because primary sites are often "assigned" to patients on a best-guess basis without positive proof of a tumor's origin. In the majority of patients whose primary tumors have continued to elude detection, the extensive use of diagnostic imaging studies fails to produce information that alters the patients' clinical course. Rare exceptions will be cited, but these exceptions prove the general rule. Imaging studies should therefore be targeted for selected patients with disseminated malignancies in whom identification of their primary tumors could benefit quality of life or length of survival.

Placental-like alkaline phosphatase reactivity in human tumors: An immunohistochemical study of 520 cases

Placental-like alkaline phosphatase (PLAP) activity has been reported in various human neoplasms of both somatic and germ cell types. The expression of PLAP was examined with a polyclonal antibody and the immunoperoxidase technique in formalin-fixed, paraffin-embedded sections of 37 germ cell neoplasms and 483 somatic tumors. The expression of keratin and epithelial membrane antigen (EMA) was concurrently assessed to determine whether these stains were helpful in distinguishing germ cell neoplasms from somatic tumors that might mimic them microscopically. All germ cell lesions were reactive for PLAP, but so were 62 somatic carcinomas, usually in female müllerian, intestinal, and lung cancers and less often in carcinomas of the breast and kidney. PLAP-reactive somatic tumors exhibited EMA and keratin positivity in the absence of prior protease digestion, whereas germ cell neoplasms failed to do so. Malignant mesotheliomas were nonreactive for PLAP, as were carcinomas of the nasopharynx, adrenals, liver, pancreas, stomach, prostate, and urinary bladder. PLAP is a highly sensitive but nonspecific immunohistologic marker of germ cell differentiation. However, non-protease-enhanced stains for keratin and EMA allow separation of germ cell and somatic carcinomas, despite their shared capacity for PLAP expression. In somatic neoplasms, PLAP immunoreactivity might be of potential use in predicting possible primary sources for metastatic tumors of unknown origin.

Study of nitrosourea glycosyl analogs—V. An oriented phase II trial of RFCNU

Fifty-seven patients with digestive tract tumors or metastatic tumors of unknown origin were treated in a phase II trial with RFCNU [chloro-2-ethyl-1-ribofuranosyl-(isopropylidine-2′-3′-paranitrobenzoate-5′)3-nitrosourea] administered on a two-day schedule. Doses were based on the results of a phase I trial, and ranged from 300 to 350 mg/ m 2. When hematological tolerance was excellent, the dose was escalated to 570 mg/ m 2. In cases of documented bone-marrow intolerance, we decreased the total dose to below 300 mg and even gave only 150 mg/ m 2 to one patient. Courses were repeated every month. Three complete remissions (CR) and five partial regressions (PR) were achieved among 57 patients available for assessment of response. The overall rate of major responses (CR + PR) (PR being regressions superior to 50%) was 14%, with a median duration of 9 months. These major responses included 4 cases of liver metastases (including 2 CR) and 3 lung metastases of colorectal carcinoma (one CR). The responses were obtained at doses in excess of 275 mg/ m 2. We also obtained 30% CR + PR in the case of a metastasis of unknown origin. This above evaluation is severe because it only reports major responses according to the WHO-EORTC-NCI recommendation. We also mention in complement 12% responses inferior to 50% in colorectal cancers, one in a stomach carcinoma, one in a hepatoma and 15% more in metastasis of unknown site primary tumors. The hematological toxicity was mild. It consisted of thrombocytopenia 18%, which was only dose-limiting in 3 patients (6%) previously treated with other nitrosoureas. Leukopenia with white cell counts of 1500/ mm 3 was rarely observed. In 32 previously untreated patients, no correlation was found between hematologic toxicity and the number of cycles administered. Nausea and vomiting were noticed in 14% of patients. These results indicate that the efficacy of RFCNU for digestive tract tumors is at least comparable and probably slightly superior to that of other nitrosoureas. Adverse reactions, and mainly with hematological toxicity, were less marked that those observed with BCNU, CCNU or MeCCNU and do not appear to be cumulative.