Adenocarcinoma Of Unknown Primary Origin Research Articles

Autopsy diagnosis of diffuse intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC), a severe liver cancer, makes up to 20% of all hepatic malignancies and is difficult to diagnose early due to its often asymptomatic nature. This case report documents a rare presentation of ICC with multiple diffuse nodules not previously recorded in medical literature. A 65-year-old man with no significant medical history presented with back pain, anorexia, and significant weight loss. Elevated tumor markers and enlarged lymph nodes were observed, though imaging did not reveal a primary liver mass. Diagnostic efforts, including computed tomography and positron emission tomography scans and biopsies of lymph nodes and bone marrow, suggested adenocarcinoma of unknown primary origin. A definitive diagnosis was only made post-mortem, revealing multiple diffuse nodules in the liver identified as ICC, marking a rare presentation without a primary mass. This case highlights the diagnostic challenges posed by atypical ICC manifestations, where typical imaging does not indicate a primary mass, delaying diagnosis and treatment. The findings emphasize the importance of considering ICC in differential diagnoses in cases of unknown primary adenocarcinoma with liver involvement. The discovery of ICC with diffusely infiltrative nodules underscores the necessity for comprehensive diagnostic evaluations in patients presenting with nonspecific systemic symptoms and abnormal liver findings.

Delayed Recognition of Levetiracetam-induced Pancytopenia.

Levetiracetam can cause both acute and delayed-onset pancytopenia through bone marrow suppression.The phenomenon is normally reversible and blood counts improve with drug cessation.Clinicians should consider checking a complete blood profile within a month of drug initiation, particularly in high-risk patients.

Presumed disseminated carcinomatosis of the bone marrow in a dog

An eight-year-old male neutered Jack Russell terrier presented with fever, shoulder and elbow pain and progressive right forelimb lameness. Haematology revealed a non-regenerative anaemia and marked thrombocytopenia. Radiography and CT...

Identification of a metastatic lung adenocarcinoma of the palate mucosa through genetic and histopathological analysis: a rare case report and literature review

BackgroundCancers of unknown primary origin (CUPs) are reported to be the 3-4th most common causes of cancer death. Recent years have seen advances in mutational analysis and genomics profiling. These advances could improve accuracy of diagnosis of CUPs and might improve the prognosis of patients with CUPs.Case presentationA 76-year old male with an adenocarcinoma of unknown primary origin in the lung presented with another tumor of the palate mucosa. The tumor cells in the pleural effusion were all negative for immunohistochemical markers (TTF-1 and Napsin A) and lung-specific oncogenic driver alterations (EGFR mutation and ALK translocation). The tumor of the palate mucosa was likewise identified as an adenocarcinoma, and the cells showed cytological similarities with the tumor cells in the pleural effusion; TTF-1, Napsin A, EGFR mutation and ALK translocation were all negative. This result suggested that origins of the tumors of the palate mucosa and in the lung were the same, even though the origin had not yet been determined. Next, we addressed whether the tumor of the palate mucosa was a primary tumor or not. Secretory carcinoma (SC), which is a common type of minor salivary gland tumor (MSGT), was suspected; however, mammaglobin was negative and ETV6-NTRK3 (EN) fusion was not observed. Other MSGTs were excluded based on histological and immunohistochemical findings. Furthermore, an additional examination demonstrated an oncogenic KRAS mutation at codon 12 (p.G12D) in both palate tumor and in pleural effusion. KRAS mutation is known to exist in one-third of lung adenocarcinomas (LUADs), but quite rare in MSGTs. The possibility of metastasis from other organs was considered unlikely from the results of endoscopic and imaging studies. This result indicated that the primary site of the CUP was indeed the lung, and that the tumor of the palate mucosa was a metastasis of the LUAD.ConclusionsA tumor of the palate mucosa that showed diagnostic difficulties was determined to be a metastatic LUAD by genomic alterations and histopathological findings.

Association between survival and maximum standardized uptake value of liver metastases detected by 18-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography in patients with adenocarcinoma of unknown primary origin.

The objective of this retrospective study is to investigate the association between survival and maximum standardized uptake values (SUVmax) of liver metastases detected by pre-treatment positron emission tomography-computed tomography (PET-CT) in patients with adenocarcinoma of unknown primary origin (ACUP). A total of 58 patients with ACUP and liver metastases confirmed histopathologically by liver biopsy and pre-treatment PET-CT were included in this study. SUVmax values of the liver lesions were measured and their association with survival was investigated. The median age was 62years; 63.8% of the patients were males and 36.2% were females. The median overall survival was calculated as 10.7months (OS). The median SUVmax of the liver metastases was 8.6. Accordingly, two groups were established: one with values <8.6 and the other with ones ≥8.6. No differences were detected between the two groups with respect to general characteristics. Median OS was 13.2months in the group with SUVmax <8.6 compared to 7.4months in the group with SUVmax ≥8.6. This difference was statistically significant (p=0.033). SUVmax (HR 1.104, 95% CI 1.013-1.204, p=0.025), age (HR 1.033, 95% CI 1.002-1.064, p=0.034), presence of chemotherapy (HR 2.296, 95% CI 1.136-4.641, p=0.021) and LDH level (HR 1.002, 95% CI 1.001-1.003, p=0.007) were identified as independent prognostic factors affecting survival in the multivariable analysis. This is the first report evaluating the impact of SUVmax for liver metastases on ACUP patient survival. The SUVmax of liver metastases evaluated by PET-CT is a prognostic factor influencing survival of patients with ACUP.

The Association Between Survival and Maximum Standardized Uptake Value of Liver Metastases Detected By 18-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography-Computed Tomography in Patients with Adenocarcinoma of Unknown Primary Origin

Objective The objective of this retrospective study is to investigate the association between survival and maximum standardized uptake values (SUVmax) of liver metastases detected by pre-treatment positron emission tomography-computed tomography (PET-CT) in patients with adenocarcinoma of unknown primary origin (ACUP).

Опухоль брюшной стенки – грыжа Спигелевой линии, содержащая метастатическую карциному с невыявленным первичным очагом

Опухоль брюшной стенки – грыжа Спигелевой линии, содержащая метастатическую карциному с невыявленным первичным очагом

Management eines retrorektalen Tumors unter Berücksichtigung einer seltenen Differenzialdiagnose

We present a case of a retrorectal space occupying lesion diagnosed as an adenocarcinoma of unknown primary origin by preoperative histopathology. Localization slightly above the anal sphincter would have required extirpation of the rectum. Rectal palpation, endosonography and radiological imaging, however, suggested a retrorectal tumor or a metastasis of an adenocarcinoma. Both entities would have required local resection. We applied a surgical algorithm including frozen biopsy allowing a stepwise choice of operative procedure from the spectrum in question. The operation performed was thus tailored to the entity of the tumor.

Gastrointestinal Cancer Educational Case Series: Management of Metastatic Adenocarcinoma of Unknown Primary Origin in a Ph+ ALL Survivor

Secondary malignancies and chronic end-organ sequelae are significant and steadily rising consequences of cancer therapy. The workup and management of a carcinoma of unknown primary must consider the patient's clinical presentation, radiologic and pathologic findings, and comorbidities. We present the case of a 50-year-old female survivor of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with significant treatment-related end-organ sequelae who developed a metastatic adenocarcinoma of unknown primary 15years following curative therapy for her ALL. The complex management issues related to the investigations and choice of therapy for this patient are reviewed. This case discusses key issues related to the workup and management of a carcinoma of unknown primary. In addition, it illustrates the importance of taking patient comorbidities into consideration and tailoring investigations and therapy accordingly.

Gene Expression Profiling to Identify the Histogenetic Origin of Metastatic Adenocarcinomas of Unknown Primary

Patients with adenocarcinoma of unknown primary origin (ACUP) constitute approximately 4% of all malignancies. For effective treatment of these patients, it is considered optimal to identify the primary tumor origins. Currently, the success rate of the diagnostic work-up is only 20% to 30%. Our goal was to evaluate the contribution of gene expression profiling for routine clinical practice in patients with ACUP. Formalin-fixed, paraffin-embedded (FFPE) samples were obtained from 84 patients with a known primary adenocarcinoma and from 38 patients with ACUP. An extensive immunohistochemical panel classified 16 of the patients with ACUP, whereas 22 patients remained unclassified for their histogenetic origin. Information about staging procedures and clinical follow-up were available in all patient cases. The expression data were analyzed in relation to clinicopathologic variables and immunohistochemical results. The gene expression-based assay classified the primary site correctly in 70 (83%) of 84 patient cases of primary and metastatic tumors of known origin, with good sensitivity for the majority of the tumor classes and relatively poor sensitivity for primary lung adenocarcinoma. Gene expression profiling identified 15 (94%) of 16 patients with initial ACUP who were classified by immunohistochemistry, and it made a valuable contribution to a potential site of origin in 14 of the 22 patients with ACUP. The gene expression platform can classify correctly from FFPE samples the majority of tumors classes both in patients with known primary and in patients with ACUP. Therefore, gene expression profiling represents an additional analytic approach to assist with the histogenetic diagnosis of patients with ACUP.

Diagnosis of Poorly Differentiated Thyroid Cancer with Radioiodine Scanning after Thyrotropin Alfa Stimulation

To the Editor: Poorly differentiated thyroid cancers are rare and can be difficult for surgeons, endocrinologists, and pathologists to identify.1 These cancers fall into two main histologic categories: insular and other (large cell). Most, but not all, stain with thyroglobulin or thyroid transcription factor 1; those that do not represent particular diagnostic challenges.1–3 We describe a 60-year-old man who presented with bilateral cervical lymphadenopathy and an enlarged thyroid. Biopsy specimens of cervical nodes and the thyroid gland showed features of poorly differentiated adenocarcinoma of unknown primary origin — possibly pulmonary, colorectal, pancreatic, or thyroidal. Immunostaining for thyroglobulin and thyroid . . .

Immunohistochemistry in diagnostic surgical pathology of the prostate

Immunohistochemistry (IHC) can play an important role in diagnostic surgical pathology of the prostate. Basal cell markers, such as the 34betaE12 antibody and antibodies directed against cytokeratin 5 and 6 or p63, are very useful for demonstration of basal cells as their presence argues against a diagnosis of invasive prostatic carcinoma (PC). However, several benign mimickers of PC, including atrophy, atypical adenomatous hyperplasia (AAH), nephrogenic adenoma, and mesonephric hyperplasia, can stain negatively with these markers, and thus, a negative basal cell marker immunostain alone does not exclude a diagnosis of benignancy. Although there are examples in the literature of high grade PC that stain focally with some of the basal cell markers, these cases are usually readily diagnosed based on H&E appearances and are unlikely to be confused with these benign mimickers. Alpha-methylacyl-coenzyme-A racemase (AMACR) is a sensitive marker of PC (except for a few uncommon variants: atrophic, foamy gland, and pseudohyperplastic variants), and its detection by immunohistochemical staining in atypical prostatic lesions can be very useful in confirming an impression of adenocarcinoma. AMACR expression can also be identified in high grade prostatic intraepithelial neoplasia (PIN), prostatic atrophy, AAH, and benign prostatic glands, and accordingly, a diagnosis of PC should not be based solely on a positive AMACR immunostain, especially when the luminal staining is weak and/or noncircumferential. The use of AMACR/basal cell antibody cocktails has been found to greatly facilitate the distinction between PC and its benign mimickers, especially when only limited tissue is available for staining. Prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP) are both quite sensitive and fairly specific markers of PC (there are a few nonprostatic tumors that can express one or both), and are both very helpful in establishing or confirming the diagnosis of PC when the differential diagnosis includes other tumors that can involve the prostate such as urinary bladder urothelial carcinoma. 34betaE12, p63, thrombomodulin, and uroplakin III are additional urothelial associated markers useful in this differential diagnosis. CDX2 and villin are useful markers to diagnostically separate colonic adenocarcinoma from PC. AMACR positivity and negative basal cell marker reactions are useful to confirm the presence of residual PC after hormonal or radiation therapy. Pan-cytokeratin, PSA, and PSAP can also highlight subtle infiltrates of PC with hormonal or radiation therapy effect. PSA and PSAP immunohistochemical stains are valuable in confirming metastatic carcinoma as being of prostatic origin and should always be utilized in the diagnostic evaluation of metastatic adenocarcinoma of unknown primary origin in males.

Phase I/II study of liposome-complexed mitoxantrone in patients with advanced breast cancer.

The toxicity of escalating doses of liposome-complexed mitoxantrone (LCM) was evaluated in 22 women with histological/cytological diagnosis of metastatic breast cancer (21 pts) or adenocarcinoma of unknown primary origin (1 pt). All patients but one had been pretreated with chemotherapy. LCM was given IV as a 1h-infusion, repeated every 3 weeks, from a starting dose of 3 mg/m2, corresponding to 1/3 of the MELD10. An intra-patient dose escalation scheme, with an increase per cycle of 3 mg/m2 up to 12 mg/m2, and then by 2 mg/m2 was applied, treatment being continued until tumour progression, or toxicity, or up to a maximum of 6 cycles, whichever occurred first. Granulocytopenia was dose-limiting, with a GNC count of less than 0.5 x 10(3)/microliters after 30%, 28%, 50% and 50% of the cycles given at 16, 18, 20 and 22-24 mg/m2, respectively. The lowest GNC count occurred usually 2 weeks after treatment, with recovery in the following week. Gastro-intestinal toxicity, mucositis and alopecia were rare and of mild degree. Two patients, with a subtotal neoplastic involvement of the liver and a pretreatment grade 4 liver impairment, died because of acute liver failure a few days after treatment. The maximum tolerable dose was defined at 22 mg/m2 and 18 mg/m2, given every 3 weeks for 6 cycles, was the regimen recommended for phase II studies. Seven previously untreated patients with metastatic breast cancer have been so far treated. The pattern of toxicity of LCM (specific, short-lasting granulocytopenia; negligible, non cumulative non hematological toxicity) was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

Metastatic adenocarcinoma to the neck from an unknown primary source

We report a retrospective review of 223 patients who presented to the Department of Head and Neck Surgery from 1970 through 1987 with a diagnosis of metastatic adenocarcinoma of unknown primary origin. Multivariate analysis was performed using the following parameters: age, sex, initial side and site of nodal involvement, involvement of other body sites, degree of differentiation, treatment modality, outcome, and survival. Follow-up was obtained in all patients, with a minimum of 2 years for survivors. Average age was 55 years, with an approximately equal male:female ratio. The most common site of presentation was the supraclavicular fossa (76%). The initial side of presentation was the left neck in 53% of patients, right neck in 33%, and bilateral in 14%. Metastatic disease to other body sites was present in 86% of patients, with the most common sites being mediastinum (35%), lung (21%), and bones (19%). Increased survival was associated with unilateral neck involvement (p = 0.001) and disease limited to nodes above the cricoid cartilage (p = 0.007). Mean survival was 17 months, with a median of 8 months. Death was due to the index cancer in all but four patients; three of these four patients died of treatment-related causes. Survival was 20% at 2 years and 9% at 5 years. Length of survival was not affected by age, sex, initial side of neck disease, location of other metastatic sites, histologic appearance, or treatment modality. Our current algorithm for the work-up and treatment of this lethal disease is explained.

Metastatic adenocarcinoma in the cervical lymph nodes from an occult primary

Cervical lymph node metastases as the only site of disease is a rare presentation of an adenocarcinoma of unknown primary origin. This retrospective analysis examines the records of ten consecutive patients at the Middlesex Hospital with this diagnosis between 1954 and 1986. The diagnostic protocol employed and the results of radical treatment are evaluated. Nine patients received radiation therapy with intent to cure, and one patient had a radical neck dissection. Overall actuarial survival for all patients (10) at 2 years was 23% and at 5 years 0%. Only two of the 10 patients subsequently revealed a primary tumour — both below the clavicles. Disease control above the clavicles was not achieved in a single patient despite radical treatment.

A clinical and pharmacokinetic phase I study of 1,2,4-triglycidylurazol (TGU, NSC 332488)

Twenty-six patients with advanced malignancies received TGU given as an intravenous (i.v.) bolus in physiological saline at 3 weekly intervals. The starting dose was 30 mg/m 2 with standard graded escalations to 900 mg/m 2. Myelosuppression occurred at 800 mg/m 2, with a mean nadir of 2.0 ± 0.8 × 10 9/ l and a mean nadir platelet count of 41 ± 31 × 10 9/ l. At 800 or 900 mg/m 2 nausea and vomiting was WHO grade 0 in 5, grade I in 6, grade II in 11 and grade III in 10 courses of therapy. Alopecia did not occur. TGU was given by i.v. infusion at 800 mg/m 2 in 2 patients, both of whom developed severe thrombophlebitis. Five patients given TGU by i.v. bolus developed mild phlebitis. No renal, hepatic or cardiac toxicity was noted. Two patients had partial responses; both had adenocarcinoma of unknown primary origin, one of whom had been resistant to prior therapy with FAM. An HPLC analytical method was developed with a sensitivity of 250 ng/ml. The data from 7 patients studied best fit a one compartment pharmacokinetic model with an exponential decay and a t 1 2 of only 2.1 min. In conclusion, the dose limiting toxicity of TGU appears to be myelosuppression and we would recommend a dose of 800 mg/m 2 given as an intravenous bolus every 4 weeks for future phase II trials.

Adenocarcinoma of Unknown Primary Origin

Seventy-seven cases of adenocarcinoma of unknown origin were studied retrospectively. Pain was the most common presenting symptom and lymphadenopathy was the most common finding on physical examination. Tumor involved several organs in two thirds of the patients, the lung being the most frequently involved. Complete surgical resection was possible in only four of 27 patients with single organ involvement. All four patients had lymph node dissections and remain free of disease after one to three years. Four patients with tumor confined to the liver received infusion of antitumor agents through the hepatic artery which resulted in objective tumor regression in all, and regression of greater than 50% in two. Forty-three trials of systemic intravenous chemotherapy were administered to 38 patients with nonresectable tumor resulting in greater than 50% tumor regression in eight. Responses were more frequent with regimens containing adriamycin plus either cyclophosphamide or cis-platinum. Median survival of all patients in the study was 31 weeks. Patients who received chemotherapy survived significantly longer (median 41 vs 26 weeks, P = 0.005). Similarly, patients who responded to chemotherapy survived significantly longer than nonresponders (median 54 vs 27 weeks, P less than 0.02). Our results indicate that early treatment of patients with adenocarcinoma of unknown origin improves their prognosis.

Adenocarcinoma of unknown primary site: a clinico-pathological study.

An analysis of the clinico-pathological findings in 49 patients with adenocarcinoma of unknown primary origin indicates a short survival time. No factors were identified that influenced survival. Thromboembolic episodes and second primary tumors commonly complicate the clinical course. Metastases in widespread organs are common autopsy findings. Immunological mechanisms may explain these findings.