A case of adenocarcinoma of unknown primary site successfully treated with gemcitabine monotherapy

A 68-year-old female diagnosed with adenocarcinoma of unknown primary site (ACUP) by biopsy of supraclavicular lymph node was admitted to our department because of progressive dyspnea with cough. The diagnosis of multiple lung metastases and malignant pleural effusion was made. Marked elevation of serum CA 19-9 and DUPAN-2 urged us to treat her as a case of pancreatic carcinoma. Gemcitabine monotherapy yielded resolution of symptoms, decline in the level of tumor markers, shrinkage of lung metastases, and disappearance of pleural effusion. After 10 cycles, the chemotherapy was terminated. However, clinical deterioration was observed two months later. The re-treatment with gemcitabine was started, and a good response was obtained again. Gemcitabine monotherapy can be one of the treatment options for ACUP.     

Combination of cisplatin-doxorubicin-cyclophosphamide in adenocarcinoma of unknown primary site: a phase II trial

The purpose of this report is to evaluate toxicity, response, and survival of the cyclophosphamide-doxorubicin-cisplatin (CAP) chemotherapy regimen in patients with adenocarcinoma of unknown primary site (ACUP). Twenty-two patients with ACUP were eligible for this study between June 1992 and April 1999. There were 13 men (59%) and 9 women (41%) with a median age of 53.5 years (range: 29--78 years). Lung (seven), liver (six), vertebral bone site (six), and abdominal nodes (six) were the most common metastatic sites. Treatment consisted of doxorubicin 50 mg/m(2), cyclophosphamide 1,000 mg/m(2), and cisplatin 100 mg/m(2) (CAP), administered every 3 weeks; a total of six courses were planned. Twenty-two patients were assessable for toxicity and 20 patients were assessable for response. Grade III to IV neutropenia was observed in 14 patients (64%); febrile neutropenia occurred in 6 patients (27%) and in 10 cycles (12.5%). Grade III to IV anemia and thrombocytopenia were found in 12 (54.5%) and 9 patients (41%), respectively. Grade III to IV nausea and vomiting was observed in 9 patients (41%). Ten patients, 50% of the assessable population, obtained an objective response, including 3 complete (15%) and 7 partial (35%) responses. The median response duration was 3.9 months (range: 0.5--13.3 months). One patient (5%) had stable disease and 5 patients (25%) had progressive disease. The median overall survival and the median time to progression were 10.7 months (range: 0.4--56.9 months) and 8.8 months (range: 6.6--16.5 months), respectively. The CAP regimen in patients with ACUP had significant activity. This chemotherapy regimen induced a high level of grade III to IV toxicities and could not be considered as a treatment of reference. However, the emergence of long-term survivors among responder patients highlighted the need to search for an active treatment for patients with ACUP.     

Paraneoplastic syndrome of non-small cell lung carcinoma: a case with pancytopenia, leukocytoclastic vasculitis, and hypertrophic osteoarthropathy

Various remote effects of cancer or paraneoplastic syndromes (PNS) are common in lung cancer, and may be the manifestation of the disease or its recurrence. The symptoms may be endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous in nature. Since the symptoms of paraneoplastic syndromes may occur before the local symptoms of the primary tumor, it might be helpful in the early diagnosis of malignancy. We present a 65-year-old man with multiple paraneoplastic syndrome forms consisting of pancytopenia leukocytoclastic vasculitis and hypertrophic pulmonary osteoarthropathy, associated with non-small cell lung carcinoma.     

Second neoplasms in patients with chronic lymphocytic leukemia

Opinion statement Second malignancies occur with increased frequency in patients with chronic lymphocytic leukemia (CLL) regardless of treatment, but they may be more frequent and more aggressive after nucleoside analog therapy of CLL. In as many as 33% of patients with CLL who develop a second malignancy, a spontaneous remission of CLL precedes the diagnosis of the second malignancy by months or years. Richter’s syndrome, whether manifested by anaplastic large cell lymphoma or Hodgkin’s disease, is not truly a second malignancy because the CLL clone appears to be involved. However, all other malignancies developing in patients with CLL appear to be derived from a different clone. CLL and the second malignancy may have a common viral etiology. Second malignancies in patients with CLL should be treated as they would be in patients without CLL.     

Paget's disease primarily involving the scrotum

Three cases of Paget's disease primarily involving the scrotum are reported. One case exhibited positive staining for prostate specific antigen (PSA) and was associated with an underlying, invasive poorly differentiated adenocarcinoma of unknown primary. The other cases were not associated with any underlying or visceral malignancy. The literature on Paget's disease primarily involving the scrotum including clinical presentation, differential diagnosis, treatment, prognosis, and possible histogenetic mechanisms of this disease is discussed.     

Diagnosis and management of multifocal gliomas

Patients who present with multiple cerebral tumors are usually considered as having metastatic disease. If they have a history of a primary cancer in another site, the brain tumors are considered metastases and are usually managed with standard whole-brain radiotherapy. If no primary cancer site is known, a diagnostic work-up is performed, but if no primary site is found, they are still considered as brain metastases from an unknown primary site. Thus, such patients can either have brain biopsy (recommended) for further diagnostic consideration or, occasionally, they can be treated with whole-brain radiotherapy, depending on the age, performance status and wish of the patient. However, in some of these patients the multiple brain tumors represent multifocal glioma rather than metastases, resulting in incorrect treatment. In such cases, various MRI characteristics may be helpful in directing towards the correct diagnosis. Thus, patients who present with multiple brain tumors should not always be considered to have metastatic disease even if they have a previous diagnosis of systemic cancer, and multifocal glioma should be ruled out.     

Hypereosinophilia and metastatic anaplastic carcinoma of unknown primary

The differential diagnosis of eosinophilia may sometimes be difficult. Eosinophilia may occur in a diverse array of conditions from parasitic infestations to malignacies. Idiopathic hypereosinophilic syndrome has also been described. A 65-year-old male patient presenting with eosinophilia of obscure etiology is described in the present report. Three years after the diagnosis of eosinophilia, metastatic anaplastic carcinoma of unknown primary was detected. Differential diagnosis is disscussed briefly. It is stressed that patients with hypereosinophilia of unknown etiology must be screened for malignancy regularly during follow up.     

Metastatic cancers to the neck from undetermined primary sites long-term follow-up

When a patient presents with a mass in the neck, diagnosis by fine needle aspiration cytology is recommended. This allows an accurate diagnosis of malignancy with minimal morbidity. Tissue planes, important in any future definite neck surgery, are not altered, as they would be from an excisional biopsy. Once the diagnosis of metastatic cancer is confirmed, thorough search for the primary tumor must be made. The history, physical examination, and radiographic and laboratory studies must be complete. Finding no origin of tumor, local treatment of the metastases must be done, with the objective being complete eradication of disease. Regular follow-up, with a continual search for the primary malignancy is then recommended. The specifics of this approach and the results of our series are outlined.     

Dermatomyositis and female malignancy

Six female patients, all with dermatomyositis (DM) and malignancy, have been evaluated and followed over a period of up to 6 years. Five patients had malignancy prior to the diagnosis of DM. Two of these five patients had uterine endometrial adenocarcinoma and another two patients had cervical carcinomas (one each adenocarcinoma and squamous cell carcinoma), and one had adenocarcinoma of the breast. In these five patients there was no evidence of malignancy at the time of diagnosis of DM. One of these five patients had an additional primary malignancy (adenocarcinoma of the breast) which complicated her course. An ovarian adenocarcinoma was present in the sixth patient. The ovarian carcinoma was discovered because of progressive cutaneous disease, and resection and chemotherapy led to a partial control of the DM. The patient with adenocarcinoma of the cervix developed metastases which were discovered when the DM became resistant to therapy. Although DM can parallel the course of a malignant disease, this was not generally the case in this group of patients.     

Pediatric primary lung adenocarcinoma in the absence of congenital pulmonary airway malformation

Primary lung adenocarcinoma is a rare entity in the pediatric population, especially in the absence of an underlying congenital pulmonary airway malformation. Primary lung malignancies in pediatric patients are rare and constitute 0.2 % of all childhood malignancies. EGFR mutations and congenital airway malformations have been identified as etiological factors in the development of precancerous lesions that eventually progress to malignancy. The availability of genome sequencing and advanced imaging has made it possible to associate primary lung adenocarcinoma with mutations and structural malformations. Early diagnosis with the help of these techniques may result in surgical resection during early stages of the disease and possibly provide definitive treatment. Development of lung adenocarcinoma in pediatric patients in the absence of the above factors has been recorded anecdotally. It is possible that these patients may harbor a yet unknown set of mutations and recording this cases and preserving their tissues is of vital importance in the detection of these yet unknown etiologies.     

microRNAs in cancer management

Since the identification of microRNAs (miRNAs) in 1993, and the subsequent discovery of their highly conserved nature in 2000, the amount of research into their function--particularly how they contribute to malignancy--has greatly increased. This class of small RNA molecules control gene expression and provide a previously unknown control mechanism for protein synthesis. As such, it is unsurprising that miRNAs are now known to play an essential part in malignancy, functioning as tumour suppressors and oncogenes. This Review summarises the present understanding of how miRNAs operate at the molecular level; how their dysregulation is a crucial part of tumour formation, maintenance, and metastasis; how they can be used as biomarkers for disease type and grade; and how miRNA-based treatments could be used for diverse types of malignancies.     

Secondary non-hematopoietic cancers arising following treatment of hematopoietic disorders

Aggressive treatment of neoplastic disease has resulted in improved survival and, in some cases, cure of the primary malignancy. One of the most serious complications of such anticancer treatment has been the occurrence of an acute leukemia (primarily non-lymphocytic) several years after the successful treatment of the original neoplasm. Within the last 12 years, the authors have encountered 26 individuals who developed a second non-hematopoietic malignancy (excluding skin cancers) following primary aggressive treatment of a hematopoietic malignancy. All individuals had been treated with chemotherapy (24 of 26 with alkylating agents). The secondary tumors included lung (7), colon (6), gastric (4), bladder (3), esophageal (3), rectal (2) and pancreatic (1) tumors. The average time to development of the second malignancy in this series was 55.1 months, and the survival period following the diagnosis of the second malignancy averaged 7.3 months. It may be that aggressive anticancer treatment may be responsible for the emergence of a host of second non-hematopoietic carcinomas in addition to the now well established association with induced acute non-lymphocytic leukemias.     

Soft tissue tumours of the retroperitoneum

Purpose. This review summarizes the more prevalent soft tissue tumours arising in the retroperitoneum and highlights some recent fundamental and diagnostic developments relevant to mesenchymal tumours.Discussion. The retroperitoneum is an underestimated site for benign and malignant neoplastic disease, and represents the second most common site of origin of primary malignant soft tissue tumours (sarcomas) after the deep tissues of the lower extremity. In contrast to the predominance of benign soft tissue lesions over malignant sarcomas elsewhere, retroperitoneal mesenchymal lesions are far more likely to be malignant. The differential diagnosis is primarily with the more common lymphoproliferative and parenchymatous epithelial lesions arising in this area, and with metastatic disease from known or unknown primary sites elsewhere.The most prevalent mesenchymal tumours at this site are of a lipomatous, myogenic or neural nature.Their generally late clinical presentation and poorly accessible location provides numerous clinical challenges; optimal radiological imaging and a properly performed biopsy are essential cogs in the management route. Histopathological diagnosis may be complicated, but has been aided by developments in the fields of immunohistochemistry and tumour (cyto)genetics. Despite significant advances in oncological management protocols, the prognosis remains generally less favourable than for similar tumours at more accessible sites.     

FDG-PET and detection of distant metastases and simultaneous tumors in head and neck squamous cell carcinoma: a comparison with chest radiography and chest CT

Detection of distant metastases and second primary tumors in patients with head and neck squamous cell carcinoma (HNSCC) is of importance because of the impact on treatment and prognosis. The aim of this study was to assess the value of whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) in detecting distant metastases and second primary tumors below clavicular level in HNSCC compared to chest CT and chest radiography (CXR). Patient records of 149 consecutive patients with a primary HNSCC in whom a whole-body FDG-PET for initial staging was performed were reviewed. FDG-PET showed a sensitivity and specificity for detecting distant disease of 92% and 93%, respectively. Chest CT (n=82) showed a sensitivity and a specificity of 74% and 61% respectively. CXR (n=106) showed a sensitivity and a specificity of 41% and 91%, respectively. FDG-PET was shown to be able to detect distant metastases and second primary tumors in HNSCC with a high sensitivity and specificity. The higher sensitivity of PET compared to chest CT is mainly due to the detection of extrapulmonary malignancy. Sensitivity of PET and CT were similar in detecting intrapulmonary malignancy, but PET specificity was significantly higher. FDG-PET helps to determine the nature of pulmonary lesions and might be considered as a first diagnostic modality for detecting distant disease in advanced HNSCC.     

Colon cancer with isolated metastasis to the kidney at the time of initial diagnosis

Blood-borne metastases to the kidneys from solid tumors have received little attention in the medical literature because they usually occur in a setting of advanced systemic disease, and renal involvement is a elatively minor cause of symptoms. Although the frequency of metastases to the kidney in cancer patients is 7–13% in large autopsy series, incidental discovery of a renal metastasis as the first manifestation of a primary tumor is a very rare event. The most common primary malignancy to involve the kidney is bronchogenic carcinoma, followed by breast and gastrointestinal cancers. In this article, we report a patient with left colon cancer and isolated metastasis to the right kidney at the time of initial diagnosis. Left hemicolectomy and right nephrectomy were performed. Adjuvant systemic chemotherapy consisting of 5-fluorouracil (5-FU) and folinic acid (FA) was given. 5-FU and FA were stopped after four cycles because metastases to the lung and liver occurred about 3 mo after the surgery during adjuvant chemotherapy. Capecitabine was started. The patient died 9 mo after the discovery of the isolated renal metastasis. Nephrectomy is more for diagnostic clarification in the setting of synchronous primary because it has no effect on survival and its effect on quality of life is minimal; as seen in our case, the other organ metastases rapidly occur and the survival is limited. Nephrectomy may also compromise the choice of chemotherapy agents that require renal clearance, thus a careful evaluation of renal functions is necessary if a nephrectomy is performed. In the matter of a decreased renal clearance, the doses of these drugs should be decreased or the choice should be reevaluated.     

Carcinoma of unknown primary (CUP-Syndrom)

The diagnosis of cancer is not necessarily linked to the identification of the primary malignancy. Clinicians treating patients with carcinoma of unknown primary (CUP) are often facing diagnostic and therapeutic difficulties. Foremost, there is no generally accepted definition of CUP-syndromes. One of the most striking features of this type of cancer is an atypical pattern of metastases associated with an unusual growth behavior. After detection of metastatic disease without a corresponding primary tumor, limited diagnostic effort should focus on potential therapeutic strategies. First of all, potentially curative tumor types (e. g. extragonadal germ cell cancer, atypical malignant lymphoma), or at least potentially chemo-sensitive cancers should be recognized and adequately treated. Otherwise, various treatment options like surgery, radiotherapy and other medical strategies should be considered. However, the vast majority of patients with CUP-syndrome have a poor prognosis with a median survival time of 3–11 months. Population-based analyses showed that only 15% of all patients with CUP-syndrome survive the first year after diagnosis.     

Primary papillary thyroid carcinoma previously treated incompletely with radiofrequency ablation

Radiofrequency ablation (RFA) recently has been applied to benign thyroid nodules, mainly for the cosmetic reasons, and limited cases of local recurrences or focal distant metastases of well-differentiated thyroid cancer, in the high-risk reoperative condition or for the palliative purpose. But no report has been made on the RFA for primary thyroid cancer to date. We report on a patient with primary papillary carcinoma of thyroid gland who had undergone RFA before the cytological diagnosis of malignancy, later referred and treated with robotic surgery successfully. We can learn the following lessons from our case; (1) the RFA for operable primary thyroid malignancy should be avoided, because of the possibility of remnant viable cancer and undetectable nodal metastasis, and (2) robotic or endoscopic thyroid surgery may be a feasible operative method for benign or malignant thyroid nodules previously treated with RFA.     

Lung Cancer Presenting as a Soft-Tissue Metastasis

Soft-tissue metastasis refers to the growth of cancer cells, originating from internal cancer, in soft tissues. In most cases, soft-tissue metastases develop after initial diagnosis of the primary internal malignancy and late in the course of the disease. In very rare cases, they may occur at the same time or before the primary cancer has been detected. In our cases, the soft-tissue metastases and the primary lung cancer were diagnosed at the same time.Key Words: Lung cancer, Soft-tissue metastasis, Non-small-cell carcinoma, Computed tomography, Positron emission tomography, Magnetic resonance imaging     

A Huge Renal Cell Carcinoma, Nine Years after Its Primary Diagnosis and Obligate Observation

The clinical diagnosis of renal cell carcinoma (RCC) is radiographic. Effective imaging of the kidneys can be achieved by ultrasound, CT or MRI [Chawla et al.: J Urol 2006;175:425-431]. Solid lesions detected by ultrasound and those showing enhancement on cross-sectional imaging are considered malignant until proven otherwise. The standard of care for clinically localized RCC remains surgical resection due to the favorable prognosis associated with surgery and the relative ineffectiveness of systemic therapy. Since patients with localized RCC are often symptom-free, they sometimes refuse to receive surgical treatment or are left untreated based on a diagnosis of benign lesions. There are also cases where an RCC is relatively large and causes symptoms but is not treated surgically because of complications and other reasons. We report a 54-year-old male who underwent a difficult radical nephrectomy 9 years after the primary RCC malignancy diagnosis.