Manifestation Of Metastatic Disease Research Articles

Perimandibularna metastaza karcinoma rektuma - prikaz slučaja

Introduction. Colorectal cancer is the third most common cancer and metastatic disease is an important and frequent clinical problem. Metastases in the oral and maxillofacial region are rare, comprising 1-2% of all malignant lesions, and clinically resemble common benign conditions. Case report. A 59-year-old woman diagnosed with rectal cancer developed perimandibular lesion as a first sign of metastatic process. Metastasis manifested clinically during the curative intent treatment of rectal cancer (preoperative chemo-irradiation) as a rapidly growing tumefaction close to the mandible angle. After the biopsy and histopathological examination of the lesion that clinically resembled abscess, metastasis of rectal cancer was diagnosed. Incidentally, a cerebral metastasis was diagnosed as well. Although it was oligometastatic rectal cancer, surgical treatment was not indicated due to extensive infiltrative characteristics of the perimandibular lesion. The patient was treated with chemotherapy, with good clinical response. Biological therapy was not available at that moment. Cerebral metastasis was treated with stereotactic neuroradiosurgery with gamma knife. Unfortunately, the patient died from cerebrovascular insult. Conclusion. Lesions in the oral and maxillofacial region may be the first manifestation of metastatic disease. Since early diagnosis of metastatic process has prognostic implications, any new formation in the oral and maxillofacial region in a patient with colorectal cancer requires cautious observation and histological examination.

Abstract A31: Tracking the evolution of soft tissue sarcoma and GIST using liquid biopsies

Abstract Molecular analysis of circulating tumor DNA (ctDNA) has a large potential for clinical application by capturing mutations and heterogeneity through noninvasive sampling. The CircSarc studies aims to provide new insights into the clinical utility of liquid biopsies in soft tissue sarcomas (CircSarc STS) and gastrointestinal stromal tumors (CircSarc GIST). In CircSarc STS, we have enrolled 35 high-grade soft-tissue sarcoma patients with localized disease. Plasma from each patient has been collected longitudinally throughout the course of their disease, with a follow-up of up to 5 years. To identify patient-specific somatic mutations, the patients’ tumor and germline DNA have been exome sequenced. Somatic mutations in cfDNA are being identified using ultra-low-pass WGS or targeted NGS. At time of surgery and/or progression, we detect ctDNA in 30% of the first soft-tissue sarcoma samples with higher levels in larger or metastatic tumors. In a proof-of-concept study, we have shown that that levels of tumor-specific mutations in plasma correlated to clinical manifestation of metastatic disease. In CircSarc GIST, plasma has been collected for a cohort of 30 metastatic GISTs and at time of diagnosis for 50 GISTs. Somatic mutations in the tumor have been determined by targeted sequencing or whole-exome sequencing. Somatic mutations in ctDNA are identified using targeted NGS. The levels of somatic mutations in ctDNA are being correlated with clinicopathologic features. ctDNA was detected in 36% of treatment-naïve GIST patients, including all patients with metastatic disease, and the tumor burden was the most important detection determinant. Analysis of metastatic GISTs is ongoing, but repeated plasma samples in a progressing patient have demonstrated that clonal evolution can be monitored over time. ctDNA analysis of the patient revealed multiple resistance mutations, and these were spatially distributed in the primary tumor. Our work shows that detection of mutations in plasma is particularly feasible for patients with high tumor burden. Mutational analysis by use of liquid biopsies can capture the molecular heterogeneity of the tumor and guide treatment decisions during progression. Citation Format: Heidi M. Namløs, Kjetil Boye, Seyed H Moosavi, Daniel Vodak, Nitin Sharma, Susanne Lorenz, Bodil Bjerkehagen, Stine Næss, Eivind Hovig, Nina Jebsen, Anders Ståhlberg, Ola Myklebost, Leonardo A. Meza-Zepeda. Tracking the evolution of soft tissue sarcoma and GIST using liquid biopsies [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A31.

Metastatic Liposarcoma: A Case of Partial Remission with Eribulin in Late Treatment Lines

Liposarcoma, a type of soft tissue sarcoma, represents a therapeutic challenge, in particular in the metastatic setting. This case describes a patient with retroperitoneal liposarcoma that was first treated by surgery and, upon manifestation of metastatic disease, with a series of chemotherapy regimens comprising doxorubicin (line 1), doxorubicin plus ifosfamide (line 2), trabectedin (lines 3 and 4) and dacarbazine (line 5). While transient partial remission was achieved in the first three lines, rapid disease progression was observed in subsequent therapies. After failure of the previous chemotherapy regimens, eribulin was administered (line 6), and partial remission was achieved within five months. However, the occurrence of grade 3 polyneuropathy led to temporary discontinuation of therapy. Overall, metastatic liposarcoma was controlled for twelve months with eribulin treatment in a heavily pre-treated patient. This case underscores the efficacy of eribulin in treatment-refractory advanced/metastatic liposarcoma.

Abstract IA05: Selective pressure by activated T cells identifies de novo and adaptive resistance mechanisms in melanoma

Abstract Melanoma has been the tumor type in which immune checkpoint antibodies have been directed for the longest time in clinical trials and clinical practice. Compared to many other advanced solid tumors, a significant minority of patients have manifestations of metastatic disease that are amenable to minimally invasive biopsies to fuel translational research. With CTLA-4 blocking antibodies, the response rate was only 10% and insights into predictive biomarkers only began to emerge once large numbers of patients had been treated and with long-term follow-up. However, with PD-1/PD-L1 blocking antibodies response rates as high as 40% have been observed in previously untreated melanoma patients, making it far more tractable to glean insights into differences between responders and nonresponders in smaller number of patients. Emerging data from analysis of pretreatment tumor biopsies strongly support the greater, but still not high, likelihood of patients responding to PD-1/PD-L1 antibody-based therapy if there are robust numbers of CD8+ T cells infiltrating into a tumor prior to the start of therapy. Response prediction appears to be improved by assessment of T-cell infiltration into tumors early in the course of therapy. Modest improvement in response prediction appears to be achieved by accounting for the presence of regulatory T cells, with those tumors having the highest effector CD8+/Treg ratio being the most likely to respond. Additional predictive accuracy is contributed by a marker of T-cell activation, such as granzyme B, which would only be scored as positive if there are T cells present in the first place. While many additional modulators of T-cell entry and function have been implicated as mechanistically related to immune checkpoint antibody efficacy/resistance, none have been shown to have add predictive accuracy for response. A parallel body of evidence has developed indicating that the presence of predicted mutated neoantigens can predict response to immune checkpoint antibodies in melanoma. It is notable that melanoma has the highest number of mutations per megabase of any common solid tumor, which is thought to associate with the high response rate (40%) compared to other cancers in which PD-1/PD-L1 antibodies have demonstrated efficacy leading to regulatory approvals (15-20% response rates). The current state-of-the-art approach for predicting the presence of mutated antigens is algorithm-based, matching altered peptide sequences with a patient's HLA type to rank potential high-affinity binders. A very small number of such antigens have been validated by the presence of specific T-cell clones that recognize those antigens in patients. Nonetheless, response prediction appears robust and roughly compared to that achieved with phenotypic markers of tumor recognition described above, particularly when predicted mutated neoantigens are clonal. The most recent area of active investigation pertains to the phenotype of tumors with de novo resistance to immune checkpoint antibodies and mechanisms of acquire resistance. Early work suggests that the same phenotype of resistance associated with MAP kinase pathway targeted therapy (tumor cells that lose expression of melanocyte markers in favor of neural crest markers) predicts nonresponse to PD-1 antibodies. Very few patients with progression following response have been interrogated to date, but genetic loss of components of the MHC complex and inactivating mutations in the interferon signaling pathway in tumor cells appear to account for a significant proportion of cases. Citation Format: Keith T. Flaherty. Selective pressure by activated T cells identifies de novo and adaptive resistance mechanisms in melanoma [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr IA05.

Abstract 5700: CircSarc: Disease monitoring by liquid biopsies in sarcomas

Abstract The CircSarc study aims to provide new insights into the clinical utility of liquid biopsies in soft tissue sarcomas. At present, mutational profiles of solid tumours are obtained from tissue biopsies or surgical specimens. Recent advances in technology now allows to use blood plasma as a “liquid biopsy”, examining circulating tumour DNA (ctDNA) shed by the tumour cells into peripheral blood. ctDNA in plasma carries tumour-specific alterations that can be used to monitor minimal residual disease, response to therapy, tumour burden and evolution throughout the course of the disease. In CircSarc, we have enrolled 30 high-grade soft tissue sarcoma patients, with localised disease, that are being followed throughout the course of their disease. Plasma from each patient is collected longitudinally; before and after surgery, at each routine control and before and after each treatment cycle. Patient’s tumour and germline DNA were exome sequenced to identify tumour-specific mutations, and ctDNA is being sequenced using a comprehensive 900 cancer gene panel. The level of ctDNA in plasma, represented by the tumour-specific biomarkers, are then monitored throughout the course of the treatment, and acts as an indicator of tumour burden. In addition, we are analysing plasma samples from 70 Gastro Intestinal Stroma Tumour samples using targeted resequencing with Anchored Multiplex PCR. The levels of KIT and PDGFRA mutations in ctDNA are being correlated with clinical and pathological features. The established targeted resequencing protocols for ctDNA provide different levels of complexity and sensitivity. In the first screening, we have successfully detected somatic mutations in plasma at time of surgery in 70% of the samples analysed. Mutations present in the tumour at an allele frequency large than 20% can be robustly identified in plasma. In addition, analysis of plasma samples identified novel mutations not detected in the primary tumour, possibly reflecting intra-tumour heterogeneity. These mutations are being followed throughout the course of the disease to monitor tumour evolution and resistance. In a proof-of-concept study, we have shown that that levels of tumour-specific mutations in liquid biopsies correlated to clinical manifestation of metastatic disease in aggressive sarcoma, and have the potential to detect disease progression at an early stage. Our work provides new insights into the clinical significance of ctDNA in sarcomas. By repeated sampling of liquid biopsies, somatic mutations identified in ctDNA can be used as unique non-invasive tumour-specific biomarkers for monitoring tumour burden and disease evolution throughout the course of the disease. Citation Format: Heidi M. Namløs, Seyed Hossein Moosavi, Bodil Bjerkehagen, Olga Zaikova, Synnøve Granlien, Stine Næss, Nina Louise Jebsen, Skyler Mishkin, Eva W. Stratford, Else Munthe, Kirsten S. Hall, Lars B. Aasheim, Eivind Hovig, Brian Kudlow, Ola Myklebost, Kjetil Boye, Leonardo A. Meza-Zepeda. CircSarc: Disease monitoring by liquid biopsies in sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5700. doi:10.1158/1538-7445.AM2017-5700

Use of liquid biopsies to monitor disease progression in a sarcoma patient: a case report

BackgroundMany patients experience local recurrence or metastases after receiving potentially curative treatment, and early detection of these events is important for disease control. Recent technological advances make it possible to use blood plasma containing circulating cell-free tumour DNA (ctDNA) as a liquid biopsy. In this case report we show how serial liquid biopsies can be used to monitor the disease course and detect disease recurrence in a sarcoma patient.Case presentationA 55-year-old male presented with a rapidly growing, painful palpable mass in the left groin region, and a biopsy revealed a high-grade malignant spindle cell sarcoma. No metastases were detected on radiologic imaging scans. Using targeted resequencing with a custom 900 cancer gene panel, eight somatic mutations among them KRAS and NF1, were identified in the primary tumour. Targeted resequencing of plasma cell-free DNA (ctDNA) collected before and after surgery and at disease progression confirmed the presence of six of eight mutations at all three time points. The ctDNA level, estimated from the somatic allele frequencies of these six mutations, was high in plasma taken at the time of surgery, at levels similar to the primary tumour. Detection of low levels of ctDNA three days after surgery indicated persistent microscopic disease. Repeated radiologic imaging six weeks postoperatively showed widespread metastatic disease in the lungs, skeleton and the pelvic region. At this time point there was a dramatic increase in the ctDNA level, reflecting the disease progression of the patient. The patient had an unusually aggressive cancer, and succumbed to the disease 13 weeks after surgery.ConclusionsThis case report demonstrated that targeted resequencing of ctDNA from longitudinal collected plasma can be used to monitor disease progression in a soft tissue sarcoma patient, including manifestation of metastatic disease. The ctDNA represented the genomic profile of the tumour, supporting clinical use of liquid biopsies to identify tumour-specific mutations as well as recurrent disease.

Ocular symptoms as primary manifestation of metastatic disease

Metastases to the eye are rare and frequently intra-ocular. Most metastases occur from tumors in the gastrointestinal tract, breast or the lungs. Very rarely an eye disease is the primary manifestation in such cases. We report 3 such cases of unusual metastases to eye where ocular symptoms were primary clinical manifestations an unknown primary.

Sister mary joseph′s nodule: What lies beneath?

Dear Editor, We recently had a 79-year-old male with no significant medical history who was referred to our hospital for a pulmonary embolism. During examination a 5 cm × 5 cm fungating mass was discovered on his belly [Figure 1]. Patient reported that the mass has been present for months and gradually increasing in size. A computed tomography scan of chest, abdomen and pelvis revealed no other abnormality. The biopsy of mass revealed moderately differentiated adenocarcinoma with stain consistent with tumor of lower gastrointestinal tract. A colonoscopy confirmed adenocarcinoma of transverse colon. Figure 1 A 5 cm ×5 cm fungating mass on patient's periumbilical area This rare manifestation of metastatic disease was recognized by a surgical assistant of Dr. William Mayo, Sister Mary Joseph, whose name has since been used to explain these umbilical nodules.[1] These metastatic lesions are mostly from gastrointestinal (52%) and gynecological neoplasms (28%), most commonly from the stomach (23%), colon (15%), pancreas (10%), and ovary (16%), and less frequently from the uterus, cervix, gallbladder, and small intestine.[2] Metastatic lesions can reach the umbilicus via spread through lymphatic ducts, the venous network, arterial spread, contiguous extension, or even through iatrogenic seeding with laparoscopy. These different pathways may help explain why there is such a wide group of malignant tumors that can produce these nodules.[3] The presence of these lesions is often a poor prognostic factor, as these patients have advanced metastatic disease at the time of initial diagnosis. In several studies, the average survival after the appearance of these nodules was approximately 10-11 months.[4] Sister Mary Joseph nodule is a rare first manifestation of colon cancer. Physicians should be aware of this unusual presentation of colon cancer.

Sclerotic osseous metastases from renal cell carcinoma

This case series describes and illustrates three cases of sclerotic osseous metastases from untreated renal cell carcinoma (RCC). RCC is commonly metastatic to the skeleton but almost always produces lytic metastases, with only three prior reports of sclerotic metastases identified in the literature. Sclerotic metastasis causing low back pain was the initial disease presentation in two of the three patients in this case series and the first manifestation of metastatic disease in one. The most common metastatic sites of RCC, i.e., retroperitoneal lymph nodes, lung, and liver, were not identified in any of the cases, and skeletal involvement with epidural extension was the only site of metastasis in two. Pathologic specimens from all three cases revealed RCC of high nuclear grade.

Cutaneous malignant melanoma in an 11-month-old Russian blue cat

CASE HISTORY: A grey mass developed on the tail base of an 11-month-old Russian blue cat. The mass grew slowly for 2 months and then became ulcerated. CLINICAL FINDINGS: The mass was excised, and histology revealed it to be a malignant melanoma. Skin adjacent to the melanoma and underlying tissue contained large aggregates of melanin and numerous melanophages. Seven months later, an additional malignant melanoma was excised from the skin on the left thorax. Three months after the second melanoma was excised, the left axillary lymph nodes were enlarged; four were excised, and found to contain metastases. The cat became lethargic and anorexic, and was subject to euthanasia at 26 months of age. Post-mortem examination revealed numerous small well-circumscribed melanomas scattered within the S/C tissue overlying the left thorax and within the left axilla. These were interpreted to be in-transit metastases. Metastatic foci were also visible within the spleen, liver, lungs, lymph nodes and a rib; numerous small melanomas were also present throughout the mesentery. DIAGNOSIS: Cutaneous malignant melanoma with numerous distant and in-transit metastases. CLINICAL RELEVANCE: Although cutaneous malignant melanomas appear to be rare in young cats, they can display a similar clinical behaviour to malignant melanomas in humans, and a guarded prognosis should be suggested for neoplasms of this type. In humans, in-transit metastases are a well-recognised consequence of removing lymph nodes that drain areas containing neoplastic disease. This manifestation of metastatic disease has not previously been reported in the veterinary literature.

Abstract 4219: Biomarkers of cancer stem cells and invasion can predict breast cancer metastasis

Abstract Background: Breast cancer mortality is largely attributable to the development of systemic, hematogenous metastatic disease. Although nearly 10-15% of patients have an aggressive form disease that metastasizes within three years after initial diagnosis, the clinical manifestations of metastatic disease can appear ten or more years later. To decrease the risk for the emergence of metastatic tumors, nearly 80% of the patients are treated with adjuvant chemotherapy. The clinical benefit is a 3-10% increase in 15-yr survival, depending upon patient age at diagnosis. Currently established prognostic criteria such as the histopathological grade of the tumor or tumor size do not successfully predict systemic metastatic potential. An enrichment of cancer stem cells in the primary tumor has been shown to be a poor prognostic marker in patients. Epithelial to Mesenchymal Transition (EMT) in breast cancer cells have been shown to give rise to cells that have cancer stem cell like properties. Both of these cells types have been shown to be highly invasive. We have identified invasion markers that can predict EMT, drug and radio resistance in breast cancer cells. In this study we are using biomarkers for cancer stem cells (CD44+/CD24−) and markers of invasion (Mena/Mena11a) to identify cancer initiating cells in Fine Needle Aspiration (FNA). We correlate these ratios with a microanatomical structure called Tumor Microenvironment of Metastasis (TMEM) comprising of a direct apposition of an endothelial cell, a cancer cell and a stromal macrophage in the breast cancer tissue. TMEM has been previously reported to strongly correlate with metastasis. Hypothesis: The percentage of CD44+/CD24− expression can be used to estimate the number of cancer stem cells in FNA samples. The ratio of Mena to Mena11a protein can be used as a measurement of tumor cell response to the microenvironment and its metastatic phenotype. Measuring the stem cell biomarkers and Mena isoforms in cells collected by FNA biopsy using FACS and combining that with the assessment of TMEM density we will be able to develop a simple, quick and inexpensive method of determining metastatic potential of an individual tumor. Methods: FNA was conducted on lumpectomy or mastectomy tissues using fine needles, quality of FNA determined by smear staining. Cells were enzymatically digested, fixed and permeabilized. They were then be subjected to flowcytometry analysis using antibodies against stem cell and invasion markers. Rest of the tumor was processed for histopathology and TMEM analysis. Statistical analysis was performed to identify correlation. Results: Our initial results show that there is a strong correlation between CD44+/CD24− cells in the FNA with TMEM scores. We also report a very high correlation with can also be predicted by the ratios of different splice variants of Mena. This method can be easily used in the clinical setting and applied to a number of different biomarkers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4219.

Models Support Prophylactic Cranial Irradiation

Models Support Prophylactic Cranial Irradiation

Intramedullary spinal cord metastasis of lung adenocarcinoma presenting as brown-sequard syndrome

Background It is extremely rare for cancer to present first as an intramedullary spinal cord metastasis. Furthermore, because it is unlikely for spinal cord neoplasm to present acutely, an acute presentation may signify metastatic disease and should be considered in the initial differential diagnosis. Methods The authors present a case of a 59-year-old man presenting with Brown-Sequard syndrome and in whom metastatic lung adenocarcinoma to the spinal cord was subsequently discovered. Review of the literature reveals this case to be one of only a very few where intramedullary tumor was the first manifestation of metastatic disease. Results The mainstay of treatment for intramedullary spinal metastases remains steroids, radiation, and chemotherapy, though no well-designed study compares these modalities by long-term survival and functional results. This patient underwent local radiation and systemic chemotherapy following surgical resection. Conclusions This patient had no preoperative signs suggesting disease in other organs, making the diagnosis of lung adenocarcinoma metastatic to the intramedullary cord surprising, especially given the extremely rare incidence of spinal intramedullary metastatic disease. However, the patient had an acute presentation, uncommon for primary neoplasm, which may be an indication of metastatic disease.

A case of Tumoral 'Pneumonia' Caused by Prostatic Adenocarcinoma

The lung is one of the most frequent sites of metastasis for extrathoracic tumors. Certain malignancies show a particular tendency to metastasize to lung, and in 15 to 25% of these cases, lung involvement is the only manifestation of metastatic disease. The most common presentation is the form of multiple bilateral nodules or masses of varying sizes. Lymphangitic metastasis is comprising 6 to 8% of all pulmonary metastasis. A striking variant of parenchymal involvement occures when dyscohesive tumor cells fill alveoli to produce a tumoral pneumonia. Carcinomatous lymphangitis of prostate origin is infrequent and usually carries a poor prognosis, and tumoral pneumonia of it is extremely rare. We report herein a case of prostate carcinoma metastasizing to lung, simulates atypical pneumonia, and disclosed by acute chest illness.

Tumor fever in patients with nasopharyngeal carcinoma: clinical experience of 67 patients.

From 1982 through 1996, 67 patients with nasopharyngeal carcinoma (NPC) proven to have tumor fever (TF) were analyzed. All were in metastatic stage when TF occurred. Forty-five patients (67%) had recurrent disease. Thirty-eight (57%) had fever before metastatic lesions were detected. The metastatic sites were: 84% in bone, 69% in liver, and 19% in lung. Multiple-organ metastases were found in 64% of the patients. Nine patients (13%) had bone-marrow invasion. When TF was present, 22 (33%) patients had other paraneoplastic syndromes, of which leukemoid reaction (LR) was seen most frequently. After the initiation of naproxen or indomethacin, most patients had complete lysis of the fever within 48 hours. Of the six patients receiving chemotherapy as the initial therapy, all of their temperatures returned to normal range after the treatment. Some patients, particularly those with tumor progression, developed TF again when antipyretic drugs were discontinued. The median survival time was 5 months. In conclusion, TF in NPC is usually a manifestation of metastatic disease. Tumor fever often associates with other paraneoplastic syndromes. Naproxen, indomethacin, and systemic chemotherapy all had effectiveness in ameliorating TF. Systemic metastases should be suspected in NPC patients with fever of unknown origin.

Typical and Atypical Presentations of Testicular Carcinoma

Testicular carcinoma most commonly presents as a testicular mass. Approxiately 10-15% of patients, however, present with manifestations of metastatic disease. The reported clinical presentations of metastatic testicular carcinoma are varied and include abdominal mass, hemoptysis, adenopathy, respiratory difficulty, anorexia, nausea, vomiting, lumbar back pain, and lower extremity swelling. A comprehensive review of the literature indicated that testicular carcinoma presents as a testicular abnormality 90% of the time. In 10% of cases, however, the patients will present with nontesticular manifestations of metastatic disease. The authors provide a summary of reported nontesticular presentations of testis cancer and describe a unique case wherein the clinical presentation was spontaneous ejaculatory failure.

Intracardiac mass as the initial manifestation of metastatic germ cell tumor

Cardiac metastases as initial presentation of disseminated germ cell tumors have rarely been reported. The hematogenous route is believed to be the most common pattern of dissemination by germ cell tumour, mainly to the lung, central nervous system and liver. We report a 33-year-old patient with embryonal cell carcinoma who presented with an intraatrial metastatic mass as the initial manifestation of metastatic disease.

Significance of local recurrence after mastectomy for breast cancer

In a retrospective study 678 patients who underwent (modified) radical mastectomy between 1970 and 1986 were analysed. By comparing the groups of patients who experienced local recurrence, regional recurrence or distant metastasis during follow-up with patients who remained free of disease, we have tried to gain some insight into the significance of local recurrence. By looking at the prognostic factors and the disease-free period there is hardly any difference between the patients with either a local, regional or distant recurrence. Actuarial survival of patients with local recurrence is slightly better than the survival of patients with distant metastasis ( P = 0.009). From our results and from the literature we conclude that an isolated local recurrence after mastectomy for breast cancer is, in most cases, a first manifestation of metastatic disease. Probably only a minority of the local recurrences is caused by tumour cells left behind in the operation field.

‘Cold Lesions’ on Bone Scan A Case of Metastatic Squamous Cell Carcinoma of the Penis

Photopenic osseous lesions are a well-recognized but unusual manifestation of metastatic disease on bone scintigraphy. Common primary tumors giving rise to such lesions include lung, breast, renal, and thyroid. This case report illustrates multiple "cold" osseous metastases from aggressive penile squamous cell carcinoma without radiographic destruction.

Cystic pulmonary metastatic sarcoma

Neoplastic cavitary lesions are an unusual type of pulmonary metastases. The authors report two cases of cystic metastatic sarcoma of the lungs that illustrate the clinical, radiologic, and pathologic difficulties encountered in the diagnosis of these lesions. In one patient, multiple small, thin-walled cystic metastases from a lower leg leiomyosarcoma were the only manifestation of metastatic disease. The cystic lesions did not change over an 8-month period and a diagnosis of malignancy was not established until spontaneous pneumothorax, presumably due to rupture of the malignant blebs, prompted a thoracotomy. In the second patient, three thin-walled bullae developed after treatment of noncystic pulmonary metastases from a lower-leg synovial sarcoma. In both patients, the cystic lesions were not evident on chest radiographs, but were well visualized with computed tomography (CT), where they mimicked benign bullous disease. However, additional small cavitary lesions not seen with CT were present in resected pulmonary wedge specimens from both patients. A great degree of variability in the cellular composition of the cyst wall lining in both cases, and a lack of any solid neoplastic tissue masses in one case, led to histopathologic difficulties that required immunohistochemical studies for definitive diagnosis of the metastatic disease. These cases show that pulmonary bullae, even though thin-walled and benign-appearing on CT, may be a manifestation of pulmonary metastases. These lesions must therefore be surgically removed from patients in whom a curative resection of pulmonary metastases is warranted.