Shrinkage versus fragmentation response in neoadjuvantly treated oesophageal adenocarcinoma: significant prognostic relevance.

AIMS: No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival. METHODS AND RESULTS: Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper-gastrointestinal (GI) centres (2005-18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre-defined three-step flowchart. The results were validated in an external cohort (2001-17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P < 0.001), less downstaging (48 versus 91%; P < 0.001), a higher risk of recurrence [risk ratio (RR) = 2.9, 95% confidence interval (CI) = 1.5-5.6] and poorer 5-year overall survival (30 versus 80% respectively, P = 0.001). CONCLUSIONS: The validation cohort confirmed these findings, although had more advanced cases (case-stages = III/IV 91 versus 73%, P = 0.005) and a higher prevalence of fragmented-pattern cases (80 versus 60%, P = 0.002). When combining the cohorts in multivariate analysis, the pattern of response was an independent prognostic factor [hazard ratio (HR) = 1.76, 95% CI = 1.0-3.0]. In conclusion, we established an externally validated, reproducible and clinically relevant classification of tumour response.

Computer-Aided Assessment of Melanocytic Lesions by Means of a Mitosis Algorithm.

An increasing number of pathology laboratories are now fully digitised, using whole slide imaging (WSI) for routine diagnostics. WSI paves the road to use artificial intelligence (AI) that will play an increasing role in computer-aided diagnosis (CAD). In melanocytic skin lesions, the presence of a dermal mitosis may be an important clue for an intermediate or a malignant lesion and may indicate worse prognosis. In this study a mitosis algorithm primarily developed for breast carcinoma is applied to melanocytic skin lesions. This study aimed to assess whether the algorithm could be used in diagnosing melanocytic lesions, and to study the added value in diagnosing melanocytic lesions in a practical setting. WSI's of a set of hematoxylin and eosin (H&E) stained slides of 99 melanocytic lesions (35 nevi, 4 intermediate melanocytic lesions, and 60 malignant melanomas, including 10 nevoid melanomas), for which a consensus diagnosis was reached by three academic pathologists, were subjected to a mitosis algorithm based on AI. Two academic and six general pathologists specialized in dermatopathology examined the WSI cases two times, first without mitosis annotations and after a washout period of at least 2 months with mitosis annotations based on the algorithm. The algorithm indicated true mitosis in lesional cells, i.e., melanocytes, and non-lesional cells, i.e., mainly keratinocytes and inflammatory cells. A high number of false positive mitosis was indicated as well, comprising melanin pigment, sebaceous glands nuclei, and spindle cell nuclei such as stromal cells and neuroid differentiated melanocytes. All but one pathologist reported more often a dermal mitosis with the mitosis algorithm, which on a regular basis, was incorrectly attributed to mitoses from mainly inflammatory cells. The overall concordance of the pathologists with the consensus diagnosis for all cases excluding nevoid melanoma (n = 89) appeared to be comparable with and without the use of AI (89% vs. 90%). However, the concordance increased by using AI in nevoid melanoma cases (n = 10) (75% vs. 68%). This study showed that in general cases, pathologists perform similarly with the aid of a mitosis algorithm developed primarily for breast cancer. In nevoid melanoma cases, pathologists perform better with the algorithm. From this study, it can be learned that pathologists need to be aware of potential pitfalls using CAD on H&E slides, e.g., misinterpreting dermal mitoses in non-melanotic cells.

USPIO-enhanced MRI of lymph nodes in rectal cancer: A node-to-node comparison with histopathology.

PURPOSE: To evaluate the initial results of predicting lymph node metastasis in rectal cancer patients detected in-vivo with USPIO-enhanced MRI at 3 T compared on a node-to-node basis with histopathology. METHODS: Ten rectal cancer patients of all clinical stages were prospectively included for an in-vivo 0.85 mm3 isotropic 3D MRI after infusion of Ferumoxtran-10. The surgical specimens were examined ex-vivo with an 0.29 mm3 isotropic MRI examination. Two radiologists evaluated in-vivo MR images with a classification scheme to predict lymph node status. Ex-vivo MRI was used for MR-guided pathology and served as a key link between in-vivo MRI and final histopathology for the node-to-node analysis. RESULTS: 138 lymph nodes were detected by reader 1 and 255 by reader 2 (p = 0.005) on in-vivo MRI with a median size of 2.6 and 2.4 mm, respectively. Lymph nodes were classified with substantial inter-reader agreement (κ = 0.73). Node-to-node comparison was possible for 55 lymph nodes (median size 3.2 mm; range 1.2-12.3), of which 6 were metastatic on pathology. Low true-positive rates (3/26, 11 % for both readers) and high true negative rates were achieved (14/17, 82 %; 19/22, 86 %). Pathological re-evaluations of 20 lymph nodes with high signal intensity on USPIO-enhanced MRI without lymph node metastases (false positives) did not reveal tumor metastasis but showed benign lymph node tissue with reactive follicles. CONCLUSIONS: High resolution MRI visualizes a large number of mesorectal lymph nodes. USPIO-enhanced MRI was not accurate for characterizing small benign versus small tumoral lymph nodes in rectal cancer patients. Suspicious nodes on in-vivo MRI occur as inflammatory as well as metastatic nodes.

Histological subtypes in triple negative breast cancer are associated with specific information on survival.

Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC. A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed. Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18-3.03; p = 0.008; OS HR 1.94; 95% CI 1.28-2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes. In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients.

Can Ex Vivo Magnetic Resonance Imaging of Rectal Cancer Specimens Improve the Mesorectal Lymph Node Yield for Pathological Examination?

PURPOSE: The aim of this study was to use 7 T ex vivo magnetic resonance imaging (MRI) scans to determine the size of lymph nodes (LNs) in total mesorectal excision (TME) specimens and to increase the pathological yield of LNs with MR-guided pathology. MATERIALS AND METHODS: Twenty-two fixated TME specimens containing adenocarcinoma were scanned on a 7 T preclinical MRI system with a T1-weighted 3-dimensional gradient echo sequence with frequency-selective lipid excitation (repetition time/echo time, 15/3 milliseconds; resolution, 0.293 mm) and a water-excited 3-dimensional multigradient echo (repetition time, 30 milliseconds; computed echo time, 6.2 milliseconds; resolution, 0.293 mm) pulse sequence.The first series of 11 TME specimens (S1) revealed the number and size of LNs on both ex vivo MRI and histopathology. The second series of 11 TME specimens (S2) was used to perform MR-guided pathology. The number, size, and percentages of yielded LNs of S1 and S2 were compared. RESULTS: In all specimens (22/22), a median number of 34 LNs (interquartile range, 26-34) was revealed on ex vivo MRI compared with 14 LNs (interquartile range, 7.5-21.5) on histopathology (P = 0.003). Mean size of all LNs did not differ between the 2 series (ex vivo MRI: 2.4 vs 2.5 mm, P = 0.267; pathology: 3.6 vs 3.5 mm, P = 0.653). The median percentages of harvested LNs compared with nodes visible on ex vivo MRI per specimen for both series were not significantly different (40% vs 43%, P = 0.718). By using a size threshold of greater than 2 mm, the percentage improved to 71% (S1) and to 78% (S2, P = 0.895). The median number of harvested LNs per specimen did not increase by performing MR-guided pathology (S1, 14 LNs; S2, 20 LNs; P = 0.532). CONCLUSIONS: Ex vivo MRI visualizes more LNs than (MR-guided) pathology is able to harvest. Current pathological examination was not further improved by MR guidance. The majority of LNs or LN-like structures visible on ex vivo MRI below 2 mm in size remain unexplained, which warrants a 3-dimensional approach for pathological reconstruction of specimens.

Validation of Whole-slide Digitally Imaged Melanocytic Lesions: Does Z-Stack Scanning Improve Diagnostic Accuracy?

BACKGROUND: Accurate diagnosis of melanocytic lesions is challenging, even for expert pathologists. Nowadays, whole-slide imaging (WSI) is used for routine clinical pathology diagnosis in several laboratories. One of the limitations of WSI, as it is most often used, is the lack of a multiplanar focusing option. In this study, we aim to establish the diagnostic accuracy of WSI for melanocytic lesions and investigate the potential accuracy increase of z-stack scanning. Z-stack enables pathologists to use a software focus adjustment, comparable to the fine-focus knob of a conventional light microscope. MATERIALS AND METHODS: Melanocytic lesions (n = 102) were selected from our pathology archives: 35 nevi, 5 spitzoid tumors of unknown malignant potential, and 62 malignant melanomas, including 10 nevoid melanomas. All slides were scanned at a magnification comparable to use of a ×40 objective, in z-stack mode. A ground truth diagnosis was established on the glass slides by four academic dermatopathologists with a special interest in the diagnosis of melanoma. Six nonacademic surgical pathologists subspecialized in dermatopathology examined the cases by WSI. RESULTS: An expert consensus diagnosis was achieved in 99 (97%) of cases. Concordance rates between surgical pathologists and the ground truth varied between 75% and 90%, excluding nevoid melanoma cases. Concordance rates of nevoid melanoma varied between 10% and 80%. Pathologists used the software focusing option in 7%-28% of cases, which in 1 case of nevoid melanoma resulted in correcting a misdiagnosis after finding a dermal mitosis. CONCLUSION: Diagnostic accuracy of melanocytic lesions based on glass slides and WSI is comparable with previous publications. A large variability in diagnostic accuracy of nevoid melanoma does exist. Our results show that z-stack scanning, in general, does not increase the diagnostic accuracy of melanocytic.

Whole-Slide Mitosis Detection in H&E Breast Histology Using PHH3 as a Reference to Train Distilled Stain-Invariant Convolutional Networks.

Manual counting of mitotic tumor cells in tissue sections constitutes one of the strongest prognostic markers for breast cancer. This procedure, however, is time-consuming and error-prone. We developed a method to automatically detect mitotic figures in breast cancer tissue sections based on convolutional neural networks (CNNs). Application of CNNs to hematoxylin and eosin (H&E) stained histological tissue sections is hampered by: (1) noisy and expensive reference standards established by pathologists, (2) lack of generalization due to staining variation across laboratories, and (3) high computational requirements needed to process gigapixel whole-slide images (WSIs). In this paper, we present a method to train and evaluate CNNs to specifically solve these issues in the context of mitosis detection in breast cancer WSIs. First, by combining image analysis of mitotic activity in phosphohistone-H3 (PHH3) restained slides and registration, we built a reference standard for mitosis detection in entire H&E WSIs requiring minimal manual annotation effort. Second, we designed a data augmentation strategy that creates diverse and realistic H&E stain variations by modifying the hematoxylin and eosin color channels directly. Using it during training combined with network ensembling resulted in a stain invariant mitosis detector. Third, we applied knowledge distillation to reduce the computational requirements of the mitosis detection ensemble with a negligible loss of performance. The system was trained in a single-center cohort and evaluated in an independent multicenter cohort from The Cancer Genome Atlas on the three tasks of the Tumor Proliferation Assessment Challenge (TUPAC). We obtained a performance within the top-3 best methods for most of the tasks of the challenge.

1399 H&E-stained sentinel lymph node sections of breast cancer patients: the CAMELYON dataset.

Background: The presence of lymph node metastases is one of the most important factors in breast cancer prognosis. The most common way to assess regional lymph node status is the sentinel lymph node procedure. The sentinel lymph node is the most likely lymph node to contain metastasized cancer cells and is excised, histopathologically processed, and examined by a pathologist. This tedious examination process is time-consuming and can lead to small metastases being missed. However, recent advances in whole-slide imaging and machine learning have opened an avenue for analysis of digitized lymph node sections with computer algorithms. For example, convolutional neural networks, a type of machine-learning algorithm, can be used to automatically detect cancer metastases in lymph nodes with high accuracy. To train machine-learning models, large, well-curated datasets are needed. Results: We released a dataset of 1,399 annotated whole-slide images (WSIs) of lymph nodes, both with and without metastases, in 3 terabytes of data in the context of the CAMELYON16 and CAMELYON17 Grand Challenges. Slides were collected from five medical centers to cover a broad range of image appearance and staining variations. Each WSI has a slide-level label indicating whether it contains no metastases, macro-metastases, micro-metastases, or isolated tumor cells. Furthermore, for 209 WSIs, detailed hand-drawn contours for all metastases are provided. Last, open-source software tools to visualize and interact with the data have been made available. Conclusions: A unique dataset of annotated, whole-slide digital histopathology images has been provided with high potential for re-use.

Does Nipple Discharge Color Predict (pre-) Malignant Breast Pathology?

Unilateral single-duct nipple discharge is associated with an increased risk for underlying breast malignancy. There is no consensus whether color of nipple discharge independently indicates the risk of malignancy. We sought to assess the relationship between the color of discharge and the risk of malignancy. Patients with unilateral single-duct nipple discharge without abnormalities on clinical and radiologic examination were included. Prior to diagnostic microdochectomy nipple discharge characteristics were registered. Multiple logistic regressions were performed to assess the relationship between color of nipple discharge and malignancy, corrected for age. During a mean follow-up period of 7.1 years we determined complication rate and false-negative rate of microdochectomy. A total of 184 patients were included (median age 53 years, range 19-84). Histologic examination revealed (in situ or invasive) breast carcinoma in 10.9% (20) of patients and high-risk lesions in 11.4% (21). Malignancy or high-risk lesions were found in 25% (OR: 1.37; 95% CI: 0.62-3.00) of patients with bloody discharge. Risk of underlying malignancy increased in patients >60 years (OR: 2.35; 95% CI: 1.14-4.83). Complication rate of microdochectomy was 2.7%. Single-duct, unilateral nipple discharge is a sign of underlying malignancy in a substantial proportion of cases. The majority of patients with unilateral single-duct nipple discharge, diagnosed with breast cancer, present with bloody discharge. However, the association between bloody nipple discharge and malignancy is not strong enough to distinguish high-risk patients. Therefore, invasive diagnostic procedures like microdochectomy should be offered to all patients with unilateral uniductal nipple discharge to search for underlying malignancy.

Propionibacterium acnes isolated from lymph nodes of patients with sarcoidosis.

Propionibacterium acnes has been repeatedly suggested as a candidate causative agent of sarcoidosis. It is the only microorganism that has been isolated from sarcoid lesions by bacterial culture so far and this has been described in Japanese patients only. We report two non-Japanese patients in whom mediastinoscopy was performed in order to obtain lymph node tissue for histopathology, which was suggestive for sarcoidosis. Bacterial culture of these uncontaminated mediastinal lymph nodes revealed P. acnes in both patients. As shown in these two cases, P. acnes can be isolated from sterile biopsied sarcoid lymph nodes of non-Japanese patients and supports the belief that there is an etiologic link between P. acnes sarcoidosis. Further elucidation could provide an opening to novel strategies using antibiotics for treating sarcoidosis.

Upregulation of IGF-1R expression during neoadjuvant therapy predicts poor outcome in breast cancer patients.

INTRODUCTION: The insulin-like growth factor 1 receptor (IGF-1R) may be involved in the development of resistance against conventional cancer treatment. The aim of this study was to assess whether IGF-1R expression of breast tumors changes during neoadjuvant therapy and to study whether these changes were associated with survival. METHODS: Paraffin embedded tumor tissue was collected from pretreatment biopsies and surgical resections of 62 breast cancer patients who were treated with neoadjuvant chemotherapy or endocrine therapy. IGF-1R expression was determined immunohistochemically and compared before and after treatment. RESULTS: High membranous IGF-1R expression at diagnosis correlated significantly with ER positivity, low tumor stage (stage I/II) and longer overall survival (p < 0.05). After neoadjuvant treatment, membranous IGF-1R expression remained the same in 41 (65%) tumors, was upregulated in 11 (18%) tumors and downregulated in 11 (18%) tumors. Changes in membranous IGF-1R expression were associated with overall survival (log-rank test: p = 0.013, multivariate cox-regression: p = 0.086). Mean overall survival time for upregulation, no change, and downregulation in IGF-1R expression was 3.0 ± 0.5 years, 7.3 ± 1.0 years and 15.0 ± 1.8 years, respectively. Changes in other parameters were not significantly associated with survival. CONCLUSION: Neoadjuvant therapy can induce changes in IGF-1R expression. Upregulation of IGF-1R expression after neoadjuvant treatment is a poor prognostic factor in breast cancer patients, providing a rationale for incorporating anti-IGF-1R drugs in the management of these patients.

Blinded double reading yields a higher programme sensitivity than non-blinded double reading at digital screening mammography: a prospected population based study in the south of The Netherlands.

PURPOSE: To prospectively determine the screening mammography outcome at blinded and non-blinded double reading in a biennial population based screening programme in the south of the Netherlands. METHODS: We included a consecutive series of 87,487 digital screening mammograms, obtained between July 2009 and July 2011. Screening mammograms were double read in either a blinded (2nd reader was not informed about the 1st reader's decision) or non-blinded fashion (2nd reader was informed about the 1st reader's decision). This reading strategy was alternated on a monthly basis. Women with discrepant readings between the two radiologists were always referred for further analysis. During 2 years follow-up, we collected the radiology reports, surgical correspondence and pathology reports of all referred women and interval breast cancers. RESULTS: Respectively 44,491 and 42,996 screens had been read either in a blinded or non-blinded fashion. Referral rate (3.3% versus 2.8%, p<0.001) and false positive rate (2.6% versus 2.2%, p=0.002) were significantly higher at blinded double reading whereas the cancer detection rate per 1000 screens (7.4 versus 6.5, p=0.14) and positive predictive value of referral (22% versus 23%, p=0.51) were comparable. Blinded double reading resulted in a significantly higher programme sensitivity (83% versus 76%, p=0.01). Per 1000 screened women, blinded double reading would yield 0.9 more screen detected cancers and 0.6 less interval cancers than non-blinded double reading, at the expense of 4.4 more recalls. CONCLUSION: We advocate the use of blinded double reading in order to achieve a better programme sensitivity, at the expense of an increased referral rate and false positive referral rate.

Germline MUTYH gene mutations are not frequently found in unselected patients with papillary breast carcinoma.

MUTYH-associated polyposis (MAP) is an autosomal recessive disease, which predisposes to polyposis and colorectal cancer. There is a trend towards an increased risk of breast cancer in MAP patients, with a remarkable proportion of papillary breast cancers. To determine whether MUTYH mutations are associated with this specific and rare type of breast cancer, 53 unselected patients with papillary breast cancer were analyzed for founder mutations in the MUTYH gene. No germline mutations were identified, indicating that biallelic MUTYH mutations are not a frequent underlying cause for the development of papillary carcinomas of the breast.

Is cytology useful in the diagnostic workup of male breast lesions? A retrospective study over a 16-year period and review of the recent literature.

OBJECTIVE: To determine the value of cytology in the workup of male breast lesions, important for the management in a same-day breast clinic. STUDY DESIGN: A total of 146 fine needle aspirations (FNAs) from the male breast were classified in the categories malignant, suspicious, atypical, benign and inadequate. Cytohistologic correlation was done. RESULTS: Histologic correlation was available in 85 cases. On FNA the 15 malignant cases were classified as malignant (n = 11), suspicious for malignancy (n = 2) or atypical (n = 2). Of the 35 benign lesions on histology 3 cases were classified as atypia and 1 as suspicious for malignancy on FNA. In the inadequate FNAs (n = 45), the corresponding histologic specimens were benign, no carcinomas were diagnosed. The sensitivity and specificity of the FNA compared to the definite resection diagnosis were 100% and 90.2%, respectively. The results were comparable with the outcomes of the reviewed studies on male breast lesions in the recent literature. CONCLUSION: Based on the nature of the benign breast lesions in man, a substantial number of inadequate FNAs were obtained. However, due to the good cytohistologic correlations in the group of malignant lesions, we can conclude that cytology remains an important diagnostic tool in the initial workup of male breast carcinomas.

More tumor-affected lymph nodes because of the sentinel lymph node procedure but no stage migration, because the 2002 TNM classifies small tumor deposits as pathologic N0 breast cancer.

BACKGROUND: Intensified examination of the sentinel lymph node (SN) may result in increased detection of tumor-affected lymph nodes. The authors of this report hypothesized that the introduction of the SN procedure has led to stage migration because of the intensified workup of SNs by pathologists. METHODS: After the introduction of the SN procedure, 360 patients with operable breast cancer were included prospectively from 2 large hospitals (Hospital A and Hospital B). The prospectively included patients (the "SN era" group) were compared with 88 historic controls from the year 1994 who were diagnosed with primary breast cancer before introduction of the SN procedure. RESULTS: After correcting for classic clinical and pathologic prognostic factors in a multiple logistic regression analysis, the detection frequency of lymph node involvement was significantly higher in the SN era group compared with historic controls (P = .04). However, when using the 2002 TNM classification, in which isolated tumor cells (

Indeterminate breast fine-needle aspiration: repeat aspiration or core needle biopsy?

Fine-needle aspiration (FNA) of breast lesions provides indeterminate (C1, C3, and C4) diagnoses in a high proportion of cases. The aim of the present study was to retrospectively determine whether repeat FNA or core needle biopsy (CNB) most frequently provides a correct and more conclusive diagnosis. All patients who had an indeterminate primary FNA followed by repeat FNA or CNB within 1 month from 1992 to 2007 were included. FNA was diagnosed as C1-C5; CNB was diagnosed as B1-B5. Improvement in preoperative diagnosis by repeat FNA or CNB was defined as C2/B2 in benign lesions, C3/B3 in premalignant lesions, C4/B4 or C5/B5 in malignant lesions where primary FNA was C1, and C5/B5 in malignant lesions where primary FNA was C3 or C4. Among 255 eligible cases, CNB improved the preoperative diagnosis more often than did repeat FNA (78.0% vs. 54.8%, odds ratio = 2.9, P < .001). When corrected for patient age, appearance on mammogram (mass or not), clinical findings (palpable or not), tumor size, and aspiration mode (freehand vs. image guided), this difference slightly increased (odds ratio = 3.0, P = .001). CNB should be performed after an indeterminate FNA of a breast lesion to obtain a reliable and clear preoperative diagnosis.

Bilateral profound hearing loss due to meningeal carcinomatosis.

Meningeal carcinomatosis (MC) is an uncommon form of metastasis of solid tumors. Hearing loss as the presenting symptom of MC is very uncommon. A patient with an esophageal signet ring cell carcinoma 3 years previously presented with sudden onset of profound hearing loss affecting both ears. He had no evidence of local tumor recurrence. Brain magnetic resonance imaging (MRI) showed swelling and increased signal intensity on T2 weighted images of both acoustic nerves and the right trigeminal nerve. After gadolinium administration, enhancement of both acoustic and trigeminal nerves was seen. He later developed unsteadiness and head-movement-dependent oscillopsia due to vestibular areflexia and diplopia. At that time MRI showed leptomeningeal enhancement. MC was diagnosed, although cerebrospinal fluid cytology could not confirm that diagnosis. The patient died 16 weeks after the onset of deafness. In patients with progressive unilateral and bilateral hearing loss, meningeal carcinomatosis should be considered, especially if there is a history of previous malignancy.

Brain metastasis from prostate small cell carcinoma: not to be neglected.

BACKGROUND: Symptomatic brain metastases from prostatic carcinoma are rare (0.05% to 0.5%). CASE REPORT: A 70-year-old man presented with a homonymous hemianopsia due to brain metastatic prostatic carcinoma shortly before becoming symptomatic of prostatic disease. CT and MRI of the brain showed a tumour deep in the right hemisphere near the thalamus and involving the optic radiation. RESULTS: Routine haematological and biochemical tests were normal. The prostate specific antigen level was low on two separate occasions. The prostatic and brain tumours showed identical appearances, namely of a poorly differentiated adenocarcinoma with neuroendocrine differentiation (small cell carcinoma). CONCLUSION: A literature review suggests that small cell carcinoma of the prostate is more likely to spread to the brain compared to adenocarcinoma and that brain metastases indicate a poor prognosis. The prostate gland should be remembered as a possible cause of brain metastases and that a normal serum prostate specific antigen does not exclude this diagnosis.