Presence Of Prominent Nucleoli Research Articles

Cytological features of human papillomavirus-infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2.

In reflex cytology, the presence of prominent nucleoli in immature metaplastic squamous cells (IM) may be underdiagnosed due to variations in interpretation. The aim of this study is to identify human papillomaviruses (HPVs) that infect IM clusters in cervical intraepithelial neoplasia 2 (CIN2) on Papanicolaou (Pap) smears to determine the cytological features of lesion-derived cells. Thirty-two patients with a simultaneous diagnosis of CIN2 on biopsy and high-grade squamous intraepithelial lesions (HSIL) on cytology as well as with IM clusters on HSIL smears were included. CIN2 tissues and HSIL and IM clusters on Pap smears were isolated by manual microdissection, and HPV types were identified by PCR-based genotyping. The nuclear area within the IM clusters was also measured. The median nuclear area of HPV-negative IM clusters was 48 μm2 , with a coefficient of variation (CV) of 0.20; those of HPV-positive clusters were 66 μm2 and 0.34, respectively. The cut-off values of the nuclear area and CV for HPV positivity were 62 μm2 and 0.25, respectively. IM clusters composed of cells with a nuclear area of more than twice that of neutrophils or cells with a wide variation in nuclear sizes are likely to be neoplastic cells caused by HPV.

Salivary gland polymorphous adenocarcinoma: Clinicopathological features and gene alterations in 36 Japanese patients.

Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma. We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p= 0.0005), the presence of prominent nucleoli (p= 0.0003), and ARID1A split positivity (p= 0.004) were independent risk factors for disease-free survival. Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.

Correlation of Scanning (SEM) and Transmission Electron Microscopy (TEM) of Human Umbilical Cord derived Mesenchymal Stromal Cells (hUC-MSCs)

Background & Aim Introduction Correlation of surface structures from SEM and ultrastructure from TEM can provide not only valuable information to have a better understanding of functional but also to demonstratethe 3-D aspect of hUC-MSCs. Methods, Results & Conclusion Materials and Methods MSCs isolated from human umbilical cord were seeded and cultured on sterilized cover slides (Day0). For SEM preparation, the cultured cells were fixed on Day4, Day8 and Day12 respectively with glutaraldehyde, dehydrated, critical-point dried, metal sputtering, and observed under the Hitachi S-4800. For TEM preparation, cultured cells were harvested simultaneously, routinely processed and examined under Philips CM100. Results As illustrated in Figure1 Day4 SEM, numerous young MSCs of varying sizes undergoing proliferation were observed on top of the mature MSCs. Note the wide intercellular space but well connected amongst the cultured cells. This correlated well with Day4 TEM (Figure2). Note the wide intercellular spaces in between the cultured MSCs. The cells were characterized with the presence of vacuoles and vesicles of varying sizes and electron-density.Under similar magnification Day8 SEM, surface structures of cultured cells were prominent and well defined; and appeared as one single sheet nicely displayed (Figure3). Similar organization of cultured cells was observed at Day8 TEM. Cultured MSCs were well connected with numerous cytoplasmic processes. Active cellular activity was observed as reflected by the presence of prominent nucleoli and thin rim of chromatin material within the nuclei of some of the cells (Figure4). At Day12 SEM, cultured MSCs were highly congested practically with no intercellular space and tended to form pleated multiple layer. This was confirmed by TEM at Day12. Cells under degeneration were also noted. Conclusion The present study provides information within the context of the 3D ultrastructure of hUC-MSC. Our results showed that hUC-MSC cultured at Day8 (P0) is desirable for further expansion for research purpose or clinical applications.

Histopathological Changes in Breast Cancers Following Neoadjuvant Chemotherapy: Implications for Assessment of Therapy-Induced Cytological and Stromal Changes for Better Clinical Outcome and Effective Patient care

AbstractThe histopathological interpretation of a tumor still remains the gold standard for diagnosis and deciding the type of therapy. Furthermore, in the context of chemo-radio-therapies often leading to prominent cytological and stromal changes in the tumor, histopathological interpretation during treatment, thus, becomes all the more important in correctly diagnosing and grading the tumor for an effective and planned regimen of the therapy increasing prognosis and chances of survival of the affected patients. The aim of the present study was to evaluate such cytological and stromal changes rendered by the therapy during treatment in breast cancer cases. The present study was conducted over a period of 4 years from January 2014 to June 2017 at Kasturba Medical College, Mangalore, Karnataka, India wherein the clinical and histopathological details were collected for a total of 39 breast carcinoma cases during and post-therapy. Statistical analysis was done using IBM SPSS statistics 17 (Chicago, USA). Various morphological features were analyzed for their frequency and were compared with the final diagnosis using Chi-square value (χ2), paired t-test and Fischer's test. p-value < 0.05 was considered to be statistically significant. The results of the present study revealed that 32 of the 39 breast carcinoma cases changed their grades during the course of therapy (p-value < 0.05). The fundamental manifestation of the effect of therapy was an obvious decrease in tumor cellularity. Intracellular changes commonly noted after chemotherapy included nuclear enlargement, hyperchromasia and an increased N:C ratio which were found in upto 85% of the cases followed by presence of prominent nucleoli and karyorrhexis/karyolysis. The predominant stromal changes seen post-therapy included necrosis (74.4%), fibrosis (64.1%), desmoplasia (59%) and degenerative changes (33.3%). Breast cancer therapy causes morphological alterations in the cancerous as well as the surrounding healthy tissue. The histopathological interpretation in such cases, thus, requires a thorough knowledge of the cytological and stromal changes rendered by the therapy.

Acteoside-mediates chemoprevention of experimental liver carcinogenesis through STAT-3 regulated oxidative stress and apoptosis.

In the absence of an effective therapy against Hepatocellular Carcinoma (HCC), chemoprevention remains an important strategy to circumvent morbidity and mortality. Here, we examined chemopreventive potential of Acteoside (ACT), a plant derived phenylethanoid glycoside against an environmental and dietary carcinogen, diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. ACT treatment (0.1 and 0.3% supplemented with diet) started 2 weeks before DEN challenge and continued for 18 weeks thereafter, showed a remarkable chemopreventive activity. ACT treatment resulted in reduced HCC nodules. Histopathology showed progressive tissue damage, necrosis (5 weeks), hepatocytic injury (10 weeks), anisonucleosis with presence of prominent nucleoli, sinusidal dilations, and lymphomono nuclear inflammation (18 weeks). Biochemical analysis showed hepatocytic injury (raised ALT, p < 0.001), inflammation [IL-6, IFN-γ (p < 0.05), and TNF-α (p < 0.001)], apoptosis [elevated Caspase-3 (p < 0.001)]. ACT at 0.1 and 0.3% ameliorated DEN-induced pre-hepatocarcinogenic manifestations. Mechanistic studies of ACT chemoprevention was elucidated using Hep3B cells with an aim to develop an in vitro DEN-induced toxicity model. Hep3B was found to be a reliable and more sensitive towards DEN toxicity compared to HepG2 and HuH7 cells. ACT prevented DEN-induced cytotoxicity (p < 0.001), DNA damage, and genotoxicity (micronuclei test, DNA ladder test, Hoechst staining, cell cycle analysis). ACT significantly (p < 0.001) scavenged DEN-induced reactive oxygen species (ROS) levels and prevented mitochondrial membrane potential (MMP) loss. Immunoblotting showed ACT treatment reversed DEN-induced NF-κB, Bax, Cytochrome C, Bcl-2, and Stat-3 levels. We conclude that chemoprotective effect of ACT is mediated by STAT-3 dependent regulation of oxidative stress and apoptosis and ACT has potential to be developed as a chemopreventive agent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 782-798, 2016.

Frequency of the morphological criteria of prostate adenocarcinoma in 387 consecutive prostate needle biopsies: emphasis on the location and number of nucleoli

Introduction and objectives: We evaluated the sensitivity and specificity of morphological criteria for the diagnosis of prostate adenocarcinoma in consecutive, prostate needle biopsies specimens with emphasis on the location and number of nucleoli. Methods: The morphological features of 387 consecutive prostate needle biopsies specimens, in 2013, were systematically examined and stratified according to the final diagnosis of benign, suspicious and malignant lesions. We also tested how well each criterion predicted the final diagnosis after the immunohistochemical evaluation for expression of the basal cell markers (p63 and high molecular weight cytokeratin) and racemase. Results: A prominent nucleoli is the most common feature of carcinoma; however it is also relatively common in benign cases. The frequencies of prominent central nucleoli in malignant, suspicious and benign cases were 99%, 89% and 27%, respectively. Marginated nucleoli (85%, 60% and 7%), double nucleoli (86%, 53% and 10%), and multiple nucleoli (47%, 14% and 2%) were less common in benign cases, with significant difference among the groups. From the 36 cases initially diagnosed as suspicious, the presence of marginated nucleoli and mitoses were associated with the final diagnosis of malignancy. Prominent central nucleoli were more associated with cases which the final diagnosis after immunohistochemistry was benign. Conclusion: The location and number of nucleoli may be valuable morphological markers to identify suspicious lesions, since these features are more specific for malignancy than nucleolar prominence. The presence of prominent nucleoli commonly leads to the initial diagnosis of suspicious lesion that, subsequently, will be resulted in benignity confirmed by immunohistochemistry.

Intestinal metaplasia of the sinonasal mucosa adjacent to intestinal-type adenocarcinoma. A morphologic, immunohistochemical, and molecular study.

It has been hypothesized that the development of sinonasal intestinal-type adenocarcinoma (ITAC) occurs through intestinal metaplasia (IM) of the respiratory and/or glandular epithelium. The aim of this study was to characterize the histological, immunohistochemical, and molecular features of sinonasal IM. Histologic slides from 29 consecutive surgical specimens of ITAC were retrieved. Sections were stained for CDX2, cytokeratin 20 (CK20), MUC2, and p53. The status of TP53 gene exons 4-9 was assessed separately in areas of IM and in ITAC. Foci of IM were detected in eight cases (27.5%). They were all positive for CK20 and CDX2, while MUC2 was detected in six cases (75%). In six cases (75%), the metaplastic foci showed signs of dysplasia, including nuclear enlargement with increased nucleus to cytoplasm ratio, nuclear hyperchromasia, loss of nuclear polarity, and presence of prominent nucleoli. P53 nuclear immunoreactivity was observed in four cases. TP53 gene sequencing was successfully performed in six cases and revealed the same mutation in both IM and ITAC in two cases (c.832C > T and c.215G > C), while another ITAC showed a mutation that was not present in the adjacent IM (c.536A > G). In conclusion, our study suggests a possible clonal relationship between areas of sinonasal IM and ITAC, indicating that IM may represent a precursor lesion of ITAC. Improving the knowledge on the morphological and molecular features of IM is a key step to identify reliable biomarkers to determine the risk of sinonasal ITAC development.

A comprehensive morphological study for basal-like breast carcinomas with comparison to nonbasal-like carcinomas

BackgroundBreast carcinomas can be classified into five subtypes based on gene expression profiling or immunohistochemical characteristics. Among these subtypes, basal-like breast carcinomas (BLBCs) are one of the most studied group, due to their poor prognosis. The aim of this study was to investigate the prevalance, morphological and immunohistochemical features of BLBCs, in Turkish population.MethodsFive hundred invasive breast carcinomas were reviewed for several morphological features and immunostained for oestrogen and progesterone receptors, c-ERB-B2, cytokeratin5/6, cytokeratin14, vimentin and epidermal growth factor receptor (EGFR). Basal-like breast carcinoma was defined as a triple negative tumor with cytokeratin5/6 and/or EGFR positive.ResultsThe prevalance of BLBC was 9.6%. All medullary carcinomas and 55.6% of metaplastic carcinomas showed basal-like immunophenotype. Patients with BLBC were younger (p=0.04) and had higher-grade tumors (p<0.0001). Morphologic features associated with BLBC included increased mitosis, nuclear pleomorphism, presence of geographic and/or central necrosis, pushing margin of invasion and stromal lymphocytic response (p<0.0001). Presence of prominent nucleoli and vesicular nuclear chromatin were the cytological features correlated with basal-like phenotype (p<0.0001). On multivariate analyses, BLBCs were associated with high mitotic number (p<0.0001), the presence of vesicular chromatin (p=0.004), high tubular grade (p=0.011), lymphocytic response (p=0.031) and the absence of carcinoma insitu (p=0.039). Vimentin was positive in 53.2% of BLBCs, while cytokeratin14 was less frequently expressed (27.7%).ConclusionsBLBCs have some distinctive, but not pathognomonical, morphological features. Paying attention to these features and adding cytokeratin14 and vimentin to the immunohistochemical panel can help the definitive diagnosis of BLBCs.Virtual slideHttp://www.diagnosticpathology.diagnomx.eu/vs/5962175467857400

Luteinized Adult Granulosa Cell Tumor—A Series of 9 Cases

Most adult granulosa cell tumors (AGCTs) consist of small-to-medium cells with scanty cytoplasm imparting a "small blue cell" appearance. We report 9 cases of luteinized AGCT, whose appearance differs from typical AGCT by the presence of abundant eosinophilic cytoplasm in at least 50% of tumor cells. These tumors were identified in patients aged between 37 and 80 years, all but 1 of whom were postmenopausal. The tumors ranged in size from 4.4 to 14 cm, usually had a yellow cut surface, were unilateral in 7 cases, bilateral in 1 case, and presented as a pelvic mass posthysterectomy in 1 case. Endometrial proliferative changes were present in 7 of 7 (100%) of the postmenopausal patients, a higher percentage than that reported in typical AGCT. The luteinized component occupied 50% to 90% of the tumors that were examined. Morphologic differences from typical AGCT were the luteinization of cytoplasm, relative lack of nuclear grooves, the presence of prominent nucleoli, and a myxoid stroma. The luteinized areas, especially when widespread, resulted in consideration of a wide range of other primary and metastatic ovarian neoplasms containing oxyphilic cells. Immunohistochemistry was useful in confirming a sex cord-stromal tumor, but of no value in the distinction from other neoplasms in the same category. Pathologists should be aware of the existence of luteinized AGCT, an uncommon variant of AGCT, to avoid an erroneous diagnosis.

Neuroblastomas with Discordant Genotype-Phenotype Relationships: Report of Four Cases with MYCN Amplification and Favorable Histology

MYCN amplification prevents cellular differentiation and promotes mitotic and karyorrhectic activities in neuroblastomas. Hence, MYCN-amplified tumors typically show an appearance of neuroblastoma of either an undifferentiated or a poorly differentiated subtype with a high mitosis-karyorrhexis index. In addition, they are classified as part of the unfavorable histology group, according to the International Neuroblastoma Pathology Classification. Large cell type and/or presence of prominent nucleoli is also reported to be an additional hallmark of MYCN amplification. However, there are few neuroblastomas having MYCN amplification and favorable histology. Four cases of MYCN amplification and favorable histology were identified in our file of 63 cases of neuroblastoma. The patients (M∶F  =  3∶1) were diagnosed between 6 and 13 months of age, and all had adrenal primary tumors and were treated with high-dose therapy and autologous stem cell rescue. Three patients (stages 1, 3, and 4) are alive and well 7 years, 26 months, and 19 months after diagnosis, respectively. One patient with stage 4 disease died 8 months after diagnosis. Their tumors showed the same histologic feature of neuroblastoma: poorly differentiated subtype with a low mitosis-karyorrhexis index; they were not qualified as large cell type and had no prominent nucleoli. MYCN amplification of those tumors was confirmed by fluorescence in situ hybridization in all 4 cases, but MYCN protein expression was not demonstrated by immunohistochemistry (4 cases) and MYCN mRNA was not detected by reverse transcriptase polymerase chain reaction (1 case). Those cases showed a discrepant genotype-phenotype that was not simply a laboratory observation but could indicate the concept that that MYCN amplification did not automatically equate to a poor prognosis in this group of patients.

Basal Cell Hyperplasia in the Peripheral Zone of the Prostate

Basal cell hyperplasia in the prostate is often viewed as a transition zone proliferation, related to usual, nodular glandular, and stromal hyperplasia. Basal cell hyperplasia in the prostatic peripheral zone, the most common site for development of prostatic intraepithelial neoplasia and carcinoma, has not been previously characterized. We characterized the incidence and histomorphological attributes of basal cell hyperplasia in a series of 500 consecutive sextant needle core biopsy samples and in 26 completely embedded prostate glands from radical prostatectomy specimens. Comparative proliferation indices (by MIB-1 staining) and apoptotic indices (by TUNEL labeling) were quantitated for peripheral zone versus transition zone basal cell hyperplasia versus normal basal cells. The incidence of basal cell hyperplasia in prostate needle biopsy tissue was 10.2% (51 of 500 cases). Usual basal cell hyperplasia was detected in 8.2% of the 500 cases, and basal cell hyperplasia with prominent nucleoli, in 2.0% of cases. Basal cell hyperplasia in needle biopsy tissue was typically focal and associated with inflammation, which was usually lymphocytic, in 84% of cases. Peripheral zone basal cell hyperplasia was found in 23% of whole prostate glands. Peripheral zone basal cell hyperplasia was not observed to be in direct physical continuity with intraepithelial or invasive neoplasia. Peripheral zone and transition zone basal cell hyperplasia exhibited similar mean proliferation and apoptotic indices, at 1% and 0.07%, respectively. This proliferation index was elevated, and apoptotic index was decreased, relative to normal basal cells (P = 1 × 10−7). Basal cell hyperplasia in the peripheral zone is present in a significant minority of prostate needle biopsy samples and whole prostate glands. The presence of prominent nucleoli in basal cell hyperplasia may cause diagnostic concern for a neoplastic proliferation. The increase in cell number in basal cell hyperplasia appears to be due to a coordinate increase in proliferation index coupled with a diminished apoptotic index. The presence of inflammation in the majority of basal cell hyperplasia foci suggests that peripheral zone basal cell hyperplasia in untreated patients may represent a stereotyped response to injury such as that sustained because of inflammation.

Endoscopic ultrasound guided fine-needle aspiration cytology of pancreatic carcinoma: a 3-year experience and review of the literature.

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) of small pancreatic lesions that are undetectable by computed tomography has gained wide acceptance for the procurement of cells for diagnostic purposes. However, this technique is not without difficulty. The authors examined the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of this technique in the evaluation of patients with pancreatic biliary duct strictures/masses. The authors were interested in reviewing their cases of pancreatic adenocarcinoma of ductal type and finding the sources of their false-negative cases. A computer search was performed between January 1998 and July 2001. For the last 3 years, a total of 80 cases of suspected ductal adenocarcinoma of the pancreas was identified. Thirty-four patients (42%) underwent a subsequent Whipple procedure or biopsy. Cytologic and histologic correlation was performed in these cases. The rest of the 23 patients (29%) considered to be positive and the 23 patients (29%) considered to be negative underwent no subsequent biopsy and were followed clinically. Cases termed "suspicious" on cytology were considered positive and those termed "atypical cytology" were considered negative in the authors' final calculation. The causes of the false-negative diagnoses were evaluated carefully. Of the 34 cases followed with subsequent tissue biopsy or surgery; 12 were confirmed to be positive, 12 were confirmed to be negative, and 10 were considered to be false-negative. Previously identified cytomorphologic features of malignancy were used to review all cases. These features were: loss of the honeycomb pattern (100%), anisonucleosis (100%), nuclear contour irregularity (100%), a high nuclear/cytoplasmic ratio (100%), paranuclear chromatin clearing (77%), and the presence of prominent nucleoli in the absence of inflammatory cells (77%). The causes of the 10 false-negative cases were technical difficulty of procuring material in 6 cases, the nature of the lesion in 2 cases, and the scarcity of lesional tissue in 2 cases. Using strict cytoarchitectural and cytomorphologic criteria of malignancy for ductal pancreatic lesions previously described in the literature, the sensitivity of this technique at the study institution was 78% with a specificity of 100%. The PPV and NPV of this technique were 100% and 78%, respectively. The most common causes of the false-negative results in descending order were the technical aspect of the procedure, the size and nature of the lesion, and the scarcity of lesional tissue.

Diagnostische Kriterien des Prostatakarzinoms

The histological diagnosis of prostate cancer relies on a combination of structural and cytological findings. Structural features are assessed at low power magnification. Malignant glands are recognised by their abnormal size, shape and location in relation to the surrounding benign glandular structures. The presence of pathological intraluminal secretions (pink amorphous secretions, crystalloids, blue-tinged mucinous secretions) is always suspicious, but not diagnostic for prostate cancer. Cytological criteria including nuclear and nucleolar enlargement, hyperchromasia and cytoplasmic changes have to be evaluated in comparison with the cytological features of surrounding benign glands. The presence of prominent nucleoli is neither diagnostic for malignancy nor represents an absolute requirement for the diagnosis of prostate cancer. The basal cell layer is absent in invasive adenocarcinoma, an important feature that has to be evaluated with care since benign glands may also lack detectable basal cells. The immunohistochemical demonstration of basal cells with high molecular weight cytokeratins excludes invasive cancer. This article reviews the histological criteria for the diagnosis of prostate cancer, including variants of common adenocarcinoma and therapy-induced changes.

Interaction between melatonin and estradiol on morphological and morphometric features of MCF-7 human breast cancer cells.

Melatonin has been shown to have a direct inhibitory effect on the proliferation of estrogen-responsive MCF-7 human breast cancer cells, involving an interaction with estradiol. The anti-proliferative effect of melatonin is reversed by the addition of estradiol to the culture. In the present study, we examined whether inhibition by melatonin and subsequent estrogen rescue of MCF-7 cells are correlated with morphological and morphometric changes in these cells. After 4 days of exposure to melatonin, MCF-7 cells showed significantly smaller cell and nuclear sizes than other groups. These morphometric results were closely related to the ultrastructural features observed in these cells. While control and estradiol-treated cells showed increased tumor characteristics, melatonin-treated cells presented greater differentiation, in keeping with their epithelial origin (presence of cytokeratin filament bundles, conspicuous rough endoplasmic reticulum, and Golgi cisternae together with the presence of prominent nucleoli at the nuclear level). Additionally, some melatonin-treated cells displayed degenerative features (mitochondrial swelling with disruption of cristae, cytoplasmic vacuolation, nuclear chromatin disgregation and cell lysis). The addition of estradiol to cells previously incubated with melatonin reversed the changes induced by the latter and these cells showed the same ultrastructural features as the control cells. Our results support the notion that melatonin exerts its antitumor effect through a cell-cycle-specific mechanism by delaying the entry of MCF-7 cells into mitosis. This allows the tumor cells to achieve greater differentiation. The fact that the morphometric and morphological effects induced by melatonin are counteracted by estrogens suggests a cell-cycle acceleration induced by estradiol.

Solitary plasmacytomas of bone and extramedullary plasmacytomas. A clinicopathologic and immunohistochemical study.

Twenty-two patients with solitary plasmacytoma of bone (SPB) and 13 with extramedullary plasmacytomas (EMP) were studied. The average follow-up period for SPB was 90 months and 86 months for EMP. Thirty-six percent of patients with SPB developed multiple myeloma (MM) in an average of 39 months, and 23% of patients with EMP developed MM in an average of 23 months. No significant differences in survival, incidence of MM, or interval to the development of MM were found between the two groups. The 11 cases of EMP with evaluable tissue for immunohistochemical study were either monotypic kappa or lambda, as were 9 of 10 SPB. Presence of monoclonality did not predict the development of MM. The histologic parameters of nuclear immaturity and presence of prominent nucleoli seem to be the best indicators of which patients will develop MM. Solitary plasmacytoma of bone and EMP appear to be more closely related than has been previously recognized.

Sputum Cytology of Hepatocellular Carcinoma Metastasizing to the Lung: A Case Report

A 54 year old male was admitted to Hamanomachi Hospital complaining of discomfort in the right upper quadrant of the abdomen in Aug., 1978. A diagnosis of hepatic tumor was made by scintigram and angiography. Chest X-ray taken in September revealed an ill-defined mass density in the left hilar region. His general conditions became steadily worse and he expired on October 25, 1978. Autopsy confirmed hepatocellular carcinoma and its metastasis to the left lung. Tumor cells were present in the bronchial lumen microscopically. The sputum was collected for cytology three weeks prior to his death.The characteristics of these tumor cells in sputum were presented, i. e. considerable variation in size and shape, a fairely large N/C ratio, trend of multinucleation, etc.Cytology of hepatocellular carcinoma has been reported regarding ascitic fluid and aspiration smears of the liver. They unanimously pointed out the presence of prominent nucleoli, whereas in our case, nucleoli were not clearly seen.