The cytologic features of NUT midline carcinoma

BACKGROUND:

Nuclear protein in testis (NUT) midline carcinoma (NMC) represents an aggressive, high‐grade carcinoma typically involving the upper aerodigestive tract or mediastinum. Although the tumor was originally noted in young persons, we have subsequently identified 5 adult cases. To our knowledge, the cytology of NMC has not been systematically described.

METHODS:

We recently published a series of NMCs identified by fluorescent in situ hybridization for characteristic NUT rearrangement. Three of these patients had undergone fine‐needle aspiration. Patient age, sex, primary tumor location, and aspiration site were noted. Cases were assessed for the following: cellularity, architecture, cytoplasm, cell size, nuclear contours, nucleoli, chromatin, anisonucleosis/cytosis, mitotic activity, background, and nuclear crush.

RESULTS:

The 3 cases occurred in 2 women and 1 man, ages 31‐79 years. Primaries involved the sinonasal tract (2) and larynx. Aspirates were of right neck masses (2) and supraclavicular lymph node. Smears were highly cellular and generally noncohesive. Cytoplasm was scant/delicate, although occasional cells with denser cytoplasm were noted in 1 case. Cells were 2‐3 times the diameter of a small lymphocyte with irregular nuclear contours, discrete nucleoli, and fine/granular to vesicular chromatin. Anisonucleosis/cytosis was slight to moderate. Mitotic figures were noted in each case. The background contained naked nuclei and karyorrhectic debris; nuclear crush was noted.

CONCLUSIONS:

NMCs exhibit cytologic features of a poorly differentiated or undifferentiated carcinoma. Although reports mention squamous differentiation as a histologic feature, it is typically focal, and overt squamous differentiation was not identified in our cases. Given morphologic overlap with other high‐grade carcinomas, diagnosis requires a high index of suspicion. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Immunocytochemical characterization of lung tumors in fine-needle aspiration. The use of cytokeratin monoclonal antibodies for the differential diagnosis of squamous cell carcinoma and adenocarcinoma

In the current study, immunocytochemical typing of intermediate filaments was used for a differential diagnosis of human lung tumors from transthoracic fine-needle aspiration biopsies (TFNAB). The authors have compared the cytologic diagnosis of 53 lung cancer cases with the immunofluorescence patterns obtained using a panel of monoclonal antibodies, five of which (KG 8.13, KM 4.62, Ks B.17, KS 8.12, KK 8.60) react with specific cytokeratin polypeptides and one with vimentin (VIM 13.2). Only in six of 23 samples cytologically diagnosed as squamous cell carcinoma did the immunocytochemical typing of cytokeratins (ICTC) confirm the cytologic diagnosis. In seven cases some of the tumor cells stained positively with antibody Ks B.17 specific for simple epithelial keratin (No: 18), suggesting the presence of some cells of glandular origin. In ten additional cases the ICTC was in conflict with the cytologic diagnosis of squamous cell carcinoma (i.e., antibodies Ks 8.12 and KK 8.60 were negative, and antibody Ks B.17, positive) supporting a diagnosis of adenocarcinoma. In 14 of 18 cases cytologically diagnosed as adenocarcinoma, the ICTC confirmed the diagnosis whereas in four cases additional presence of some squamous cells was noticed. The ICTC labeling of cases cytologically diagnosed as undifferentiated and large cell carcinomas was similar to that of the group of adenocarcinomas. Thus, the application of cytokeratin typing for TFNAB samples seems to provide a vital complementation to routine cytologic study, especially for cases cytologically diagnosed as squamous carcinoma.     

Severe cervical glandular cell lesions and severe cervical combined lesions: predictive value of the papanicolaou smear

BACKGROUND: The purpose of the current study was to determine the accuracy of routinely screened cervical smears to predict a glandular cell lesion in histologically confirmed cases of cervical adenocarcinoma in situ (AIS), invasive adenocarcinoma (ADCA), adenosquamous carcinoma (ADSQCA), and severe combined glandular and squamous cell lesions. METHODS: Between 1989-2000, a total of 1,141 women with a histologic diagnosis of cervical AIS, ADCA, ADSQCA, and combined lesions (glandular cell lesion with a coexistent squamous cell lesion) were registered in the Dutch National Pathology Archive (PALGA). In 1054 of these 1,141 histologic cases, an additional conventional Papanicolaou (Pap) smear diagnosis was registered from the same patient. Material was evaluated with regard to the accuracy of cytologic diagnosis, the percentage of combined lesions, the mean age of the patients, and the time interval between AIS and ADCA. RESULTS: Of 1,141 registered histologic cases, 57.5% were registered as having an "intraepithelial" lesion, whereas 42.5% were registered as having an "invasive" process. A combined process was diagnosed in 63.2% of cases. From the same patients, a cytologic diagnosis of a severe cervical epithelial lesion was registered in PALGA for 91.2% (n = 961) of 1054 cases. A cytologic registration of a severe glandular cell lesion (with or without a squamous cell component) was made in 547 cases (51.9%). Prediction of a severe glandular cell lesion on the Pap smear was found to be more accurate in cases of histologically confirmed pure glandular cell abnormalities than in cases with a histologic diagnosis of a combined lesion. The cytologic prediction was found to be correct in 75.2% of cases of pure AIS and 47.3% of cases of AIS with coexistent high-grade squamous intraepithelial lesion (HGSIL) (cervical intraepithelial lesion [CIN] type 2 [CIN 2] or CIN 3). The mean ages of the patients with AIS and AIS + HGSIL were 37.3 years and 34 years, respectively, whereas the mean age of the patients with ADCA and ADCA + HGSIL was 41.9 years and 38.1 years, respectively. The interval between the average ages of patients with AIS and ADCA and those with AIS + HGSIL and ADCA + HGSIL was 4.6 years and 4.1 years, respectively. CONCLUSIONS: On the basis of a data search of the PALGA registry, it can be concluded that in a relatively large number of cases a severe cervical glandular cell lesion was not diagnosed on the Pap smear. Furthermore, data demonstrated that the prediction of a glandular abnormality is less accurate in cases of combined squamoglandular cell lesions than in pure glandular cell lesions.     

Expression of CD44 isoforms in squamous cell carcinoma of the border of the tongue: A correlation with histological grade, pattern of stromal invasion, and cell differentiation

BACKGROUND AND OBJECTIVES: Oral squamous cell carcinoma is a frequent disease with reserved prognosis, where the routinely evaluated morphological features lack a major correlation with prognosis. In order to assess the potential value of the immunoexpression of CD44 isoforms v3, v4-5, and v6, we studied it in a series of 56 consecutive cases of squamous cell carcinomas of the border of the tongue. METHODS: All the histological (World Health Organization grade, Bryne score, degree of keratinization, and pattern of stromal invasion) and immunohistochemistry (using monoclonal antibodies to CD44v) results were exclusively assessed at the deep invasion front of the neoplasms. Downregulation of CD44v was defined by focal or irregular staining of < 10% of the cells at the deep invasive front. RESULTS: There was downregulation of CD44v3 in 37.5% of the cases, CD44v4-5 in 67.9%, and CD44v6 in 33.9%, occurring mostly in cases with low Bryne scores and graded as well-differentiated according to the WHO classification. Downregulation of CD44v was found to correlate with cell differentiation, tumor grade, and the pattern of neoplastic invasion. CONCLUSIONS: Our findings in the present series point to the consideration that CD44v pattern and intensity of immunoexpression in the deep invasive front of squamous cell carcinoma of the tongue are mostly related to tumor grade, the features of stromal invasion, and to the presence of cervical lymph node metastases.     

Severe cervical glandular cell lesions with coexisting squamous cell lesions

BACKGROUND: In the current report, the authors present the results of a reevaluation of cytologic smears and histologic specimens obtained from patients with severe cervical glandular cell lesions (adenocarcinoma in situ [AIS] or adenocarcinoma [ADCA] of the cervix) and coexisting Grade 1, Grade 2, or Grade 3 cervical intraepithelial neoplasia or squamous cell carcinoma. The goal of the current study was to assess whether knowledge of the specific cytologic characteristics of the cervical glandular cell lesions could have made the cytologic diagnosis of these combined neoplasms more accurate. METHODS: Cytologic smears and histologic specimens obtained from 36 patients with combined severe cervical lesions were evaluated for the presence of a range of microscopic cytologic and histologic features that were considered indicative of glandular cell changes. RESULTS: The findings of the current study suggest that the proper identification of characteristic cytomorphologic features of cervical glandular lesions would have resulted in more accurate diagnoses of combined severe cervical lesions. In the set of samples reevaluated by the authors, consideration of these features would have increased the accuracy of cytologic diagnosis from 55.6% to 75.0%. The presence of AIS was predicted in the majority of cytologic specimens, and in most cases, the identity of the predominant subtype of AIS could also be predicted. CONCLUSIONS: The current analysis revealed that consideration of specific cytomorphologic features of glandular lesions of the cervix increased the authors' accuracy in diagnosing combined severe lesions of the cervix. More accurate identification of intraepithelial glandular cell lesions may eventually lead to decreases in cervical adenocarcinoma incidence, just as increases in diagnostic accuracy have led to decreases in the incidence of squamous intraepithelial lesions and invasive squamous carcinoma of the cervix.     

Cytologic diagnosis of rectal melanoma

The cytologic characteristics of malignant melanoma of the rectum are discussed in the paper. The study was based on the data of examination of 13 cases (pigment-free tumor--6 cases). The basic cytologic features of malignant melanoma were diverse cellularity, presence of binuclear cells, and granules or diffuse inclusion of melanin. Three histologic patterns of tumor were identified: epithelioid, spindle-cell and polymorphous cell. Two cases of pigment-free malignant melanoma of the anorectal area were misdiagnosed as squamous cell carcinoma which was due to reactive changes developing in the cells of the stratified squamous epithelium.     

Basaloid squamous cell carcinoma of the sinonasal tract

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a high grade, aggressive variant of squamous cell carcinoma with a predilection for the larynx, hypopharynx, tonsils, and base of the tongue. To the authors' knowledge, BSCC originating in the nasal cavity and paranasal sinuses rarely has been reported. METHODS: Fourteen cases of BSCC involving the nasal cavity and paranasal sinuses were identified in the files of the Otolaryngic-Head and Neck Pathology Tumor Registry of the Armed Forces Institute of Pathology from 1975-1997. Clinical records and follow-up were available in all cases. Paraffin blocks were available for histochemical and immunohistochemical studies in all cases. RESULTS: There were 7 females and 7 males, ages 32-86 years (median, 66.5 years; mean, 62 years). The patients presented primarily with a mass lesion and unilateral nasal obstruction. In nine patients the tumor was confined to the nasal cavity. In three patients the tumor involved the sinuses alone and in two patients the tumor involved the nasal cavity and paranasal sinuses. Histologically, the tumors were widely invasive with a variety of growth patterns, including lobular, solid, trabecular, cribriform, and fascicular. The neoplastic infiltrate included predominantly pleomorphic, basaloid-appearing cells with hyperchromatic nuclei, inconspicuous to prominent nucleoli, and a variable amount of eosinophilic to clear-appearing cytoplasm. Mitotic figures, including atypical forms, were readily apparent as was necrosis (individual cell and comedo-type). Foci of squamous differentiation were limited in extent but were found in all cases and included squamous whorls, individual cell keratinization, and intercellular bridges. Intraepithelial dysplasia, carcinoma in situ, or invasive squamous carcinoma was present in all cases. Other histologic features included intercellular stromal hyalinization and peripheral nuclear palisading. In two cases, neural-type rosettes were found. Immunoreactivity for a variety of epithelial markers including cytokeratin (AE1/AE3/LP34), CAM 5.2, 34betaE12, CK7, and epithelial membrane antigen was present in all cases. Variable reactivity was present with vimentin, actins (smooth muscle and muscle specific), neuron specific enolase, S-100 protein, glial fibrillary acidic protein, CK20, carcinoembryonic antigen, Leu7, and Ewing's marker. Chromogranin, synaptophysin, neurofibrillary protein, leukocyte common antigen, HMB-45, desmin, and Epstein-Barr virus latent membrane protein were absent. Surgical resection was the treatment of choice. Eight patients had recurrent or persistent tumor and metastatic disease occurred in five patients. At last follow-up, 7 patients (50%) had died of disease with a median survival of 12 months from the time of diagnosis and 3 patients were alive with disease over periods ranging from 8 months-5 years. Of the 4 remaining patients, 2 were alive without disease at 1 month and 5 years, respectively, 1 patient was lost to follow-up with no evidence of tumor at 3 years, and 1 patient had died of unrelated causes with no evidence of disease. CONCLUSIONS: Sinonasal BSCC is a histologically distinct variant of squamous cell carcinoma with pathologic features and aggressive biologic behavior similar to BSCC localized to more common mucosal sites of the upper aerodigestive tract.     

Effectiveness of the Thin Prep Imaging System in the detection of adenocarcinoma of the gynecologic system

BACKGROUND: The ThinPrep Imaging System (TIS) has been approved by the U.S. Food and Drug Administration for use to decrease the number of false-negative results in ThinPrep (TP) gynecologic specimens and increase cytotechnology productivity. Although the increased detection of squamous abnormalities using the TIS has been well documented, to the authors' knowledge, data regarding the impact of the TIS in the detection of glandular abnormalities is limited. The goal of the current study was to evaluate the effectiveness of the TIS in detecting glandular abnormalities in cervicovaginal specimens. METHODS: TIS evaluated TP tests with histologic confirmation of adenocarcinoma involving the gynecologic system were included in the current study. Two cytotechnologists independently reviewed the cases for the presence or absence of atypical glandular cells. Review results were correlated with initial cytologic and histologic diagnoses. RESULTS: A total of 124 cases met the criteria for inclusion in the current study. Seventy of these cases (56%) were found to contain atypical glandular cells on the TP slide. TIS was able to identify atypical cells in 97% of these cases (68 of 70 cases). Nine cases initially reported as benign were found to contain atypical glandular cells on secondary review. All but 1 of these cases contained atypical glandular cells detected by the TIS. The majority of these false-negative cases (6 of 9 cases) derived from endometrial adenocarcinoma. No cytologic evidence of a glandular abnormality was found in the 54 remaining cases. CONCLUSIONS: The TIS was found to be effective in identifying atypical glandular cells in specimens containing malignant glandular cells, leading to a full review of the slide.     

胃肠道及胃肠道外间质瘤的临床病理及免疫组化分析

目的:研究胃肠道及胃肠道外间质瘤的临床病理及免疫组化特点。方法:应用光学显微镜观察20例胃肠道及胃肠道外间质瘤的形态特征,用免疫组化SP法检测CD117、CD34、Vimentin、SMA、desmin及S-100等6种抗体的表达情况。结果:20例间质瘤中,女性11例,男性9例,平均年龄59·82岁(27~80岁)。发生部位:胃8例(40%),小肠4例(20%),大肠2例(10%),食管1例(5%),肠系膜4例(20%),大网膜1例(5%)。肿瘤镜下主要由梭形和上皮样细胞组成,有栅栏状、交叉束状、漩涡状及巢状等多种排列。CD117、CD34、Vimentin、SMA、desmin及S-100表达阳性率分别为95%(19/20),75%(15/20),100%(20/20),40%(8/20),5%(1/20)及25%(5/20)。临床症状以腹部包块、腹部不适及消化道出血为主。良性3例(3/20),潜在恶性4例(4/20),恶性13例(13/20)。恶性间质瘤中的核分裂>5/50HPF、肿瘤细胞坏死及细胞密集比良性和低度恶性者常见(P<0·05)。结论:间质瘤多发生于老年人,无性别差异,胃肠道是其好发部位,细胞排列多样,具有多向分化能力,免疫组化证实部分GIST具有不完全的平滑肌、神经单向或双向分化特征。核分裂>5/50HPF、肿瘤细胞坏死及细胞密集是重要的恶性指征。CD117及CD34是其较特异及敏感的抗体,免疫组化在间质瘤的诊断及鉴别诊断中起重要作用。     

Glandular or mucus-secreting components in squamous cell carcinoma of the esophagus

A review of 195 patients with carcinoma of the esophagus disclosed 41 cases (21.0%) with glandular and/or mucus-secreting components, in addition to the ordinary component of squamous cell carcinoma. These tumors could be grouped into three types according to representative histologic features of glandular and mucus-secreting portions: glandular type (23 cases), cribriform type (11 cases), and mucoepidermoid type (7 cases). The histologic features of the three types were reminiscent of those of adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma of salivary glands, respectively. Moreover, areas showing glandular or mucus-secreting differentiation were in greater part located in the submucosa and the lamina propria mucosae, thereby suggesting that such differentiation had arisen in the esophageal glands or their ducts. In all 41 cases, the ordinary element of squamous cell carcinoma, invasive, or noninvasive, was admixed in various proportions with the glandular components, indicating that this type of esophageal tumor had originated not only from the covering squamous epithelium but also from esophageal mucous-gland or ductal epithelium. The findings also support the concept of the field origin of carcinogenesis in esophageal carcinoma.     

Fine-needle aspiration cytology of mucinous tumors of the pancreas

BACKGROUND: Tumors of the pancreas associated with extracellular mucin production include mucin-producing ductal adenocarcinoma, mucinous cystic neoplasm (MCN), and intraductal papillary mucinous tumor (IPMT). Fine-needle aspiration (FNA) is used as an adjunct to radiologic analysis for the preoperative categorization of these tumors. The current study was designed to identify distinctive cytomorphologic features that would be useful for the categorization of mucinous tumors of the pancreas. METHODS: The authors evaluated Papanicolaou smears and Diff-Quik-stained smears of specimens obtained by computed tomography-guided and endoscopic ultrasound-guided FNA of the pancreas in 51 cases of mucinous tumors. In the 19 cases in which the patients underwent surgical excision after FNA, the cytologic features were compared with the histopathologic findings. The remaining cases were categorized as one of the three above-mentioned types of mucinous tumors on the basis of cytomorphologic features identified as indicative of subtype among the cases in which a cytologic-histologic correlation was performed. RESULTS: Among the 19 cases with cytologic-histologic correlation, 2 cases of serous cystadenoma and 2 cases of gastrointestinal duplication cyst were misdiagnosed on cytologic analysis as low-grade MCN. Among the remaining 15 cases, cytologic features by histologic diagnosis were as follows: ductal adenocarcinoma (n = 4): moderate to high cellularity, mild to moderate background mucin, three-dimensional clusters, high nuclear cytoplasmic ratios, and mild to moderate nuclear membrane irregularities; low-grade MCN (n = 5): mild to moderate cellularity, abundant background mucin, small clusters, and flat sheets of relatively bland glandular cells; mucinous cystadenocarcinoma (n = 1): similar to ductal adenocarcinoma but more abundant background mucin; and IPMT (n = 5): moderate to high cellularity, abundant background mucin, and prominent papillary arrangement of tall columnar cells with mild to moderate nuclear atypia. The remaining 32 cases were categorized based on cytology alone as adenocarcinoma with mucin production (n = 24) and low-grade MCN (n = 8). CONCLUSIONS: IPMT and low-grade MCN possess distinctive cytologic features that can be used to diagnose them correctly and distinguish them from one another and from other cystic tumors. Duplication cysts closely mimic low-grade MCN, which can lead to false-positive diagnoses. Because of substantial overlap in cytologic features, mucin-producing ductal adenocarcinoma was unable to be distinguished from mucinous cystadenocarcinoma cytologically.     

A Case of Urinary Bladder Urothelial Carcinoma with Squamous,Glandular, and Plasmacytoid Differentiation

We report an extremely rare case of urothelial carcinoma (UC) of the urinary bladder with diverse histological differentiation into squamous, glandular, and plasmacytoid components. A 65-year-old man presented with gross hematuria. Cystoscopy showed a papillary-growing tumor with a wide-based stalk on the left wall of the urinary bladder. Based on the clinical diagnosis of locally invasive bladder cancer, the patient underwent radical cystectomy. Histological examination of the cystectomy specimen revealed UC with histological differentiation into multiple tumor subtypes. The tumor was composed of squamous cell carcinoma with marked keratinization, adenocarcinoma characterized by tall columnar cells with scattered goblet cells, conventional high-grade invasive UC and UC in situ, and plasmacytoid UC composed of discohesive cancer cells with eccentric nuclei and eosinophilic cytoplasm that diffusely infiltrated the bladder wall through the serosal surface. Immunohistochemically, the loss of membranous E-cadherin expression was noted only in the plasmacytoid UC component. The patient developed local recurrences 2 months postoperatively and died of the disease 6 months postoperatively. It is critical to correctly diagnose the histological variants of UC to predict a patient''s prognosis and to determine the optimal treatment.Key words: Bladder cancer, E-cadherin, Histological variant, Immunohistochemistry, p63, Pathological diagnosis, Prognosis     

Prognostic value of ultrastructural characteristics of dysplastic changes in the esophagus

Dysplasia foci in the esophageal squamous epithelium against the background of various reactions of proliferation were studied by electron microscopy. Slightly altered tissue showed diverse cellularity, with dark cambial elements invariably present. With dysplasia advancing, the cell composition became uniform, with a high nuclear-cytoplasmic index. The dark cell pattern with numerous ribosomes was seen more often than that of keratinized clear cells. Small-cell focal proliferations are highly suggestive of precancer. Electron microscopy may be instrumental in eliciting more information on the risk of esophageal squamous epithelium precancer progressing to cancer since it provides data on cell composition, degree of cell differentiation and polysome formation as well as early signs of keratinization.     

Nucleolar organizer regions in soft tissue sarcomas

Argyrophilic proteins of nucleolar organizer regions (AgNORs) were studied in a series of 65 sarcomas of the soft tissues and 2 cases of fibrohistiocytic tumors of intermediate malignancy. The numbers of AgNORs per nucleus and the size of AgNORs were determined and compared with pathomorphologic parameters such as grading of malignancy, cellularity and tumor diameter. The main finding of this study was that AgNOR counts showed significant differences between low-grade malignant (G 1) and high-grade malignant (G 3) tumors predominantly based on a correlation with the frequency of mitosis. All the other criteria of tumor grading (nuclear pleomorphism, differentiation, amount of necrosis), tumor diameter and cellularity showed no differences with regard to AgNOR counts. Though it was observed that tumor giant cells possessed predominantly coarse granular AgNORs, no correlation was found between AgNOR size and any of the parameters investigated. In spite of a clear statistically significant result gained by an evaluation of all cases, a heterogeneity of AgNORs in relation to mitotic activity within a few histological tumor types could be observed, making it difficult to suggest the determination of AgNORs as a parameter with general validity for all soft tissue sarcomas.     

Effects of pingyangmycin on the growth and differentiation of the transplantable squamous cell carcinoma of forestomach (GS-742) in mice

The effect of pinyangmycin (PYM) on the growth and differentiation of the transplantable squamous cell carcinoma of forestomach (GS-742) in mice was studied by optical and electron microscope. The results showed that PYM had marked growth inhibitory effect on GS-742. Histopathologically, tumor necrosis, fibrosis and infiltration of lymphocytes were obvious in mice treated with PYM. A decrease in mitosis and increase in keratinization were also conspicuous. Ultrastructurally, microvilli on tumor cells were significantly reduced in number with formation of blebs and ruffles; mitochondria were swollen; endoplasmic reticulum was often decreased and dilated; and desmosome and tonofibrils were increased. The results indicate that PYM exerts its growth-inhibitory effect on tumor cells by cell damage, inhibition of mitosis and promotion of differentiation.     

Cytologic scoring of endometrioid adenocarcinoma of the endometrium

BACKGROUND: Endometrial carcinoma is one of the most frequent malignancies in the female genital tract, and its incidence has been increasing in Japan. Histologic grade is an important factor for organizing treatment strategies, including hormone therapy, and for predicting the prognosis of the patient. The objective of this study was to evaluate the applicability and usefulness of cytologic scoring in assessing the morphologic differentiation of endometrioid adenocarcinomas of the endometrium using endometrial smears. METHODS: Sixty-four endometrial cytologic samples of endometrioid adenocarcinomas of the endometrium were used in this study. All patients underwent endometrial cytology before hysterectomy, and the diagnosis was confirmed by histologic examination of the extirpated uterus. Each cytologic specimen was scored according to a scoring system established by the authors. The cytologic grade based on those estimated scores was compared with the histologic grade and clinicopathologic parameters, respectively. RESULTS: The cytologic grade (CG) was correlated positively with the histologic grade. A high cytologic score was correlated with p53 mutation and myometrial invasion and was correlated negatively with estrogen receptor and progesterone receptor status. The concordance rates of cytologic grade with well differentiated (Grade 1), moderately differentiated (Grade 2), and poorly differentiated (Grade 3) histologic grades were 83.3% (35 of 42 tumors), 9.1% (1 of 11 tumors), and 100% (11 of 11 tumors), respectively. The total concordance rate was 73.4% (47 of 64 tumors). The best cut-off value for distinguishing histologic Grade 1 from the others was a cytologic score of 17, representing a sensitivity of 83% and a specificity of 81%. For distinguishing histologic Grade 3 from the others, the best cut-off value was a cytologic score of 20, representing a sensitivity of 100% and a specificity of 83%. CONCLUSIONS: The cytologic scoring system studied for endometrioid adenocarcinoma was useful for predicting histologic grade and tumor malignant potential.     

Adenocarcinoma of the cervix

BACKGROUND: The current study examines 1) the sensitivity of detection of invasive adenocarcinoma of the cervix in a routine cervical screening service, and 2) the frequency in smears of cytologic criteria previously found to be useful in diagnosis. METHODS: Data on women with diagnoses of adenocarcinoma of the cervix accessioned at the Western Australian Cervical Cytology Registry during the period 1993-1998 were examined, where smears had been reported by Western Diagnostic Pathology within three years of the biopsy diagnosis. Smears and biopsy material were reviewed. RESULTS: Thirty-six smears from 24 women were reviewed. Of those, 58.3% had been reported as a possible or definite high grade epithelial abnormality (HGEA). On review it was thought that this could be improved to 77.8%. The screening or diagnostic error was thus 19.4% and the sampling error 22.2%. The likelihood of an individual woman receiving a report of a possible or definite HGEA in the three years before biopsy was 83.3%. In retrospect this could have been improved to 91.7%. Heavy bloodstaining with abundant abnormal glandular epithelium (14 smears) and small three-dimensional or papillary clusters (16 smears) were the most frequent clues to invasion. Tumor necrosis/diathesis was present in eight smears, but easily seen in only four, while marked nuclear pleomorphism and macronucleoli were seen in three and one smears respectively. In cases with a discrepancy between the initial and the review findings, very small amounts of abnormal material (three smears), a resemblance to endometrial cells (one smear), and an unusual appearance of folded monolayered sheets (three smears) contributed to the difficulty of diagnosis. CONCLUSIONS: There were significant sampling and screening/diagnostic errors (22.2% and 19.4%, respectively). Screening and diagnostic errors could perhaps be reduced by a greater awareness of the range of cytologic changes, but these may be subtle. Heavy bloodstaining with abundant abnormal glandular material may be a useful clue to invasive, rather than in situ, adenocarcinoma, even in the absence of tumor diathesis or fully malignant nuclear criteria.     

A review of cytologic findings in neuroendocrine carcinomas including carcinoid tumors with histologic correlation

BACKGROUND: The nosology of neuroendocrine neoplasia has evolved substantially in recent years. The aim of this study was to review the authors' institutional experience and diagnostic accuracy for cytologic specimens of neuroendocrine carcinoma (NEC) and to identify features most suggestive of neuroendocrine differentiation. METHODS: The cytologic and histologic findings of 29 archival NEC in which cytology preceded biopsy or resection were compared. The study was comprised of 6 carcinoid tumors, 3 atypical carcinoid tumors, 17 high grade NEC (5 small cell, 9 large cell, and 3 mixed small/large cell), and 3 combined NEC/nonneuroendocrine carcinomas. Cytologic material was derived from 21 fine-needle aspirates (FNA), 6 bronchial brushing/washings, and 2 gastrointestinal tract brushings. RESULTS: Of the 29 cases, the correct cytologic diagnosis was rendered in 11. Two cases were identified as NEC but were graded incorrectly. The remaining 16 cases were interpreted as nonsmall cell carcinoma (8 cases); diagnostic or suspicious of carcinoma, not otherwise specified (7 cases); and atypical, indeterminate for malignancy (1 case). On review, neuroendocrine features were identified in 14 of the latter 16 cases. CONCLUSIONS: The cytologic diagnosis of NEC, both high and low grade, can be difficult. Because of acinus-like formations and columnar cell shapes, low grade NEC may be mistaken for adenocarcinoma. Small cell carcinomas, especially in bronchial brush and wash preparations, may be difficult to classify beyond malignant. Large cell NEC may be confused with nonneuroendocrine carcinomas because of abundant cytoplasm and nucleoli. Attention to the presence of loose cell aggregates in a background of singly dispersed cells; feathery patterns created by tumor cells clinging to capillaries; rosette formations; delicate, granular cytoplasm; inconspicuous nucleoli; molding in high grade tumors; and, most important, speckled or dusty chromatin patterns are useful in identifying neuroendocrine differentiation in cytologic specimens.     

Cytopathologic grading of hepatocellular carcinoma on fine-needle aspiration

BACKGROUND: Hepatocellular carcinoma (HCC) is routinely graded histopathologically using a modified Edmondson system (ES). The cytologic grading of HCC has been used predominantly as an adjunct in differential diagnoses (i.e., to help distinguish HCC from other tumors as well as nonneoplastic lesions). However, there are unanswered questions regarding the reliability of the cytologic grading of HCC and its correlation with histologic follow-up. METHODS: A total of 106 cases of HCC were identified in the authors' cytopathology files from 1977 to the present. Of these cases, 64 had either a core needle or excisional biopsy sample that was judged to be adequate for histologic grading. From each case smears were graded independently in a blinded fashion by two cytopathologists, and tissue slides were graded by a liver pathologist. The cytopathologists' grading was then adjudicated by considering the histologic diagnosis as the "truth standard". Finally, after the scores were calculated, a statistical analysis was performed to ascertain the accuracy of the cytopathologic grading. RESULTS: The sensitivity for accurate grading was found to be highest for well differentiated (WD) lesions; the specificity was found to be highest for poorly differentiated (PD) HCC for both cytopathologists. Interobserver agreement was highest for WD HCC. WD HCC displayed cohesive fragments, often associated with characteristic vascular/endothelial patterns. In addition, moderately differentiated (MD) HCC demonstrated numerous single cells and atypical naked nuclei, usually with prominent nucleoli. PD HCC displayed loose nests and three-dimensional fragments (often gland-like), pleomorphism, macronucleoli, and focal necrosis. CONCLUSIONS: In the authors' experience, the three-tier cytologic grading of HCC was found to be only moderately accurate. The accuracy of cytologic grading was reported to be high for WD/PD HCC and low for MD HCC. The architectural criteria appear to be more useful for WD HCC, whereas marked cellular pleomorphism is specific for PD HCC. The authors propose that a two-tier grading system may be more useful, given the recent studies of HCC recurrence.