Infiltrative Glands Research Articles

Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice

Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.

Extremely well-differentiated adenocarcinoma of the stomach: diagnostic pitfalls in endoscopic biopsy.

BackgroundExtremely well-differentiated adenocarcinoma (EWDA) is a deceptively bland-looking adenocarcinoma of the stomach. It often causes diagnostic problems, especially in endoscopic biopsy samples. To better recognize this deceptively bland lesion, we carefully reviewed a series of EWDAs treated at our institution.MethodsA total of 55 specimens from 19 patients were obtained. Endoscopic, gross and microscopic features defining EWDA were described and documented. For comparison, hyperplastic polyp specimens were randomly selected and analyzed.ResultsMost cases (18 of 19, 94.7%) were advanced gastric cancer (AGC) and primarily located in the body of the stomach (15 of 19, 79.0%). The majority of AGCs were non-ulcerated (11 of 18, 61.1%) with an undermining growth pattern and a relatively small mucosal involvement. Specific histologic features included an irregular glandular shape, an undulating apical cytoplasmic border, disproportionately large glands, a variably distended mucinous cytoplasm. Classical features, such as small infiltrating glands or desmoplastic reactions, were barely observed. Identification of irregularly spaced nuclei and disruption of the foveolar epithelial structure, along with atypical features described above were helpful in making a diagnosis especially in gastric forceps biopsies.ConclusionsAwareness of the histomorphologic characteristics described in this report would lead to timely diagnosis and prevent repeated endoscopic procedures.

Risk of recurrence in patients with MELF (microcystic, elongated and fragmented) pattern of invasion based on lymph node evaluation status

Objectives: Background. Myometrial invasion with an infiltrative gland pattern has been recently associated with higher stage, lymphovascular invasion, and recurrence. Additionally, a readily recognizable pattern of myometrial invasion characterized by microcystic elongated and fragmented (MELF) glands surrounded by myxoid and inflamed stroma has been associated with lymphovascular invasion (LVSI) and lymph node metastases. Although it is known that MELF increases the risk of a patient having lymph node metastases as well as MELF being associated with LVSI, we sought to understand whether MELF without lymph node metastases or lymphadenctomy portends a worse oncologic prognosis. Methods: We retrospectively reviewed all patients with endometrial cancer who underwent hysterectomy at a single institution between Jan 1, 2010 to Aug 1, 2020 with MELF pattern of invasion identified. Pathology was reviewed by a single reviewer (RM) with subspecialty training in gynecologic pathology. The electronic medical record was utilized to obtain preoperative, perioperative, and follow-up data. These patients were divided based on if they had not had a lymph node evaluation (Group A) or by the performance of lymph node evaluation (Group B). Results: Forty-one patients were identified as having MELF on their hysterectomy specimen. All patients had well-differentiated to moderately differentiated tumors. There was a similar proportion of patients how had LVSI in either group (Group A 80% vs Group B 92.3%). In this cohort, 63.4% underwent an evaluation of the retro-peritoneal lymph nodes, with 92.3% having a complete lymphadenectomy [Table 1]. As compared to Group B where only 7.7% had no adjuvant treatment, 53.3% in Group A were observed. No patients recurred in Group B, while 20% recurred in those without any lymph node evaluation. Looking specifically at the patients who had MELF without lymphadenectomy and recurred, all 3 patients had LVSI and were early stage, thus were at high risk for lymph node involvement. Download : Download high-res image (332KB) Download : Download full-size image Conclusions: In our study, patients with MELF pattern of invasion without lymph node evaluation at the time of hysterectomy were more likely to have no adjuvant therapy and recur than those who underwent lymphadenectomy. Additional multi-institution study should be done to further elucidate the nuances associated with MELF with and without LVSI in patients with early stage endometrial cancer who have undergone lymphadenectomy as this uterine characteristic is not factored in to any of our phase III randomized data.

Reproducibility of AJCC Criteria for Classifying Deeply Invasive Colon Cancers Is Suboptimal for Consistent Cancer Staging.

The eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual attempts to address ambiguity in the pT category assignment for colon cancer from prior editions. Despite modifications, the distinction between the pT3 and pT4a categories continues to be a source of diagnostic confusion. In this study, we assessed interobserver agreement among pathologists from different institutions in the application of AJCC eighth edition criteria for categorizing deeply invasive colonic adenocarcinomas. We identified morphologic patterns that produce diagnostic confusion. We assessed 47 colon cancers that closely approached the serosal surface. Six pathologists with interest in gastrointestinal pathology and 4 focused in other subspecialties classified each case as pT3 or pT4a, based on examination of low-magnification and high-magnification images of the most deeply invasive area. Interobserver agreement was assessed using Fleiss' κ. Cases displayed 3 morphologic patterns at the advancing tumor edge, namely, (1) continuous invasion through an inflammatory focus, (2) pushing border, and (3) infiltrative glands and cell clusters with serosal reaction. Gastrointestinal pathologists achieved slight (κ=0.21) or moderate (κ=0.46) and (κ=0.51) agreement in each category, whereas agreement among nongastrointestinal pathologist was fair (0.31) and (0.39), or moderate (0.57) for each category, respectively. In 10 (21%) cases, the distinction between pT3 and pT4a would have changed the overall clinical stage. We conclude that histologic criteria for serosal penetration is a persistent source of diagnostic ambiguity for gastrointestinal and general pathologists in the pT categorization of colon cancers. Clarification of these criteria will help ensure uniform reporting of pathologic and clinical stage.

Myoinvasive Pattern as a Prognostic Marker in Low-Grade, Early-Stage Endometrioid Endometrial Carcinoma.

Low-grade and early Federation for Gynecology and Obstetrics (FIGO) stage endometrioid endometrial carcinomas (EEC) have an excellent prognosis. However, approximately 10% of patients develop recurrence, which cannot be correctly predicted at diagnosis. We evaluated myoinvasive patterns as a prognostic factor of relapse in low-grade, early-stage EEC. Two-hundred and fifty-eight cases were selected according to the following inclusion criteria: (i) endometrioid endometrial carcinomas, (ii) grade 1 or 2 with (iii) FIGO stage I or II, and (iv) clinical follow-up. Slides were reviewed to annotate the myoinvasive pattern present in each case (infiltrative glands, microcystic, elongated and fragmented –MELF-, broad front, adenomyosis-like and adenoma malignum). Microsatellite instability was studied by immunoexpression of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6). There were 29 recurrences (11.2%) among the 258 cases analysed. A predominant broad front myoinvasive pattern was significantly associated with tumour relapse (p = 0.003). The presence of a pattern of infiltrative glands (p = 0.001) and microsatellite instability (p = 0.004) were associated with lower disease-free survival, without having an impact on overall survival. Our observations suggest the potential value of the pattern of myoinvasion as a prognostic factor in low-grade, early-stage endometrioid endometrial carcinoma.

New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome

We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphovascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.8months. Seventy-three patients (21%) had pattern A tumors; all were stage I and there were no LN metastases or recurrences. Pattern B was seen in 90 tumors (26%); all were stage I and LVI was seen in 24 cases (26.6%). Nodal disease was found in only 4 (4.4%) pattern B tumors (one IA2, two IB1, one IB not further specified (NOS)), each of which showed LVI. Pattern C was found in 189 cases (54%), 117 had LVI (61.9%) and 17% were stage II or greater. Forty-five (23.8%) patients showed LN metastases (one IA1, 14 IB1, 5 IB2, 5 IB NOS, 11 II, 5 III and 4 IV) and recurrences were recorded in 41 (21.7%) patients. This new risk stratification system identifies a subset of stage I patients with essentially no risk of nodal disease, suggesting that patients with pattern A tumors can be spared lymphadenectomy. Patients with pattern B tumors rarely present with LN metastases, and sentinel LN examination could potentially identify these patients. Surgical treatment with nodal resection is justified in patients with pattern C tumors.

Invasive endocervical adenocarcinoma: a new pattern-based classification system with important clinical significance.

A new 3-tier pattern-based system to classify endocervical adenocarcinoma was recently presented. In short, pattern A tumors were characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture. Pattern B tumors demonstrated localized destructive invasion defined as desmoplastic stroma surrounding glands with irregular and/or ill-defined borders or incomplete glands and associated tumor cells (individual or small clusters) within the stroma. Tumors with pattern C showed diffusely infiltrative glands with associated extensive desmoplastic response. In total, 352 cases (all FIGO stages) from 12 institutions were identified. Mean patient age was 45 years (range, 20 to 83 y). Forty-nine (13.9%) cases demonstrated lymph nodes (LNs) with metastatic endocervical carcinoma. Using this new system, 73 patients (20.7%) were identified with pattern A tumors (all stage I); none had LN metastases and/or recurrences. Ninety patients (25.6%) were identified with pattern B tumors (all stage I); only 4 (4.4%) had LN metastases; 1 had vaginal recurrence. The 189 (53.7%) remaining patients had pattern C tumors; 45 (23.8%) of them had LN metastases. This new classification system demonstrated 20.7% of patients (pattern A) with negative LNs, and patients with pattern A tumors can be spared of lymphadenectomy. Patients with pattern B tumors rarely presented with metastatic LNs, and sentinel LN examination could potentially identify these patients. Aggressive treatment is justified in patients with pattern C tumors.

MP53-01 PERFORMANCE OF MULTI-PARAMETRIC MRI FOR HIGH GRADE PROSTATE CANCER: CORRELATION WITH WHOLE-MOUNT PATHOLOGY

INTRODUCTION AND OBJECTIVES: Higher Gleason score (GS) is associated with increased level of suspicion on multi-parametric magnetic resonance imaging (mp-MRI) of the prostate, but some tumors still evade detection by MRI. The objective of this study was to characterize the performance of mp-MRI for detection of high GS tumors and identify risk factors for missed tumor detection. METHODS: A retrospective study was performed of 122 consecutive men who underwent mp-MRI prior to radical prostatectomy from 10/2010-2/2013. Clinical, MRI, and pathologic features were obtained. A genitourinary radiologist and pathologist collectively reviewed each case and matched the MRI to whole-mount pathology lesions. Index tumor was defined as the highest GS tumor; in cases of multifocal tumors of identical GS, the largest tumor was considered the index. Chi-square or Fisher’s exact analysis was performed for categorical and t-test for continuous variables. RESULTS: 180 regions of interest were identified by mp-MRI and 283 tumors were histologically confirmed among 122 men. Among the 57 tumors determined to be GS 4+3, 15/57 tumors (26%) were missed by mp-MRI in 11/50 men (22%), corresponding to a sensitivity of 74%. Index tumor status, tumor size, number of whole mount levels involved, and presence of extra-capsular extension were all associated with tumor detection (p<0.05) (table). 37/44 (84%) of index tumors were correctly identified by mp-MRI. Missed tumors were: less likely to be index tumors (47% vs 88% of MRI-pathology concordant tumors); likely to be smaller (1.24 cm 0.78 cm SD vs 2.41 2.06 SD), involving fewer whole-mount levels; and less likely to have extra-capsular extension (13% vs 55%). Of missed non-index tumors, 4/8 (50%) of the corresponding index tumors were detected by mp-MRI. Of the missed index tumors, no corresponding non-index tumors were detected; review of these slides demonstrated tumor infiltrating benign glands (3/7), small volume tumor within large overall prostate volume (3/7), or abundant foamy gland variant pathology (2/7) as possible reasons for missed tumor detection. CONCLUSIONS: High Gleason score tumors evaded mp-MRI detection in 26% of cases. Smaller, non-index, organ-confined tumors were more likely to be missed; there may be a histologic basis for nonvisualization of tumors by mp-MRI. Table Characteristics of tumors missed versus detected by mp-MRI.

MP53-02 IMPACT OF MULTIFOCALITY ON PROSTATE CANCER DETECTION BY MULTI-PARAMETRIC MRI

INTRODUCTION AND OBJECTIVES: Higher Gleason score (GS) is associated with increased level of suspicion on multi-parametric magnetic resonance imaging (mp-MRI) of the prostate, but some tumors still evade detection by MRI. The objective of this study was to characterize the performance of mp-MRI for detection of high GS tumors and identify risk factors for missed tumor detection. METHODS: A retrospective study was performed of 122 consecutive men who underwent mp-MRI prior to radical prostatectomy from 10/2010-2/2013. Clinical, MRI, and pathologic features were obtained. A genitourinary radiologist and pathologist collectively reviewed each case and matched the MRI to whole-mount pathology lesions. Index tumor was defined as the highest GS tumor; in cases of multifocal tumors of identical GS, the largest tumor was considered the index. Chi-square or Fisher’s exact analysis was performed for categorical and t-test for continuous variables. RESULTS: 180 regions of interest were identified by mp-MRI and 283 tumors were histologically confirmed among 122 men. Among the 57 tumors determined to be GS 4+3, 15/57 tumors (26%) were missed by mp-MRI in 11/50 men (22%), corresponding to a sensitivity of 74%. Index tumor status, tumor size, number of whole mount levels involved, and presence of extra-capsular extension were all associated with tumor detection (p<0.05) (table). 37/44 (84%) of index tumors were correctly identified by mp-MRI. Missed tumors were: less likely to be index tumors (47% vs 88% of MRI-pathology concordant tumors); likely to be smaller (1.24 cm 0.78 cm SD vs 2.41 2.06 SD), involving fewer whole-mount levels; and less likely to have extra-capsular extension (13% vs 55%). Of missed non-index tumors, 4/8 (50%) of the corresponding index tumors were detected by mp-MRI. Of the missed index tumors, no corresponding non-index tumors were detected; review of these slides demonstrated tumor infiltrating benign glands (3/7), small volume tumor within large overall prostate volume (3/7), or abundant foamy gland variant pathology (2/7) as possible reasons for missed tumor detection. CONCLUSIONS: High Gleason score tumors evaded mp-MRI detection in 26% of cases. Smaller, non-index, organ-confined tumors were more likely to be missed; there may be a histologic basis for nonvisualization of tumors by mp-MRI. Table Characteristics of tumors missed versus detected by mp-MRI.

Low-grade, Low-stage Endometrioid Endometrial Adenocarcinoma

Patients with low-stage, low-grade endometrial adenocarcinomas have a favorable prognosis; however, a subset has a risk of recurrence and death. We were interested in evaluating patterns of myometrial invasion and correlating them with clinical outcome to potentially identify patients at increased risk. A total of 324 cases of low-stage Grade 1 endometrial adenocarcinoma were reviewed to identify those with myoinvasion. The myoinvasive cases were classified on the basis of the pattern of invasion: infiltrating glands, microcystic elongated and fragmented (MELF; a distinctive histologic variant of the infiltrative gland pattern), broad front, adenomyosis like, and adenoma malignum. Depth of invasion and lymphovascular invasion were recorded, and a clinical follow-up of at least 2 y was obtained, as most recurrences occur in this time frame. Ninety-eight of 324 (30%) cases were invasive; 75 had >2 y of follow-up, with an average length of follow-up of >7 y (range, 24-154 mo; mean 87 mo). All patients had a hysterectomy and bilateral salpingo-oophorectomy; 39 (52%) also underwent a lymphadenectomy. Twenty-seven (36%) were superficially invasive (<10% myoinvasion), 42 (56%) invaded 10% to 49%, and 6 (8%) invaded >50%. Six (8%) cases exhibited cervical stromal invasion (Stage II); the rest were Stage I (65 IA, 4 IB). The invasive patterns consisted of infiltrative glands (48; 65%), a broad front (16; 21%), MELF (5; 7%), adenomyosis like (5; 7%), and adenoma malignum like (1, 1%). There were 65 Stage 1A cases and, of these, the myoinvasive pattern was as follows: 41 infiltrating glands, 15 broad front, 5 MELF, and 4 adenomyosis like. There were 4 Stage IB cases, of which 2 had infiltrating glands, 1 had adenoma malignum, and 1 displayed adenomyosis-like invasion. Six (8%) cases had cervical stromal invasion (Stage II), of which 5 had an infiltrative pattern of growth and 1 displayed a broad front. Lymphovascular invasion was noted in 6 cases (8%), all of which had infiltrative glands. The majority of Grade 1 endometrioid endometrial adenocarcinomas do not invade the myometrium. In cases with invasion, the infiltrative gland pattern was associated with higher stage, (3/4 Stage IB, 5/6 Stage II), lymphovascular invasion (4/6 cases), and recurrence (2/75 cases), suggesting that this growth pattern may be associated with tumors having other histologic features typically associated with more aggressive behavior.

Cyclin D1 immunoreactivity in normal endocervix and diagnostic value in reactive and neoplastic endocervical lesions

It may be difficult to distinguish reactive glandular lesions from adenocarcinoma in situ of the uterine cervix, and although several immunohistochemical markers have established value in this diagnostic setting, none is completely reliable. We have noted that neoplastic endocervical lesions often show loss of nuclear cyclin D1 expression in contrast to benign glandular cells. Therefore, we investigated cyclin D1 staining in a series of 64 cervical biopsy specimens including examples of normal and reactive endocervical epithelium, adenocarcinoma in situ, stratified mucin-producing intraepithelial lesions, and invasive adenocarcinoma. Thirteen specimens also included a component of high-grade cervical squamous intraepithelial neoplasia. Normal endocervical epithelium usually expressed cyclin D1, although staining was typically focal, and there was increased immunoreactivity in reactive and metaplastic glandular cells including tubo-endometrioid metaplasia. In contrast, most cases of adenocarcinoma in situ were completely negative and, therefore, cyclin D1 staining distinguished benign from neoplastic epithelial cells. Although focal cyclin D1 expression was observed in 5/19 cases of adenocarcinoma in situ, the staining was associated with more marked cytological atypia precluding confusion with a reactive process. The invasive adenocarcinomas were mainly negative for cyclin D1. However, focal staining was observed in 10/19 cases and was mainly restricted to cells at the deep tumor margin, or to small infiltrative glands and detached cell clusters within the stroma. In conclusion, cyclin D1 can be included within an immunohistochemical panel to aid in the distinction between reactive cervical glandular lesions and adenocarcinoma in situ. The localized distribution of staining within invasive lesions suggests that cyclin D1 up-regulation has a specific role during the progression of some endocervical adenocarcinomas.

Combined hepatocellular and cholangiocarcinoma with sarcomatoid transformation: radiologic–pathologic correlation of a case

A 71-year-old man presented to our hospital with 3-week history of fever in the background of loss of both weight and appetite over the past 3months. He was found to have a large 10-cm mass in the right lobe of the liver on a triple-phase computed tomographic scan. The tumor showed a distinct fatty component, with areas of arterial enhancement and venous washout suggestive of hepatocellular carcinoma (HCC), another component showing progressive and late enhancement suggestive of cholangiocarcinoma (CC), and a third component showing persistent hypoenhancement relative to the liver parenchyma. He underwent surgical resection. This was histopathologically a biphasic tumor composed of areas showing hepatocytic differentiation, in contiguity with areas showing infiltrative glands set within fibrous stroma in keeping with combined hepatocellular and cholangiocarcinoma (cHCC-CC). A third component of pleomorphic spindle and epithelioid appearance in keeping with sarcomatous transformation was also found intimately related to the CC component. The patient developed extensive thoracic and abdominal metastases 2months after surgery and died shortly after.

The Role of CD10 Staining in Distinguishing Invasive Endometrial Adenocarcinoma from Adenocarcinoma Involving Adenomyosis

Adenomyosis may be involved by endometrial adenocarcinoma, but in contrast to true myometrial invasion, the depth of an adenomyotic focus involved by carcinoma does not alter pathologic tumor staging. Therefore, distinction from carcinoma invading myometrium is clinically relevant. We hypothesized that CD10, a marker of non-neoplastic and neoplastic endometrial stroma, would highlight the stromal component of adenomyotic foci and be useful in this distinction. Thirty-nine cases of endometrial adenocarcinoma were analyzed and divided into three groups: I, invasive endometrial adenocarcinoma (n = 14); II, endometrial adenocarcinoma involving adenomyosis but without myometrial invasion (n = 18); and III, adenomyosis involved by endometrial adenocarcinoma with concomitant invasive component (n = 7). All cases of adenomyosis involved by endometrial adenocarcinoma demonstrated CD10 expression in the stromal cells of adenomyotic foci. Eleven of 21 cases (52%) of invasive adenocarcinoma also showed CD10 expression, at least focally, in cells immediately surrounding the infiltrating glands. Of these, two cases (from Group III) also had associated adenomyotic involvement by carcinoma. The remaining cases of invasive carcinoma were negative for CD10. Therefore, presence of CD10 staining immediately surrounding neoplastic glands does not equate with involvement of adenomyosis by endometrial adenocarcinoma. In contrast, absence of CD10 expression excludes involvement of adenomyosis by adenocarcinoma.

Prostatic tissue in mature cystic teratomas of the ovary: a report of four cases, including one with features of prostatic adenocarcinoma, and cytogenetic studies.

Four cases of mature cystic teratoma that contained prostatic tissue are reported. The ovarian tumors occurred in patients from 17 to 38 (mean 31) years of age and had no unusual clinical or gross aspects. The microscopic findings for the most part were typical of a mature cystic teratoma, but they also contained foci of prostatic tissue that ranged from 0.2 to 1.9 cm in greatest dimension. In these areas there was a lobular arrangement of medium-sized acini lined by cuboidal to columnar cells with pale cytoplasm and round nuclei with inconspicuous nucleoli except focally in one case as noted below. Basal cells were seen focally. The prostatic acini lay in a paucicellular fibromuscular stroma. In two cases thick layers of disorganized smooth muscle covered by transitional-like pseudostratified epithelium, resulting in an appearance resembling fetal bladder wall, were present next to the prostatic glands. One tumor also contained prostatic-type acini, which haphazardly infiltrated the stroma over an area approximately 5 mm in maximal dimension. The acini, a few of which contained intraluminal flocculent eosinophilic material, were lined by cells with eosinophilic to amphophilic focally granular cytoplasm and had nuclei that were enlarged compared with the benign-appearing, prostatic-type acini in the four cases and had focally prominent nucleoli. Basal cells were not identified in these infiltrating glands. Grading this focus according to the approach in the prostate, the morphology was that of a Gleason grade 3 of 5 adenocarcinoma. Immunohistochemical stains of the putative prostatic epithelial cells confirmed their nature by showing immunoreactivity for prostatic-specific antigen in the lining epithelial cells in all four cases and for prostatic-specific acid phosphatase in the one case tested. The high molecular cytokeratin stain, 34betaE12, highlighted basal cells to a variable extent in the three cases containing only benign prostatic tissue. Material was not available to immunostain for basal cells in the case with carcinoma. Cytogenetic studies were performed in two cases and showed that the great majority of the nuclei of the nonprostatic and prostatic tissue had an XX karyotype but from 3% to 5% of the nuclei displayed trisomy for the X chromosome. A small number of cases of prostatic tissue in ovarian teratomas have previously been documented but none had morphologic features of carcinoma.

The myoepithelial immunophenotype in 135 benign and malignant salivary gland tumors other than pleomorphic adenoma.

We have previously studied the immunoreactivity of 3 novel smooth muscle-specific proteins, alpha-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas. To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors. Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat-induced epitope retrieval. In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer. Immunoreactivity for these 3 smooth muscle-specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.

Prostatic carcinoma with abundant xanthomatous cytoplasm. Foamy gland carcinoma.

Foamy gland carcinoma, an unusual variant of prostate carcinoma, is characterized by abundant xanthomatous cytoplasm. We studied 38 needle biopsies in which at least one core contained cancer with >20% foamy morphology. On average, each cancer was 72% foamy, and 11 cancers were entirely foamy. In addition to the characteristic cytoplasm, 20 cases had abundant intraluminal dense pink amorphous secretions. Nuclear enlargement and prominent nucleoli were either absent of rare in 23 (61%) and 27 (71%) of foamy gland carcinomas, respectively. High-molecular-weight cyto-keratin stains were done in 20 cases; 19 foamy gland carcinomas were negative, confirming the diagnosis of carcinoma and one case had keratin staining inconsistent with a known benign pattern. Of the 27 cases with associated ordinary gland carcinoma on needle biopsy, 26 (96%) were Gleason sum greater than 4. Subsequent radical prostatectomy (RP) and transurethral resection demonstrating cancer were available in 17 cases. Of the 15 subsequent RPs, only five were organ-confined and only one was Gleason sum less than 5. The cancers in the RP group ranged from 1 to 90% foamy (mean, 39%). Foamy gland carcinoma must be recognized as carcinoma by its abundant foamy cytoplasm, its architectural pattern of crowded or infiltrative glands, and frequently present pink acellular secretions. The more typical features of adenocarcinoma, nuclear enlargement and prominent nucleoli, are frequently absent. Its relatively benign cytology makes this lesion difficult to recognize as carcinoma; 74% of our cases were seen in consultation. Despite its benign cytology, foamy gland carcinoma is best classified as intermediate-grade carcinoma.

Gland cell carcinoma (adenocarcinoma) of the uterine cervix

1.1. Biopsies of uterine cervices during a period of approximately 22 years revealed 237 gland cell carcinomas; 127 (53.6 per cent) were primary in the cervix arising from glands or surface epithelium or both.2.2. The majority (30.8 per cent) of secondary carcinomas represented extension from the endometrium. Other primary sites were, in order of decreasing frequency, the ovary, colon and rectum, breast, and urinary tract.3.3. Ten examples of noninfiltrative gland cell carcinoma were encountered. Three of these represented in situ change in endocervical glands and in one instance there was also a squamous cell carcinoma in situ. Seven lesions consisted of carcinomatous change in endocervical polyps without infiltration of the cervix proper.4.4. The primary infiltrative gland cell carcinomas (110 cases) comprised 5.5 per cent of all infiltrative carcinomas arising in the uterine cervix.5.5. The average age of the patients with infiltrative gland cell carcinoma of the cervix was 53 years, with a range of 21 to 76 years. The average age for squamous cell carcinoma was 47 years and for gland cell carcinoma of the endometrium 59 years.6.6. The gestational histories of patients with primary gland cell carcinoma of the cervix were more closely allied to those of patients with endometrial carcinoma than to those with squamous cell carcinoma. The symptoms resembled those for squamous cell carcinoma but the duration of symptoms was appreciably longer.7.7. Structural and cytologic features permitted the recognition of distinctive patterns of growth in gland cell carcinoma of the cervix: adeniform, medullary, muciferous, papillary, acanthoid, and scirrhous. Two carcinomas in young women were of mesonephric origin.8.8. In situ change at the margins of infiltrative carcinomas was an important criterion in assigning origin to the cervix and was found in 43 per cent of cases.9.9. The majority of patients with gland cell carcinoma of the cervix were treated with radiation in a manner employed for squamous cell carcinoma of the cervix. The over-all 5 year survival rate for gland cell carcinoma was 29.9 per cent as compared with 40.1 per cent for squamous cell carcinoma and 54.3 per cent for gland cell carcinoma of the endometrium.10.10. A definite correlation was found between histologic pattern of growth and survival. The best results occurred with papillary carcinoma (57 per cent), followed by adeniform (30 per cent), muciferous (20 per cent), and medullary (14 per cent). The poorest prognoses were observed for acanthoadenocarcinoma (9 per cent) and scirrhous type (0 per cent).11.11. In 7 patients with primary infiltrative gland cell carcinoma of the cervix, there were second separate and distinct carcinomas in the uterus; 5 patients had infiltrative squamous cell carcinoma of the cervix and 2 had gland cell carcinoma of the endometrium. Six of these were synchronous and one metachronous.