Syringocystadenoma Papilliferum of the Anogenital Area and Buttocks: A Report of 16 Cases, Including Human Papillomavirus Analysis and HRAS and BRAF V600 Mutation Studies.

Syringocystadenoma papilliferum (SCAP) is a benign tumor most commonly located on the head and neck area often associated with nevus sebaceus. In its usual location, the human papillomavirus (HPV) DNA and mutations in the RAS/mitogen-activated protein kinase signaling pathway have been detected in SCAP. We studied 16 cases of SCAP in the anogenital areas and buttock where this neoplasm is rare and attempted to find out whether SCAP in these sites have different histopathological and molecular biological features. It seems that there is no significant difference between the morphology of anogenital SCAP and SCAP in other locations. Several tumors in our cohort demonstrated features resembling those seen in warts, but HPV DNA was not found in these lesions. On the contrary, we identified DNA of HPV high-risk types in some tumors without HPV-related morphology. Our study confirms the role of HRAS and BRAF V600 mutations in the pathogenesis of SCAP, including SCAP in the anogenital areas and buttock.

Esophageal dysplasia and adenocarcinoma: a study with double immunostaining for intestinal and gastric markers.

Columnar lined esophagus is a complication of long term gastroesophageal reflux disease and the main precursor of esophageal adenocarcinoma. Incomplete intestinal metaplasia in reflux esophagitis represents one of the most important risk factors for neoplastic transformation through the metaplasia-dysplasia-adenocarcinoma sequence. However, recent studies suggest that cardiac type mucosa also shows molecular abnormalities which are similar to those of incomplete intestinal metaplasia. Immunohistochemically, three types of esophageal dysplasia and adenocarcinoma are recognized: adenomatous-intestinal, hybrid/mixed and foveolar gastric types. We are interested in the phenotypes of these dysplasias and adenocarcinomas, especially in the possible relationship between them. For this reason, we evaluated the immunohistochemical expression of intestinal and gastric markers in a series of 30 cases of esophageal high-grade dysplasia (high-grade intraepithelial neoplasia) and of 70 adenocarcinomas. For immunohistochemical classification, we used double immunohistochemical reactions CDX2/MUC5AC and CDX2/MUC6, respectively. In cases of incomplete intestinal metaplasia, hybrid/mixed high-grade dysplasia and hybrid/mixed adenocarcinoma, we found the expression of gastric mucins MUC5AC and MUC6 only in cells with intestinal differentiation (with nuclear positivity for CDX2). The double immunostaining excluded the presence of the cells with "pure" foveolar gastric phenotype in hybrid lesions. Thus, the hybrid category actually represents the intestinal type dysplasia/adenocarcinoma (which is known to have a better prognosis than the foveolar gastric type). Keywords: immunohistochemistry - double immunostaining - reflux esophagitis - Barrett esophagus - esophageal dysplasia - esophageal adenocarcinoma.

Sinonasal SMARCB1 (INI1) Deficient Carcinoma With Yolk Sac Tumor Differentiation: Report of a Case and Comparison With INI1 Expression in Gonadal Germ Cell Tumors.

SMARCB1 (INI1) deficient sinonasal carcinoma is a recently recognized entity with wide histomorphologic spectrum. We present a case of this carcinoma that contained, in addition to a "common" morphology, scattered foci of yolk sac tumor differentiation. The tumor occurred in paranasal sinuses in a 44-year-old woman. Immunohistochemically, it was diffusely negative for INI1, whereas an expression of yolk sac tumor markers (α-fetoprotein, glypican-3, CDX2) was limited to the yolk sac tumor component. For comparison with the present case, we performed INI1 immunostaining on a series of 11 gonadal germ cell tumors with yolk sac tumor differentiation. All of these cases showed strong and diffuse expression of INI1, in contrast with the present sinonasal tumor. Our findings expand the morphologic spectrum of SMARCB1 (INI1) deficient sinonasal carcinoma. In addition, we show preliminarily that gonadal germ cell tumors with yolk sac tumor differentiation are not SMARCB1/INI1-deficient.

Basal Cell Carcinoma With Matrical Differentiation: Clinicopathologic, Immunohistochemical, and Molecular Biological Study of 22 Cases.

Basal cell carcinoma (BCC) with matrical differentiation is a fairly rare neoplasm, with about 30 cases documented mainly as isolated case reports. We studied a series of this neoplasm, including cases with an atypical matrical component, a hitherto unreported feature. Lesions coded as BCC with matrical differentiation were reviewed; 22 cases were included. Immunohistochemical studies were performed using antibodies against BerEp4, ß-catenin, and epithelial membrane antigen (EMA). Molecular genetic studies using Ion AmpliSeq Cancer Hotspot Panel v2 by massively parallel sequencing on Ion Torrent PGM were performed in 2 cases with an atypical matrical component (1 was previously subjected to microdissection to sample the matrical and BCC areas separately). There were 13 male and 9 female patients, ranging in age from 41 to 89 years. Microscopically, all lesions manifested at least 2 components, a BCC area (follicular germinative differentiation) and areas with matrical differentiation. A BCC component dominated in 14 cases, whereas a matrical component dominated in 4 cases. Matrical differentiation was recognized as matrical/supramatrical cells (n=21), shadow cells (n=21), bright red trichohyaline granules (n=18), and blue-gray corneocytes (n=18). In 2 cases, matrical areas manifested cytologic atypia, and a third case exhibited an infiltrative growth pattern, with the tumor metastasizing to a lymph node. BerEP4 labeled the follicular germinative cells, whereas it was markedly reduced or negative in matrical areas. The reverse pattern was seen with ß-catenin. EMA was negative in BCC areas but stained a proportion of matrical/supramatrical cells. Genetic studies revealed mutations of the following genes: CTNNB1, KIT, CDKN2A, TP53, SMAD4, ERBB4, and PTCH1, with some differences between the matrical and BCC components. It is concluded that matrical differentiation in BCC in most cases occurs as multiple foci. Rare neoplasms manifest atypia in the matrical areas. Immunohistochemical analysis for BerEP4, EMA, and ß-catenin can be helpful in limited biopsy specimens. From a molecular biological prospective, BCC and matrical components appear to share some of the gene mutations but have differences in others, but this observation must be validated in a large series.

Small Cell Carcinoma of the Ovary (Hypercalcemic Type): Malignant Rhabdoid Tumor.

We present a rare case of malignant rhabdoid tumor (ovarian small cell carcinoma of hypercalcemic type) in a 24-year-old female with fulminant course. Clinically, hypercalcemia was not found at the time of primary diagnosis. However, it appeared later during the course of tumor progression. Histologically, the tumor showed classical features of small cell carcinoma of hypercalcemic type. Therapy included radical surgery with adjuvant chemotherapy. Despite this intensive therapy, the disease recurred and the patient died 10 months after the diagnosis. We discuss the diagnosis and therapy of this tumor, as well as its recent classification as malignant rhabdoid tumor.

[Serrated adenomas and carcinomas of the colon]. / Serrated adenomy a karcinomy tlustého streva.

Approximately 5 - 35 % of colorectal carcinomas arise through serrated carcinogenesis. The precursor of such carcinomas are serrated adenomas, which differ from conventional adenomas morphologically as well as genetically. Herein, we provide a basic overview of serrated lesions of the large intestine with the focus on histological diagnosis and molecular biology.

Hidradenoma Papilliferum: A Clinicopathologic Study of 264 Tumors From 261 Patients, With Emphasis on Mammary-Type Alterations.

Hidradenoma papilliferum (HP), also known as papillary hidradenoma, is the most common benign lesion of the female anogenital area derived from anogenital mammary-like glands (AGMLG). HP can be viewed conceptually as the cutaneous counterpart of mammary intraductal papilloma. The authors have studied 264 cases of HP, detailing various changes in the tumor and adjacent AGMLG, with emphasis on mammary-type alterations. In many HP, the authors noticed changes typical for benign breast lesions, such as sclerosing adenosis-like changes, usual, and atypical ductal hyperplasia. Almost in a third of cases, remnants of AGMLG adjacent to the lesion were evident, manifesting columnar changes reminiscent of those seen in breast lesions. This study shows that the histopathological changes in HP run a broad spectrum comparable with that in the mammary counterpart and benign breast disease.

Shadow cell differentiation in endometrioid carcinomas of the uterus. Its frequent occurrence and beta-catenin expression.

Shadow cell differentiation (SCD) is typical for pilomatrixoma and related follicular tumors of the skin. However, it has been described rarely in some extra-cutaneous lesions such as gonadal teratoma, craniopharyngioma, odontogenic cyst, and in rare visceral carcinomas (lung, bladder, gallbladder, uterus, ovary, and colon). In our practice, we have noticed that the occurrence of shadow cells is not very rare in endometrioid carcinoma (EC) of the uterus. For exact determination of SCD in these tumors, we reviewed 59 consecutive cases of uterine EC. The series included curettage and hysteroscopic specimens. We have found SCD in 9 (15.3 %) of the tumors. In these cases, the age of the patients and FIGO grade did not differ significantly from other ECs. Immunohistochemically, all ECs with SCD showed nuclear expression of beta-catenin in areas of SCD, indicating a possible role of the Wnt signaling pathway in tumorigenesis as well as a role of nuclear accumulation of beta-catenin by trans-differentiation from glandular toward squamous and shadow cell phenotypes. We have found that the relatively frequent presence of SCD in ECs can assists in the diagnosis of these tumors.

Pyloric gland adenoma: a histologic, immunohistochemical and molecular genetic study of 23 cases.

Pyloric gland adenoma is a rare neoplasm with a gastric epithelial differentiation. We report 23 cases of pyloric gland adenoma in older persons, with a mean age of 74 years (range 52 - 87 years). They occurred in the esophagus (3 cases), corporal gastric mucosa (7 cases), duodenum (10 cases), gallbladder (2 cases), and choledochus (one case). Histologically, they were characterized by closely packed pyloric gland-type tubules with a monolayer of cuboidal to low columnar epithelial cells containing basally located round nuclei, and a superficial layer of tall, columnar, foveolar-type epithelium. Immunohistochemically, most tumor glands expressed pyloric gland mucin MUC6, whereas MUC5AC was positive in superficial gastric foveolar epithelium, and in a minority of glands. In addition, scattered neuroendocrine cells positive for chromogranin A and/or synaptophysin were seen in all cases. In 3 cases (two cases in the gallbladder and one case in the esophagus), areas of intestinal metaplasia with CK20, CDX2, and MUC2 positivity were found. Focal low-grade dysplasia was found in five cases (21.7%), and diffuse high-grade dysplasia was seen in one adenoma (4.4%), i.e., 6 of 23 PGAs (26.1%) showed dysplastic features. In one esophageal case, an invasive adenocarcinoma was diagnosed. Scattered p53 positive cells were found in all cases. Their number was higher in lesions with low-grade dysplasia and it was substantially increased in adenoma with high-grade dysplasia and in adenocarcinoma. Our molecular genetic results indicate that pyloric gland adenomas neoplastic nature is associated with p53 accumulation, mutations in oncogenes GNAS, KRAS, CTTNB1 and tumor suppressor genes SMAD4, and TP53. Pyloric gland adenoma can evolve into dysplasia and adenocarcinoma.

Intestinal metaplasia of the stomach and esophagus: an immunohistochemical study of 60 cases including comparison with normal and inflamed intestinal mucosa.

Recently, a new classification of intestinal metaplasia (IM) using immunohistochemical mucin markers was proposed. Two following types of IM were defined: (1) a mixed gastric and intestinal type also called incomplete IM; (2) a purely intestinal type, also called complete IM. We present a series of 30 cases of gastric IM and 30 cases of IM of the esophagus, using this new classification. In all gastric cases, IM developed in the mucus-neck region in the form of incomplete IM. Toward the mucosa surface, it matured gradually into complete IM. This maturation showed a gradual reduction of both foveolar mucin MUC5AC and pyloric gland mucin MUC6. In two of 30 cases, IM was of the incomplete hyperproliferative type. In one case, focal high-grade adenomatous dysplasia was found in the incomplete IM. In the esophageal cases, IM was found in inflamed cardiac-type mucosa, and it was usually of the incomplete type, with almost diffuse positivity for MUC5AC and with rare positivity of MUC6. The goblet cells and some cylindrical cells expressed intestinal mucin MUC2. The proliferation was higher than in the complete IM, and in one case, focal low grade adenomatous dysplasia was found. In addition, we examined the expression of mucins in normal and inflamed intestinal mucosa. These cases included 50 duodenal biopsies, 50 biopsies from the ileum, and 50 biopsies from the colon. The inflamed cases included celiac disease, Crohn's disease, and ulcerative colitis. Some goblet cells of the normal intestinal mucosa expressed both MUC2 and MUC5AC. More numerous MUC5AC+ goblet cells were found in the inflamed intestinal mucosa. In the duodenal and small intestinal mucosa, even the MUC6 positivity of a few goblet or cylindrical cells was found. In sum, our results indicate that incomplete IM is an initial step of the metaplastic process. It can mature into complete IM, or alternatively, it can develop dysplasia or adenocarcinoma. In addition, we found that gastric-type mucins are also present in normal or inflamed intestinal mucosa, and that the expression of these mucins is even enhanced in some inflammatory conditions. The expression of MUC5AC in complete IM and in normal or inflamed mucosa suggests that MUC5AC cannot be regarded as a marker of immaturity. In Barrett esophagus, our results were similar to those of previous studies, except for CDX2 of which reactivity was seen also in incomplete type of IM.

Ovarian basaloid carcinoma with shadow cell differentiation.

So-called shadow cell differentiation (SCD) is typical for pilomatrixoma and other skin lesions with follicular differentiation, but it was rarely described also in some visceral carcinomas. We report a case of ovarian basaloid carcinoma with SCD. The tumor presented as a 14 cm ovarian mass in a 45-year-old woman, and therefore the adnexectomy and hysterectomy were performed. The tumor was of high stage. Multiple metastases were found in the liver, retroperitoneal and mediastinal lymph nodes, and the lung. Histologically, the tumor showed a pattern of high-grade basaloid carcinoma with numerous shadow cells. Extensive histologic examination did not reveal any glandular or preexisting teratoma component. Immunohistochemically, the tumor expressed markers of squamous cell differentiation, such as p63, cytokeratin 5/6, and high-molecular-weight keratin. Cytokeratin 7 and CA125 were positive in scattered cells of the lesion. Estrogen and progesterone receptor, vimentin, and p53 were negative. Beta-catenin showed nuclear and cytoplasmic positivity, indicating possible tumor proliferation/differentiation via Wnt signaling pathway. To our knowledge, SCD in basaloid carcinoma of the ovary was not described before. In addition to the description of the case, we review the literature on SCD in visceral carcinomas.

Endometriosis in a mesothelial cyst of tunica vaginalis of the testis. Report of a case.

A rare case of endometriosis occurring in paratesticular mesothelial cyst is presented. It was found in a 7 mm mesothelial inclusion cyst of tunica vaginalis in a 46-years-old old man who underwent a radical orchiectomy for seminoma. It showed a typical histologic pattern with endometrioid cylindrical epithelium and cellular stroma. The lesion was immunohistochemically positive for estrogen receptors and progesterone receptors, in contrast with the adjacent mesothelium. However, rare endometrioid epithelial cells expressed mesothelial markers calretinin and cytokeratin 5/6. This immunohistochemical overlap with mesothelium and morphological transition between endometrioid epithelium and mesothelium favor metaplastic pathogenesis of the lesion. In differential diagnosis, it is important to distinguish paratesticular endometriosis from tissue of teratoma (especially when a germ cell tumor is present in the testis, as was seen in this case).

Angiofibroma-like perineurioma. Report of a case.

We report an unusual perineurioma with numerous vessels, showing a strong similarity with angiofibroma. A 2,5 x 2 x 2 cm subcutaneous/dermal tumor occurred in 58-ys-old male in the left brachial region. Histologically, it was composed of haphazardly arranged bland spindle cells and it contained prominent vasculature. In rare foci, the tumor cells showed thin bipolar processes and an onion-like perivascular whorling pattern. Immunohistochemically, expression of perineural cell markers EMA, claudin-1 and CD34 was limited to perivascular foci and to rare cells among the vessels. In addition, the tumor expressed CD10 diffusely. Our finding indicates that diagnosis of perineurioma should be considered also by tumors with an "angiofibromatous" morphology. Especially soft tissue angiofibroma, which often express EMA (perineural cell marker), shows a strong resemblance to angiofibroma-like perineurioma.

Gastric dysplasias. A clinicopathological study of 35 cases.

Gastric epithelial dysplasia (GED) represents a recognized precursor lesion of gastric adenocarcinoma. GED types can be classified according to its morphology and patterns of mucin expression into adenomatous (intestinal), foveolar (gastric) and hybrid (mixed) types. We examined gastroscopic specimens with GED in 35 patients (21 men and 14 women, mean age 69.6 years). Adenomatous dysplasia was present in 17 patients (49 %), and was of low grade in 14 cases and high grade in 3 cases. Foveolar type dysplasia was found in 16 patients (46 %), and almost in one half of the cases it was high grade (in 7 cases, i.e. 46 %). In one woman, low grade foveolar dysplasia was found in polypoid mucosal prolapse of the gastric antrum. Hybrid dysplasia was found in only 2 cases (0.6 %), and in both of them this dysplasia was predominantly of foveolar type. One case was of low-grade and the second case was of a high-grade type. In our series GED was found mostly in the antrum. The findings in the adjacent mucosa usually included HP negative inactive chronic gastritis with intestinal metaplasia of both complete and incomplete types. In our series, foveolar type dysplasia was more frequent in comparison with previous studies. Our findings show that high grade dysplasia is more frequent in foveolar GD than in adenomatous GD, and this is in keeping with previous published findings.

Mitotically active deep juvenile xanthogranuloma.

Juvenile xanthogranuloma is a relatively rare cutaneous tumor of histiocytic origin, occurring mainly in neonates, children, and young people in the first 2 decades of life. An occurrence in adults is rare. Very rare is also a "deep" subcutaneous and intramuscular localization of this tumor that is called in such case as "deep juvenile xanthogranuloma." A very uncommon variant of this tumor is the so-called mitotically active xanthogranuloma, which was described in the literature only in a single case. We present an interesting case of the mitotically active intramuscular juvenile xanthogranuloma of the upper arm in a 28-year-old woman. Before surgical excision, the tumor was examined by fine-needle aspiration biopsy. A diagnosis of deep malignant melanoma or alveolar rhabdomyosarcoma was considered. One year after the total excision, the patient is free of disease. In the presented case, we emphasize cytologic-histologic correlation. In the differential diagnosis, we considered especially an atypical diffuse giant cell tumor of tendon sheaths and joints (extra-articular pigmented villonodular synovitis) and some rare types of soft tissue leiomyosarcoma, such as epitheloid leiomyosarcoma and leiomyosarcoma with prominent osteoclast-like giant cells.

Low-grade sarcoma in classical seminoma - the first case reported.

A 30-year-old male with no previous history of neoplastic disease presented with a 5 cm large testicular tumor. Routine histopathological examination and immunohistochemical investigation showed a classical seminoma with a contiguous 8 mm large nodule. The nodule was separated from the tunica albuginea by tubuli seminiferi showing intratesticular germ cell neoplasi not otherwise specified (NOS). The nodule was composed of spindle cells with low-grade nuclear atypia, nuclear and cytoplasmic S100 protein immunoreactivity in 15% of the cells and a proliferative activity of up to 20%. No other germ cell tumor components were found. To the best of our knowledge, we herein present the first tumor of a pure classical seminoma with an associated low-grade sarcomatous component.