Submucosal calcifying fibrous tumor of the stomach: A case report.

The calcifying fibrous tumor is a rare benign fibrous tumor which occurs in subcutaneous or deep soft tissues in children and young adults, but also is frequently seen in pleural and intraabdominal locations in older people. Gastric involvement has been only sporadically reported in the literature. We present here our experience with this unusual lesion discovered in a 68-year-old woman. Clinically, the tumor was described as a pendulating, submucosally located mass, in the body of the stomach on a lesser curvature. The calcifying fibrous tumor is a histologically distinct lesion composed of dense hyalinized collagen fibers, inconspicuous scattered fibroblasts, a varying amount of psammoma bodies or dystrophic calcifications and foci of lymphoplasmacytic infiltration. In this report we will focus on a brief review and differential diagnosis of this tumor and other more common or not widely known gastric spindle cell lesions.

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.

A novel germline mutation in the CYLD gene in a Slovak patient with Brooke-Spiegler syndrome.

The authors report a 64-year-old female with Brooke-Spiegler syndrome who presented with multiple cutaneous nodules and tumors mostly involving the scalp. Histopathological examination of one of the lesions located in a periauricular area revealed a typical cylindroma. In some neoplastic nodules ductal differentiation and occasional bilayered glands composed of the dark abluminal basal/myoepithelial cells and luminal mucinous cells might be recognized. Apocrine secretion was focally noted. Molecular biologic study of the CYLD gene performed from the peripheral blood identified a novel splice site c.2041+1 G>T mutation. This new germline mutation in the CYLD gene of a Slovak patient with Brooke-Spiegler syndrome extends the catalogue of known CYLD germline mutations in this condition.

Primary adenomyoepithelioma of the sellar region: a case report.

Small nests of an ectopic salivary gland tissue are clinically insignificant and they are an incidental finding at microscopic examination in various organs at autopsy. Intracranially, they are suggested to be the origin of extremely rare sellar tumors that bear a marked resemblance to tumors of the salivary gland. We report a case of 38-year-old man who presented with a sellar mass and partial visual loss. The tumor was surgically removed and microscopic examination showed a lesion consistent with adenomyoepithelioma as known in salivary gland pathology. After the surgery, the patient was administered substitution treatment for pan-hypopituitarism and diabetes insipidus. The neoplasm recurred 14 years after surgery in the same location. Transfrontal decompressive operation was followed by a transnasal procedure during which gross total removal of the tumor was achieved. The recurrent tumor displayed an identical morphology to the initial neoplasm; the only difference was an increase in the proliferative activity of the neoplastic cells in the recurrent growth. Six months after the surgery for the recurrent neoplasm, there are no clinical and radiological signs of tumor progression.

Carcinoid-like pattern in melanoma: report of 4 cases.

Cutaneous melanoma can produce a wide variety of unusual morphological appearances, sometimes mimicking other tumors. We report on 4 cases of melanoma with carcinoid-like features, namely, arrangement of neoplastic cells in trabecules, ribbons, pseudorosettes, rosettes, and/or small round islands. A total of 10 biopsies from 4 patients were available for a histopathological study comprising congenital nevus, a nodule that had developed in this nevus and its persistence/recurrence, 3 primary cutaneous lesions, 3 metastases, and a recurrent/persistent lesion. In 7 of these 10 lesions, the most characteristic finding was a distinctive arrangement of the neoplastic cells as trabecules, ribbons, pseudorosettes, rosettes, or small round insular islands, thus closely resembling cell arrangement in carcinoids of various organs. All these tumors were positive for melanocytic markers. No neuroendocrine differentiation was demonstrated immunohistochemically. We conclude that the carcinoid-like pattern in melanoma, namely, the pattern in which neoplastic cells are arranged in trabecules, ribbons, cords, rosettes, pseudorosettes, and small round insular nests resembling those in carcinoids, is a distinctive pattern, which may rarely occur in primary cutaneous melanoma, its recurrence or metastasis, or in a melanoma associated with a large congenital nevus. This morphological type of melanoma may produce a serious diagnostic pitfall, but despite a confusing microscopic appearance, these tumors seem to demonstrate a conventional immunohistochemical profile.

TSC2/PKD1 contiguous gene syndrome: a report of 2 cases with emphasis on dermatopathologic findings.

The association of tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD), termed TSC2/PKD1 contiguous gene syndrome, is a result of molecular defect demonstrating by deletion disrupting TSC2 and PKD1. Dermatopathology of this syndrome has never been addressed. We report 2 sporadic cases form of TSC2/PKD1 contiguous gene syndrome, with emphasis on dermatopathologic findings. Both patients presented with a typical phenotype of TSC and early-onset renal polycystic requiring kidney transplantation in one of the patients. Of a total of 13 cutaneous lesions studied, there were 7 facial angiofibromas, 2 shagreen patches, 1 periungual fibroma, 1 hypopigmented macule, 1 epidermoid cyst, and 1 intradermal melanocytic nevus. The histological features were basically similar to those occurring in TSC, but some unusual features were identified. In both patients, deletions in the region of TSC2 and PKD1 were revealed performing by multiplex ligation probe amplification test. It is concluded that the histopathological features of skin lesions in this syndrome are similar to those encountered in TSC. Clinical awareness and appropriate molecular investigation of TSC2/PKD1 contiguous gene syndrome is necessary in all patients with a typical phenotype of TSC in infancy, adolescence, or adult age, because of severity of the renal alterations.

Ovarian fibromas with heavy deposition of hyaline globules: a diagnostic pitfall.

SUMMARY: We report 5 patients with cellular ovarian fibromas, which contained heavy depositions of hyaline globules, a remarkable and very conspicuous histologic feature of all tumors. The hyaline globules ranged in size from 1 to 25 microm. Some cells were stuffed with myriads of small hyaline globules 1 to 3 microm in size, whereas in the other cells the globules were up to 25 microm in size. The hyaline globules were stained with periodic acid-Schiff, and were mucicarmine and Alcian blue negative. These hyaline globules were present, at least in small numbers, in all 100 hematoxylin and eosin slides reviewed from all 5 cases in this series. Often the cells containing the hyaline globules showed a signet-ring appearance in the more compact cellular areas. All the tumors in our series appear to have a benign course. The patients were without signs of recurrence and without metastasis 1, 2, 3, and 6 years after the excision of the neoplasms. Follow-up in one of the patients was not available. The distinction of the ovarian fibromas with hyaline globules from the Krukenberg tumors and yolk sac tumor is discussed in the paper.

Cutaneous hidradenocarcinoma: a clinicopathological, immunohistochemical, and molecular biologic study of 14 cases, including Her2/neu gene expression/amplification, TP53 gene mutation analysis, and t(11;19) translocation.

We present a series of 14 cases of cutaneous hidradenocarcinomas. The patients included 6 women and 8 men ranging in age at diagnosis from 34 to 93 years. All but 1 patient presented with a solitary nodule. There was no predilection site. One patient presented with multiple lesions representing metastatic nodules. Of 12 patients with available follow-up, 2 died of disease, whereas the remaining 10 patients were alive but 3 of them experienced a local recurrence in the course of the disease. Grossly, the tumors ranged in size from 1.2 to 6 cm. Microscopically, of the 14 primary tumors, 9 showed low-grade cytomorphology, whereas the remaining 5 neoplasms were high-grade lesions. The residuum of a hidradenoma was present in 5 of the 14 primaries. The mitotic rate was highly variable, ranging from 2 to 64 mitoses per 10 high-power field. The cellular composition of the tumors varied slightly, with clear cells, epidermoid cells, and transitional forms being present in each case. In 1 case, there was metaplastic transformation into sarcomatoid carcinoma. Glandular differentiation varied from case to case and appeared most commonly as simple round glands or as cells with intracytoplasmic lumens. Necrosis en masse was detected in 8 specimens. One specimen represented a reexcision and was unusual as it showed a well-demarcated intradermal proliferation of relatively bland clear cells accompanied by an overlying intraepidermal growth of clear cells resembling hidradenoacanthoma simplex. Despite the bland appearance, the tumor metastasized to a lymph node. Immunohistochemically, 5 of the 8 specimens studied for Her2/neu expression were negative, whereas 3 specimens from 2 cases yielded score +2, but all the 3 specimens with score 2+ subsequently proved negative for Her2/neu gene amplification by fluorescence in situ hybridization. Of 10 primaries studied, 4 tumors showed positive p53 immunoreaction in more than 25% of the cells comprising the malignant portion of the lesions, in 2 cases, a minority of the neoplastic cells (10%-20%) demonstrated nuclear staining, whereas the remaining 4 cases were negative. Of 9 specimens of hidradenocarcinoma studied for TP53 mutations, 2 harbored mutations, whereas the remaining 7 specimens showed the wild-type sequence. Of 11 specimens studied for translocation t(11;19), 2 cases harbored the translocation. It is concluded that cutaneous hidradenocarcinomas show some microscopic heterogeneity and comprise both low- and high-grade lesions that cytologically are similar to their benign counterpart, the hidradenoma. Within the spectrum of low-grade lesions, there seem to exist tumors almost indistinguishable from hidradenomas but still being capable of regional or distant metastasis. Similar to hidradenomas, hidradenocarcinomas show a t(11;19) translocation, but it is a significantly rarer event. Even rarer is the amplification of the Her2/neu gene. Of note is the relatively low frequency of TP53 mutations despite a high rate of p53 protein expression at the immunohistochemical level.

Morphologic diversity of malignant neoplasms arising in preexisting spiradenoma, cylindroma, and spiradenocylindroma based on the study of 24 cases, sporadic or occurring in the setting of Brooke-Spiegler syndrome.

The authors present a series of 24 malignant neoplasms arising in preexisting benign spiradenoma (20), cylindroma (2), and spiradenocylindroma (2). Nineteen patients (12 females, 7 males; age range, 41 to 92 y) had a solitary neoplasm (size range, 2.2 to 17.5 cm; median 4 cm), whereas the remaining 5 (4 females, 1 male; age range, 66 to 72 y) manifested clinical features of Brooke-Spiegler syndrome (BSS), an autosomal dominantly inherited disease characterized by widespread, small, benign neoplasms on which background larger malignant lesions appeared. Microscopically, all cases showed the residuum of a preexisting benign neoplasm. The malignant components of the lesions were variable and could be classified into 4 main patterns, occurring alone or in combination: 1) salivary gland type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG); 2) salivary gland type basal cell adenocarcinoma-like pattern, high-grade (BCAC-HG); 3) invasive adenocarcinoma, not otherwise specified (IAC-NOS); and 4) sarcomatoid (metaplastic) carcinoma. In 1 case of IAC-NOS, an in situ adenocarcinoma was also found, presumed to have evolved from an adjacent adenomatous and atypical adenomatous component. Cases harboring a sarcomatoid carcinoma featured a malignant epithelial component composed of varying combinations of BCAC-HG, BCAC-LG, IAC-NOS, or squamous cell carcinoma, whereas the sarcomatoid component appeared as either a pleomorphic or spindle-cell sarcoma. Additionally, in 2 cases there were foci of heterologous chondrosarcomatous differentiation and in 1 case there was rhabomyosarcomatous differentiation. Of the 21 patients with available follow-up (range, 3 mo-15 y; average 4.8 y; median 3.5 y), 10 were without evidence of disease, 1 was alive with metastatic disease, 1 was alive with BSS, 3 developed local recurrences, 4 had died of disease, and 2 were dead of other causes. The histologic pattern of the malignant neoplasm correlated to some extent with the clinical course. BCAC-LG neoplasms showed a less aggressive course, with local recurrences but no distant metastases, whereas the BCAC-HG neoplasms typically followed a highly aggressive course resulting in the death 3 of 6 patients with BCAC-HG. Patients with sarcomatoid carcinoma had a relatively good survival. Molecular genetic investigations revealed no mutations in the CYLD gene in the 4 sporadic cases investigated. One patient with BSS revealed a novel missense germline mutation in exon 14 (c. 1961T>A, p. V654E), whereas a living descendant of another deceased patient demonstrated a recurrent nonsense germline mutation in exon 20 (c. 2806C>T, p. R936X). Given the morphologic diversity and complexity of the neoplasms in question, we propose using a more specific terminology with the precise description of the neoplasm components, rather than generic and less informative terms such as "spiradenocarcinoma" or "carcinoma ex cylindroma."