The many faces and mimics of papillary thyroid carcinoma

This article provides an overview of the 15 histologic variants of papillary thyroid carcinoma listed by the 2004 World Health Organization (WHO) monograph on endocrine tumors. The histologic features, differential diagnosis, and clinical course of each variant are discussed in some detail. The follicular variants (conventional and macrofollicular) constitute a morphologic challenge because the majority of these tumors are encapsulated and, also, because, in many tumors, not all neoplastic cells show the nuclear features considered to be diagnostic of papillary carcinoma. As a result, most of these tumors are missed even by experienced pathologists. Moreover, hyperplastic thyroid lesions, follicular adenomas, and Hashimoto’s thyroiditis may contain cells with clear nuclei resembling those of papillary carcinoma. Papillary carcinomas composed entirely of hyperchromatic cells have been overlooked. The WHO monograph defines papillary carcinoma with focal spindle and giant cell carcinoma components but its clinical behavior is unknown. Papillary carcinoma with an insular pattern that does not show the artifactual separation of the cell nests has been misinterpreted as the solid variant of papillary carcinoma. Papillary microcarcinomas include not only the conventional type and the follicular variants but also the tall cell and columnar cell variants.     

Spezifische Typen des Harnblasenkarzinoms

Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo–)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review.     

Endometriale Karzinome und Vorstufen – Neue Aspekte

Endometrial carcinomas can be separated into two groups which are designated as type I and type II carcinomas today. Both groups of tumors are clearly different with regard to conventional light microscopy, immunohistochemistry, molecular pathology and clinical features. Only type I carcinomas are associated with hyperestrogenism. The group of type I carcinomas consists of endometrioid carcinoma and its variants, and mucinous carcinoma. The prototypes of type II carcinomas are serous and clear cell carcinoma. Not all carcinomas, however, can be assigned to one of the two groups, because there are hybrid tumors and mixed carcinomas, e.g. endometrioid carcinoma with a serous component. The precursor lesions of the endometrioid carcinoma and the serous carcinoma are well characterized morphologically and by molecular pathology. Atypical hyperplasia is the precursor lesion of endometrioid carcinoma, whereas endometrial intraepithelial carcinoma (EIC) is the precursor lesion of serous carcinoma. No precursor lesion has as yet been identified for clear cell carcinoma. Immunohistochemical markers for endometrial carcinoma are CK7 and vimentin, for serous carcinoma markers are p53 and p16. Correct typing is of essential prognostic necessity in endometrial carcinoma. Of utmost importance is the detection of a serous component, because serous carcinoma leads to early tumor spread with the necessity of radical surgery, chemotherapy and radiotherapy.     

Sarcomatoid carcinoma (so-called pseudosarcoma) of the larynx simulating malignant giant cell tumor of soft parts. A case report

A tumor of the larynx composed of a small infiltrating and well-differentiated squamous cell carcinoma and a large polypoid sarcomatous mass showing the histologic features of the malignant giant cell tumor of soft parts (MGCT) is reported. Other types of sarcomatous components have been described with squamous cell carcinoma (SCC) of the larynx and names such as pseudosarcoma, carcinosarcoma, and spindle cell carcinoma have been used for these peculiar tumors. Because most data support that the sarcomatous component is an unusual carcinoma transformation due to unknown factors the authors prefer the term sarcomatoid carcinoma. Sarcomatoid carcinomas having the features of MGCT have been described in multiple epithelial organs. Therefore, an extensive search for a carcinoma component always should be carried out in tumors arising in any organ, including the larynx, and showing the typical histologic features of MGCT.     

Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis

The pathogenesis of ovarian carcinoma, the most lethal gynecological malignancy, is unknown because of the lack of a tumor progression model. Based on a review of recent clinicopathological and molecular studies, we propose a model for their development. In this model, surface epithelial tumors are divided into two broad categories designated type I and type II tumors that correspond to two main pathways of tumorigenesis. Type I tumors tend to be low-grade neoplasms that arise in a stepwise manner from borderline tumors whereas type II tumors are high-grade neoplasms for which morphologically recognizable precursor lesions have not been identified, so-called de novo development. As serous tumors are the most common surface epithelial tumors, low-grade serous carcinoma is the prototypic type I tumor and high-grade serous carcinoma is the prototypic type II tumor. In addition to low-grade serous carcinomas, type I tumors are composed of mucinous carcinomas, endometrioid carcinomas, malignant Brenner tumors, and clear cell carcinomas. Type I tumors are associated with distinct molecular changes that are rarely found in type II tumors, such as BRAF and KRAS mutations for serous tumors, KRAS mutations for mucinous tumors, and beta-catenin and PTEN mutations and microsatellite instability for endometrioid tumors. Type II tumors include high-grade serous carcinoma, malignant mixed mesodermal tumors (carcinosarcoma), and undifferentiated carcinoma. There are very limited data on the molecular alterations associated with type II tumors except frequent p53 mutations in high-grade serous carcinomas and malignant mixed mesodermal tumors (carcinosarcomas). This model of carcinogenesis reconciles the relationship of borderline tumors to invasive carcinoma and provides a morphological and molecular framework for studies aimed at elucidating the pathogenesis of ovarian cancer.     

Grading von Tumoren der Kopf‑Hals‑Region

Tumors of the head and neck form a heterogeneous group of benign and malignant neoplasms with significant differences in biological behavior and therapeutic strategies. Squamous cell carcinomas (SCC) of the larynx, pharynx and oral cavity represent the most frequent and, thus, clinically most important malignant neoplasms in this anatomical region. Similar to other neoplasms, grading of head and neck malignancies is based on evaluation of the tumor histology usually including both architectural and cytological features; however, the current consensus grading for head and neck SCC is of limited prognostic and therapeutic value and the reproducibility is low. Therefore, novel grading criteria have been proposed that are based on additional parameters, such as the type of tumor growth pattern at the invasive front (so-called tumor budding). These novel algorithms, however, have not yet been officially endorsed into guidelines. Salivary gland (SG) neoplasms, although less frequent, constitute a second important pathologically and clinically complex group of tumors at this location. In contrast to SCC, grading of these tumors is of high clinical importance. Based on the large variety of carcinoma entities of the SG, both entity-specific (e.?g. mucoepidermoid carcinoma) algorithms but also algorithms, which are solely based on the recognition of a specific carcinoma variant with subsequent automatic assignment of the tumor grade (e.?g. acinic cell carcinoma and salivary duct carcinoma) are in use. In the sinonasal tract, grading is important for non-intestinal type adenocarcinoma and esthesioneuroblastoma. In this article the most important grading schemes and criteria for head and neck malignancies are presented and their prognostic and therapeutic implications are discussed.     

Histologic classification of penile carcinoma and its relation to outcome in 61 patients with primary resection

A retrospective review of the clinical and pathologic features of 61 cases of penile squamous cell carcinoma (SCC), all treated by primary surgical resection at the Memorial Sloan Kettering Cancer Center during the period 1949-1992, was undertaken. Inguinal lymph node dissection material was evaluated in 40 cases. All carcinomas were of squamous cell type and were classified as follows: usual type, 36 cases (59%); papillary, not otherwise specified (NOS), 9 cases (15%), basaloid, 6 cases (10%); warty (condylomatous), 6 cases (10%); verrucous, 2 cases (3%), and sarcomatoid, 2 cases (3%). A high rate of nodal metastasis and poor survival were found for the basaloid and sarcomatoid neoplasms (5 of 7 patients with metastasis, 71%, and 5 of 8 dead of disease, 63%). Only 1 patient with a verruciform tumor (defined as a tumor of nonspecific papillary, warty, or verrucous type) had inguinal node metastasis and none died from penile cancer. An intermediate rate of metastasis and mortality (14 of 26, 54%, and 13 of 36, 36%, respectively) was found for typical SCC. Penile carcinomas are morphologically heterogeneous, and there is a correlation of histologic type and biologic behavior. This mandates accurate histologic subtyping by the pathologist.     

Histological classification of ovarian cancer

The histology of ovarian tumors exhibits a wide variety of histological features. The histological classification of ovarian tumors by the World Health Organization (WHO) is based on histogenetic principles, and this classification categorizes ovarian tumors with regard to their derivation from coelomic surface epithelial cells, germ cells, and mesenchyme (the stroma and the sex cord). Epithelial ovarian tumors, which are the majority of malignant ovarian tumors, are further grouped into histological types as follows: serous, mucinous, endometrioid, clear cell, transitional cell tumors (Brenner tumors), carcinosarcoma, mixed epithelial tumor, undifferentiated carcinoma, and others. Clear cell and endometrioid carcinomas are highly associated with endometriosis. In stage distribution, serous carcinoma is found predominantly is stage III or IV. In contrast, clear cell and endometrioid carcinomas tend to remain confined to the ovary. Clear cell and endometrioid carcinomas may be unique histological types compared with serous carcinomas with respect to stage distribution and association with endometriosis.     

Metastatic Small Cell Carcinoma to the Thyroid Gland: a Pathologic and Molecular Study Demonstrating the Origin in the Urinary Bladder

Small cell carcinomas may occur in the thyroid gland. Infrequently, they are primary tumors, and have been interpreted as variants of medullary thyroid carcinoma. However, the vast majority of small cell carcinomas involving the thyroid gland are metastatic tumors. In some cases, demonstration of the primary tumor is not easy. An example of a small cell carcinoma metastatic to the thyroid is presented in this report. The primary tumor was a small cell carcinoma that occurred as a minor component in a transitional carcinoma of the urinary bladder. The microscopical and immunohistochemical features of both tumors, in the thyroid and the bladder, were identical. Moreover, both tumors exhibited an identical mutation in p53, as well as similar loss of heterozygosity at 10q23 and RASSF1A promoter hypermethylation, clearly indicating that the bladder tumor was the site for the primary tumor of the patient.     

Endometrial carcinomas: a review emphasizing overlapping and distinctive morphological and immunohistochemical features

This review focuses on the most common diagnostic pitfalls and helpful morphologic and immunohistochemical markers in the differential diagnosis between the different subtypes of endometrial carcinomas, including: (1) endometrioid versus serous glandular carcinoma, (2) papillary endometrioid (not otherwise specified, villoglandular and nonvillous variants) versus serous carcinoma, (3) endometrioid carcinoma with spindle cells, hyalinization, and heterologous components versus malignant mixed müllerian tumor, (4) high-grade endometrioid versus serous carcinoma, (5) high-grade endometrioid carcinoma versus dedifferentiated or undifferentiated carcinoma, (6) endometrioid carcinoma with clear cells versus clear cell carcinoma, (7) clear cell versus serous carcinoma, (8) undifferentiated versus neuroendocrine carcinoma, (9) carcinoma of mixed cell types versus carcinoma with ambiguous features or variant morphology, (10) Lynch syndrome-related endometrial carcinomas, (11) high-grade or undifferentiated carcinoma versus nonepithelial uterine tumors. As carcinomas in the endometrium are not always primary, this review also discusses the differential diagnosis between endometrial carcinomas and other gynecological malignancies such as endocervical (glandular) and ovarian/peritoneal serous carcinoma, as well as with extra-gynecologic metastases (mainly breast and colon).     

Evaluation of histologic, morphometric, and immunohistochemical criteria in the differential diagnosis of small cell carcinomas of the cervix with particular reference to human papillomavirus types 16 and 18.

Clinicopathologic analyses including immunohistochemical, morphometric, virologic, and DNA ploidy studies were performed on seven cases of small cell (undifferentiated) carcinoma (SCC) and 13 cases of small cell squamous carcinoma (SCSC) of the uterine cervix in an attempt to evaluate which criteria are the most useful in identifying aggressive cervical carcinomas composed of small cells. Highly malignant behavior was found to correlate most closely with the histologic pattern of the tumor. Diffuse infiltration by round to spindle-shaped cells with hyperchromatic nuclei similar to small cell carcinoma in other organs correlated with a high frequency of lymph node metastasis and tumor recurrence. In contrast, tumors with well-defined nests similar to large cell nonkeratinizing squamous cell carcinoma were associated with low rates of lymph node metastasis and recurrence. Although there were trends in the distribution of neuroendocrine and cytokeratin immunohistochemical markers, frequency of detection of HPV 16 and 18 DNA sequences, and ploidy patterns, these features showed considerable overlap and none assisted in consistently separating these two types of neoplasms. Consideration of several features, however, could assist in the differential diagnosis. Women with SCC tended to be younger (mean age 36 yr) compared to women with SCSC (mean age 50 yr). A squamous intraepithelial lesion, i.e., cervical intraepithelial neoplasia, was present in association with 60% of SCSC but was not found in any case of SCC. Tumors positive for keratin and negative for neuroendocrine markers were invariably SCSC, whereas those negative for keratin and positive for neuroendocrine markers were always SCC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Limitations in the interpretation of biopsies in patients with penile squamous cell carcinoma

Surgeons often perform small or superficial penile biopsies that are difficult to classify definitely with regard to a benign or malignant nature, and if malignant, cannot always be accurately subclassified. Staging and therapeutic decisions rely on the identification, in these materials, of pathologic parameters related to prognosis. In this study, we evaluated the accuracy and completeness of pathologic information obtained from biopsies of 57 consecutive patients with squamous cell carcinoma (SSC) of the penis, and compared it with the information obtained from penectomies. Diagnostic accuracy was determined by recording discordances of critical factors in biopsies and penectomies. The evaluated parameters were as follows: cancer diagnosis, histologic type, tumor grade, depth of invasion (anatomical levels), and vascular invasion. Histologic subtypes of SCC were the following: usual 37, verruciform 11, mixed 7, pseudohyperplastic 1, and sarcomatoid 1. Grades were 1, 2, and 3 (well, moderately and poorly differentiated). Levels of invasion were lamina propria, corpus spongiosum, and corpus cavernosum in the glans; and lamina propria, dartos, and skin in the foreskin. In 2 patients with well-differentiated tumors a diagnosis of cancer could not be established in biopsy material. In 17 cases (30%) there was a biopsy-penectomy discordance of histologic types, especially of verruciform and mixed carcinomas. Biopsies failed to identify the correct histologic grade in 30% of the cases. A higher grade was usually identified in penectomy specimens. Because biopsies were superficial, the deepest point of invasion could not be determined in 91% of the cases. Vascular invasion was identified in biopsies in only 1 of 8 patients. In summary, biopsies were useful for cancer diagnosis except in 2 differentiated variants of penile squamous cell carcinoma. However, important pathologic parameters related to prognosis were missed on biopsy materials, and they were more accurately evaluated in penectomy specimens. We conclude that clinical and pathologic staging of penile cancer, at least in our material, cannot depend on biopsy information alone. Data from biopsies may be insufficient to make a decision whether to perform a groin dissection, or for prognostic evaluation in those patients in whom other treatment modalities (such as radiotherapy or chemotherapy) are being considered.     

Unusual forms of carcinoma of the urinary bladder.

Carcinomas of the urinary bladder, which differ histologically from the usual transitional cell carcinoma of the bladder, are reviewed. These tumors, which account for approximately 15% of all bladder carcinomas, have diverse microscopic appearances. They fall into four major categories: variant forms of urothelial (transitional cell) carcinoma, squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. In the first category, the most common are carcinomas with glandular or squamous differentiation. Less common, but more troublesome diagnostically, are variants in which the cells are spindle shaped (sarcomatoid carcinoma), form small cysts (microcystic carcinoma), or differentiate toward trophoblast. In other variants, the stroma has unusual features that may lead to diagnostic difficulty. These are carcinomas with pseudosarcomatous stroma, osseous or cartilaginous metaplasia, or osteoclast-type giant cells. Also reviewed are squamous cell carcinoma and its variant, verrucous carcinoma. Vesical adenocarcinoma has several variants, including signet-ring cell and clear cell types. Finally, the category of undifferentiated carcinoma, including small cell carcinoma, giant cell carcinoma, and lymphoepithelioma-like carcinoma, is discussed.     

CK7 expression in carcinomas of the Waldeyer's ring area

Primary carcinomas of the Waldeyer's ring area are typically nonkeratinizing squamous cell carcinomas (SCC). Their cervical lymph node metastases are not uncommonly cystic and filled with necrotic tumor cells. Some cysts, however, contain clear fluid. During the investigation of SCC producing "fluid-filled" cystic metastases, we evaluated hematoxylin and eosin (H&E) sections of 90 primary SCC for their site of origin. We analyzed the cytokeratin (CK) profile of primary and metastatic carcinoma with special focus on the expression of CK7, a putative marker for ductal differentiation. CK7 was expressed in submucosal minor salivary gland acini and ducts, but not in the squamous surface epithelium of the Waldeyer's ring. CK7 was expressed in 11 primary SCC (8 base of tongue/3 palatine tonsil). The CK7-positive SCC were deep-seated, arose from large excretory ducts of submucosal minor salivary glands, and showed only insignificant surface involvement. They were characterized by a solid infiltrative growth pattern of basaloid cells with focal ductal differentiation. Salivary ducts adjacent to the carcinoma showed extensive intraductal hyperplasia and metaplasia. All CK7-positive carcinomas produced CK7-positive cystic nodal metastases, most of which contained paucicellular fluid. No solid CK7-positive nodal metastases were identified. In summary, a subset of carcinomas occurring in the Waldeyer's ring area appear to arise from large excretory ducts of submucosal minor salivary glands with only limited surface involvement, express CK7, and produce CK7-positive cystic "fluid-filled" nodal metastases. The histomorphology and immunophenotype suggest that these carcinomas represent basaloid SCC arising from excretory ducts of the submucosal minor salivary glands.     

Ovarian carcinoma: current diagnostic principles

Ovarian cancer is the most common cause of death from a gynecologic cancer. The most common types of ovarian cancer are carcinomas of surface epithelial-stromal origin. Ovarian carcinomas are a heterogeneous group of neoplasms. Based on proposed different pathways of tumorigenesis, these tumors are divided into two broad subgroups (type I and II) with different biologic behaviour, prognosis and response to therapy. Type I tumors include low-grade serous adenocarcinoma, low-grade endometrioid adenocarcinoma, mucinous adenocarcinoma, malignant Brenner tumor and some clear cell carcinomas. These tumors are low-grade neoplasms evolving from a defined precursor lesion. Type II tumors are high-grade neoplasms including undifferentiated carcinoma, high-grade serous adenocarcinoma, high-grade endometrioid adenocarcinoma, malignant mixed Müllerian tumor and probably some clear cell carcinomas. At present, the histological type of ovarian carcinoma has only limited impact on the management of these tumors. However, with progress towards the type-specific treatment of ovarian carcinoma, accurate histopathological diagnosis of ovarian carcinoma becomes increasingly important. In this review we summarize recent advances in the histopathological diagnosis of ovarian carcinoma. Moreover, we mention genetic changes in different types of ovarian carcinoma.     

Follicular carcinoma

The workshop participants agreed on the following points regarding follicular carcinoma: Follicular carcinoma should be divided into two groups according to its degree of invasion: encapsulated and widely invasive. Patients in the first group only occasionally develop distant metastases, whereas in the second group the prognosis is much poorer. In encapsulated follicular tumors, high cellularity and nuclear atypia should not be used as criteria of malignancy; this diagnosis should be based on the presence of vascular or capsular invasion. Only tumor thrombi occurring in vessels in or outside the capsule should be regarded as indicative of vascular invasion. Capsular invasion should be diagnosed only if penetration of the whole capsule is seen. We agree that some tumor islands within the capsule may represent true tumor invasion, but we believe that some others may be due to capsular infoldings or tangential sectioning. Whenever tumor tissue within the capsule is seen, additional tissue blocks from the capsular area should be processed in a search for capsular penetration or vascular invasion. The degree of differentiation in follicular carcinoma does not correlate to the course of disease as clearly as the degree of invasion, although the so-called insular or poorly differentiated, subtype seems to have a poorer prognosis. Thyroid carcinomas composed of large eosinophilic cells (Hürthle cell carcinomas) usually show follicular differentiation and are therefore included in the category of follicular carcinoma. The same diagnostic criteria of malignancy that apply for other follicular tumors should be used when evaluating these tumors. Although follicular carcinomas often show foci of clear cells, tumors composed solely of clear cells are rare. Most pure clear-cell tumors in the thyroid represent metastatic tumors, usually from the kidney. In the distinction of follicular carcinoma from papillary carcinoma, all differential diagnostic criteria should be used. However, in some cases, the diagnosis can be based on one criterion only, mainly the presence of widespread ground-glass nuclei or abundant neoplastic papillae in papillary carcinoma. The presence of occasional papillae in encapsulated tumors composed of large eosinophilic cells is not sufficient for the diagnosis of papillary carcinoma if the other microscopic features of this tumor are lacking.     

Non-endometrioid carcinomas of the uterine corpus: a review of their pathology with emphasis on recent advances and problematic aspects

This review considers the clinical and pathologic features of the various histologic subtypes of endometrial carcinoma excluding those of pure endometrioid type, as the latter tumors were the subject of a previous contribution in the Journal (Vol. 9, No. 2). Non-endometrioid carcinomas, which account for about 10% of endometrial carcinomas, may pose a great array of problems in differential diagnosis, including their distinction not only from benign lesions but also endometrioid carcinoma and various tumors that may secondarily involve the uterine corpus. The most common subtypes are serous, mucinous, and undifferentiated. Rarer tumors are clear cell, squamous, transitional cell carcinomas, and a variety of poorly differentiated carcinomas with unusual forms of differentiation, such as hepatoid carcinoma, carcinomas with trophoblastic elements, and giant cell carcinoma. Mixed carcinomas, which are common, are also discussed, including those with a component of endometrioid carcinoma. The final section deals with endometrial involvement by metastatic tumors, lesions that, albeit rare, are sometimes neglected in the differential diagnosis of endometrial carcinomas. Important aspects emphasized are: (1) The potential for serous carcinoma to be mimicked by various forms of papillary endometrioid carcinoma. (2) The rarity of clear cell carcinoma and the greater frequency of clear cells in endometrioid carcinoma. (3) The frequency of mucinous epithelium in tumors of mixed cell type. (4) The frequency with which neoplastic mucinous epithelium originates from the endometrium. (5) The striking degree of differentiation of some squamous cell carcinomas. (6) The occasional predominance of non-endometrioid carcinomas (especially serous or undifferentiated carcinoma) within malignant mullerian mixed tumors. (7) The spectrum of reactive epithelial changes and other non-neoplastic abnormalities that may mimic serous or clear cell carcinoma.     

Divergent differentiation in endocrine and nonendocrine tumors of the skin

In the skin, endocrine tumors showing areas with nonendocrine features and nonendocrine tumors showing endocrine differentiation are present. (1) Neuroendocrine carcinomas with nonendocrine differentiation: Merkel cell carcinoma (MCC) of the skin has been frequently described in association with squamous cells carcinoma (SCC) which can arise separately (as synchronous or metachronous lesions) from MCC as well as closely intermixed. In the first event the possibility that the lesions are sustained by same causative factors (among which sun exposure is the most probable) is suggested. In cases of lesions closely intermixed the possibility of an origin from a common precursor is suggested. Furthermore, cases of MCC have been described to contain glandular, melanocytic, striated muscle, and lymphoepithelioma-like features. These latter findings further support the hypothesis of tumors showing divergent differentiations. (2) Nonendocrine tumors showing endocrine differentiation: Basal cell carcinoma (BCC) was the first cutaneous nonendocrine tumor described to contain neuroendocrine granules. Presence of endocrine features were subsequently confirmed with immunohistochemical studies. Endocrine features were then described in sweat gland apocrine and eccrine carcinomas. Endocrine elements present in BCC and in sweat gland carcinomas do not show morphological and immunohistochemical features of Merkel cells. Thus the possibility that these tumors develop an immature Merkel cell or a new type of endocrine cell of the skin is suggested. Tumors with follicular differentiation such as trichoblastomas and trichofolliculomas contain a high number of Merkel cells. As Merkel cells are numerous in hair follicles of human fetal skin, the possibility that these tumors recapitulate the human skin embryogenesis is suggested.     

Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.     

Clear cell renal cell carcinoma with smooth muscle stroma

A recent publication described 5 unusual clear cell renal tumors with prominent smooth muscle stroma that were characterized only by immunostaining. We report 3 additional tumors composed of clear cell renal cell carcinoma intimately admixed with abundant smooth muscle stroma. Epithelial differentiation of the malignant clear cell components and smooth muscle differentiation of the benign spindle cell stroma was confirmed by the immunostaining profiles and by electron microscopy. Fluorescence in situ hybridization analysis of chromosome 3 showed loss of the entire chromosome in 2 cases and loss of 3p in the third case. We therefore interpret these tumors as unique low-grade variants of clear cell renal cell carcinoma that have induced a prolific metaplastic stromal reaction. Extensive tissue sampling and immunostaining are recommended to distinguish cases with an extensive smooth muscle component from morphologically similar but benign lesions including angiomyolipoma, leiomyoma, or mixed epithelial and stromal tumor of the kidney.