International Journal of Surgical Pathology

The incidence of endometrial adenocarcinoma is high in North America and northern Europe, and low in Asia and Africa. This variance in frequency rates occurred in the late 1970s and its real cause has remained in question since. There is a widespread belief that endometrial adenocarcinomas associated with endometrial hyperplasia have a much better prognosis than those related to endometrial atrophy. This view is, in general terms, true but only because a high proportion of tumors arising from an atrophic endometrium are of serous/papillary, clear cell, or Grade 2-3 endometrioid carcinomas, in contrast to those developing from a hyperplastic endometrium, which are nearly all G1 endometrioid adenocarcinomas. These adenocarcinomas have, however, an excellent prognosis, no matter whether they are related to hyperplasia or atrophy, and taxonomically they form a single tumor group. In this regard, it is most reasonable to separate endometrial carcinomas into low-and high-grade tumors. The first are formed solely of G1 or “authentic” endometrioid adenocarcinomas, i.e., endometrioid neoplasms composed in their entirety of glandular elements without having traces of nonsquamous solid components. The high-grade tumors are formed of both endometrioid Grade 2-3 adenocarcinomas and nonendometrioid carcinomas—all of particularly aggressive behavior. The question of grading endometrioid adenocarcinomas in a precise and reproducible way becomes obvious. It is also believed that endometrial adenocarcinomas associated with endometrial hyperplasia are estrogen-primed, while those related to endometrial atrophy are deprived of hormonal stimulation. However, as we have shown in this laboratory recently, estrogen stimulation may be very common in endometrial neoplasms developing in an atrophic endometrium. For indeed most, if not all, postmenopausal atrophic endometria harboring adenocarcinomas contain actively proliferating glands, with high Ki-67 proliferation index, high epidermal growth factor receptor (EGFR) activity, high microvessel density (MVD), and rich in estrogen and progesterone receptors (ER and PR), indicative of a continuous low-level estrogenic stimulation. That there is a number of endometrial carcinomas that tend to develop in a milieu of antiestrogenic domination, following treatment for breast carcinoma, this may well represent a form of breast-endometrial hereditary disease and, certainly, merits further investigation.

Identification of new potential markers that may help in the diagnosis of benign and malignant thyroid lesions is needed. By comparative 2-dimensional gel electrophoresis of microdissected cells from tumors and normal thyroid tissue, we identified a new protein, S100C, which is highly expressed in papillary carcinomas. In order to validate this finding, we investigated the immunohistochemical expression and the potential role in diagnosis of these markers in 94 specimens representing the spectrum of malignant and benign thyroid lesions. Normal thyroid tissue was evaluated in 57 specimens. Galectin-3, a marker reported as specific for malignant lesions, was also evaluated in the same lesions. S100C protein was expressed in the nuclei of normal tissue, hyperplastic nodules, and follicular adenomas and carcinomas. Papillary carcinomas showed a strong, but cytoplasmic, pattern of staining. Galectin-3 immunostaining was strongly positive in papillary carcinomas, and negative in benign lesions, confirming its value in differential diagnosis. These findings suggest that immunohistochemical staining of S100C could be helpful in the pathological study of thyroid lesions, especially in cases in which follicular variants of papillary carcinoma and follicular carcinoma are considered in the differential diagnosis.

We estimated the prevalence and prognostic significance of neuroendocrine (NE) cells in a series of 208 resection specimens containing gastroesophageal junction (GEJ) adenocarcinomas, with 56 specimens containing Barrett’s mucosa. Immunohistochemically, chromogranin A (CGA) was positive in 49% (102/208) of GEJ adenocarcinomas and in 68% (38/56) of Barrett’s mucosas. CGA in GEJ tumors correlated with pTNM stage. CGA in Barrett correlated with pTNM stage and tumor grade of the adjacent carcinoma. Patients with CGA in Barrett had better survival than patients without CGA in Barrett, with 5-year survival percentages of 56% and 9%, respectively. In multivariate analysis, CGA in Barrett was an independent prognostic factor for survival after surgery. Therefore CGA in Barrett adjacent to GEJ adenocarcinoma might be helpful in the assessment of patient outcome.

To clarify the clinicopathologic and immunohistochemical features of dermatopathic lymphadenopathy not associated with mycosis fungoides among Japanese, 19 patients were studied. Seventy-four percent of the patients were more than 50 years old (median; 63 years, mean 61 years). Systemic symptoms such as fever were recorded in 68% and multicentric lymphadenopathy was noted in 83% of patients. An association of autoimmune disease or positivity of autoantibodies was recorded in 6 patients. Five patients showed cutaneous hypersensitivity reactions to a drug. Histologically, in addition to the dermatopathic lymphadenopathy, numerous immunoblasts were observed in 2 cases and sheet-like proliferation of mature plasma cells in 3 cases. Various atypical or malignant lymphoproliferative disorders exhibiting immunologic abnormalities such as angioimmunoblastic T-cell lymphoma or autoimmune disease-associated lymphadenopathy frequently occur in middle-aged and elderly patients. At least some of the patients with dermatopathic lymphadenopathy should be clinicopathologically differentiated from these lymphoproliferative disorders.

Vascular endothelial growth factor (VEGF) and C-KIT are involved in tumor progression in several human neoplasms. The aim of the present study has been to investigate their immunohistochemical expression in melanocytic lesions. We examined 11 compound nevi, 12 dysplastic nevi, and 18 melanomas. Immunostaining for VEGF was observed only in melanomas; c-kit expression was detected in melanomas (higher in radial than in vertical growth phase) and in nevi (predominantly in the junctional component). Our data indicate that assessment of VEGF expression might aid in the differential diagnosis between dysplastic nevi and melanomas. Moreover, VEGF might be a candidate for targeted therapy. The loss of c-kit expression might contribute to melanoma progression.

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.

Hamartomas were first described by Albrecht in 1904, who defined them as tumor-like malformations in which there was abnormal blending of the normal components of an organ. The myoid hamartoma is a rare benign lesion of the breast and has an uncertain origin, possibly in the walls of the blood vessels, muscularis mammillae of the areolae, and mainly in myoepithelium. We report 3 cases of myoid hamartomas of the breast, with the clinical, radiologic, and histopathological findings, and review the literature. The 3 lesions showed normal breast ducts and lobules, entrapped by a muscular stroma and some foci of mature adipose tissue. The muscular origin of part of the stroma was confirmed by strong reactiveness with smooth-muscle actin.

We describe an alveolar adenoma of the lung with 3 previously unreported findings, which expand both the clinical and the morphologic spectrum of this rare tumor: presentation as a cystic nodule, foci of mature adipocytes, and S-100 positivity of the mesenchymal cells. Furthermore, using a laser capture microdissection technique under microscope visualization, we analyzed multiple chromosomal loci in both the epithelial and mesenchymal components of the lesion, showing microsatellite alterations and loss of heterozygosity in the former but not in the latter.

Postradiation sarcomas are rare, and the most commonly reported ones are malignant fibrous histiocytoma, osteosarcoma, angiosarcoma, fibrosarcoma, malignant peripheral nerve sheath tumor, and high-grade pleomorphic sarcoma, not otherwise specified. There are a few case reports of postradiation rhabdomyosarcomas following treatment of retinoblastoma, breast cancer, endometrial adenocarcinoma, and Hodgkin’s disease. Secondary neoplasms following radiation and surgical treatment of rectal adenocarcinomas have not been reported in the English literature. We report a case of pleomorphic rhabdomyosarcoma of the anterior abdominal wall following treatment of rectal carcinoma, and we review the literature.

Prostatic adenocarcinomas commonly exhibit neuroendocrine differentiation as demonstrated by immunohistochemistry. However, true carcinoids of the prostate are rare. We describe herein a case of a primary carcinoid occurring synchronously with a conventional adenocarcinoma in the prostate of a 66-year-old man. The carcinoid measured 0.2 × 0.2 cm and did not show contiguity with adjacent conventional, moderately differentiated adenocarcinoma. Immunohistochemical stains for chromogranin and neuron-specific enolase were strongly immunoreactive in the carcinoid but not in the adenocarcinoma. Both neoplasms demonstrated positive staining for prostatic acid phosphatase and prostate-specific antigen. Owing to the relatively minute size of the carcinoid, the possibility that this tumor will impact negatively on the patient’s overall prognosis is not anticipated.

A 76-year-old man complained of lumbago, and a subsequent detailed examination revealed a mass in the left kidney. Macroscopically, multiple cysts were recognized in the bilateral kidney; the tumor proliferated predominantly in the renal medulla and showed a whitish color with focal necrosis and hemorrhage. A histologic examination of the surgically resected tumor showed various growth patterns, such as solid, tubular, and papillary, by tumor cells. The diagnosis of collecting duct carcinoma (CDC) was made. Furthermore, tumor cells contained globular inclusions resembling hyaline globules and large eosinophilic inclusions, resulting in rhabdoid features, in the cytoplasm. Histochemically, globular inclusions were positive for periodic acid-Schiff (PAS) with diastase pretreatment. Immunohistochemically, large esosinophilic inclusions were reactive for vimentin. Although these findings are rare in CDCs, they should be recognized in the pathologic spectrum of CDCs.

We report 3 cases of a new renal cell tumor entity with a review of the literature. These 3 cases were retrieved from the files of this institution from 1991 to 2002. The clinical data and all histologic slides were reviewed and an immunohistochemical study was performed. Patients were all females. Tumors were almost similar with well-defined margins. Tumor architecture was tubular and focally fusiform with an abundant myxoid stroma. Tumor cells were low cuboidal, slightly eosinophilic with low nuclear grade. Immunohistochemistry was in favor of a distal nephron differentiation. All patients were healthy after surgery. We describe 3 cases of a new clinicopathological entity entitled low-grade tubular myxoid renal tumor with a benign clinical course.