Typical and atypical carcinoid tumors of the lung: a clinicopathological correlation of 783 cases with emphasis on histological features.

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcomes. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2 mm2, necrosis, lymphatic invasion, and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlated with clinical outcomes. Based on our analysis, we consider that the separation of low- and intermediate-grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of overgrading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcomes.

Cutaneous Malignant Peripheral Nerve Sheath Tumor.

Cutaneous malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas of neuroectodermal origin arising in the dermis and/or subcutis. In contrast with their deep soft tissue and visceral counterparts, cutaneous MPNSTs are rarely associated with neurofibromatosis type 1. Two main subtypes of cutaneous MPNST can be distinguished histologically: conventional (ie, spindle cell) and epithelioid MPNST. The 2 subtypes also differ in predilection for deep versus superficial locations, association with preexistent benign peripheral nerve sheath tumors and S100 immunohistochemistry. Herein, we review current knowledge of cutaneous MPNST and discuss its differential diagnosis.

Cutaneous Osteoblastic Osteosarcoma: Report of 2 New Cases Integrated With SATB2 Immunohistochemistry and Review of the Literature.

We report 2 cases of primary dermal osteosarcoma. The patients were an 88-year-old man and a 72-year-old man complaining of masses occurring in the ear pavilion and the palm, deemed suspicious for basal cell carcinoma and metastatic colonic carcinoma, and were treated by resection. Microscopically, both featured a dermal lesion mostly composed of atypical spindle cells within a fibrous to hyaline matrix often showing mineralization. Osteoid material was rimmed by atypical tumor cells and was also associated with osteoclast-like giant cells. Tumor cells were positive for SATB2 and negative for markers of epithelial (low-molecular and high-molecular weight cytokeratins, epithelial membrane antigen, p63), melanocytic (S100 protein, HMB45, Melan A), and skeletal/smooth muscle differentiation (desmin, myogenin). No further therapy has been administered. Follow-up at 6 (case 1) and 8 months (case 2) was uneventful. A brief differential diagnosis discussing cutaneous tumors capable of showing osseous differentiation is summarized, along with a review of the pertinent literature. The specificity and sensitivity of SATB2 is also shortly addressed.

Lipophyllodes of the breast. A reappraisal of fat-rich tumors of the breast based on 22 cases integrated by immunohistochemical study, molecular pathology insights, and clinical follow-up.

We have studied 22 cases of mammary lipophyllodes tumors (LPT), analyzing their clinicopathologic features along with available follow-up. All cases were tested for cytokeratins, S100 protein, and MDM2, and in selected cases for estrogen receptor, smooth muscle actin, bcl2, desmin, and myogenin. Patients were women aged 21 to 69 years (average, 45 years), and LPT size ranged from 1.6 to 30 cm (average, 9.7 cm). Microscopically, LPT segregated as follows: atypical lipoma-like tumor/well-differentiated liposarcoma (ALT/WDL), 8 cases; myxoid, 6; and pleomorphic/poorly differentiated/round cell, 8, including a case of dedifferentiated liposarcoma. Immunohistochemistry studies showed focal positive staining for S100 and CD34 in most ALT/WDL, and desmin and myogenin in 2 cases with evidence of rhabdomyoblastic differentiation. MDM2 positivity was focally seen in 1 case. Follow-up was available in 8 cases. Multiple recurrent tumors were seen in 2 patients, and metastatic disease to the lung was seen in 2 patients. In 4 patients with a follow-up between 2 and 15 years there was no evidence of recurrent or metastatic disease. Patients with ALT/WDL (2/2) were alive with no evidence of disease; 2 of 4 patients with myxoid liposarcoma component experienced tumor recurrence, whereas pleomorphic liposarcoma LPT pursued a less favorable course although only 1 patient died of the condition. Absence of MDM2 reactivity in most cases seems not as meaningful as in fatty tumors of somatic soft parts.

Biphasic Squamoid Alveolar Renal Cell Carcinoma: A Distinctive Subtype of Papillary Renal Cell Carcinoma?

Biphasic squamoid alveolar renal cell carcinoma (BSARCC) has been recently described as a distinct neoplasm. Twenty-one cases from 12 institutions were analyzed using routine histology, immunohistochemistry, array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization. Tumors were removed from 11 male and 10 female patients, whose age ranged from 53 to 79 years. The size of tumors ranged from 1.5 to 16 cm. Follow-up information was available for 14 patients (range, 1 to 96 mo), and metastatic spread was found in 5 cases. All tumors comprised 2 cell populations arranged in organoid structures: small, low-grade neoplastic cells with scant cytoplasm usually lining the inside of alveolar structures, and larger squamoid cells with more prominent cytoplasm and larger vesicular nuclei arranged in compact nests. In 9/21 tumors there was a visible transition from such solid and alveolar areas into papillary components. Areas composed of large squamoid cells comprised 10% to 80% of total tumor volume. Emperipolesis was present in all (21/21) tumors. Immunohistochemically, all cases were positive for cytokeratin 7, EMA, vimentin, and cyclin D1. aCGH (confirmed by fluorescence in situ hybridization) in 5 analyzable cases revealed multiple numerical chromosomal changes including gains of chromosomes 7 and 17 in all cases. These changes were further disclosed in 6 additional cases, which were unsuitable for aCGH. We conclude that tumors show a morphologic spectrum ranging from RCC with papillary architecture and large squamoid cells to fully developed BSARCC. Emperipolesis in squamoid cells was a constant finding. All BSARCCs expressed CK7, EMA, vimentin, and cyclin D1. Antibody to cyclin D1 showed a unique and previously not recognized pattern of immunohistochemical staining. Multiple chromosomal aberrations were identified in all analyzable cases including gains of chromosomes 7 and 17, indicating that they are akin to papillary RCC. Some BSARCCs were clinically aggressive, but their prognosis could not be predicted from currently available data. Present microscopic, immunohistochemical, and molecular genetic data strongly support the view that BSARCC is a distinctive and peculiar morphologic variant of papillary RCC.

Desmoplastic melanoma: an updated immunohistochemical analysis of 40 cases with a proposal for an additional panel of stains for diagnosis.

Desmoplastic melanoma (DM) is histologically characterized by a proliferation of spindle melanocytes dispersed in a collagenous stroma that can be mistaken for a variety of neoplasms. The purpose of this study was to analyze 40 cases of DM with a comprehensive panel of immunohistochemical markers (KBA.62, p16, Ezrin, WT-1, MITF-1, SOX-10, CD117, SOX-2, nestin, PNL2, p75, MART-1, gp100 and S100p) to obtain a more complete understanding of the potential use of these antibodies in the diagnosis of DM. We found that all cases of DM expressed p16, WT-1, SOX-10, nestin and S100p and 95% of cases expressed p75. There was variable expression with Ezrin, SOX-2, KBA.62, MART-1 and HMB-45. Most DMs did not express MITF-1, PNL2 and CD117. Conditions that may enter in the histologic differential diagnosis of DM, including dermal scars, fibromatosis and dermatofibromas were also studied. Nearly all control cases also stained positive for p16 but were negative for WT1, SOX10, nestin, p75 and S-100p, as well as for most of the other markers tested. We conclude that a panel of S-100p, WT1, SOX10, p75 and nestin may constitute the optimal panel with the most sensitive and specific combination of immunostain available for the diagnosis of DM.

Selected cases from the Arkadi M. Rywlin international pathology slide series: granular cell nevus of congenital type: a melanocytic proliferation exhibiting distinct morphologic, immunohistochemical, and ultrastructural features.

A case of combined melanocytic nevus characterized by extensive granular cytoplasmic changes is described. Clinically, the lesion presented as an irregular, slightly asymmetric, and raised pigmented lesion of back with indistinct borders. Microscopically, a congenital pattern of distribution of melanocytes could be recognized growing along follicular and adnexal units. Melanocytes were arranged in sheets of epithelioid cells with abundant granular cytoplasm. A minor component featuring conventional dermal melanocytes was also present. Mitotic figures were not recognized. Immunohistochemistry was positive for Melan A and S100 protein in both conventional melanocytes and granular cells. In addition, the granular cells were also strongly positive for HMB45 and NKI-C3. The proliferative marker Ki67/MIB1 was nonreactive. Ultrastructural examination showed large cells with round to oval nuclei and numerous scattered cytoplasmic granules showing features consistent with lysosomes or autophagosomes. No premelanosomes, glycogen, lipid, or other distinctive organelles could be identified. Clinical follow-up at 2 years was uneventful. This unusual lesion may represent a peculiar dermal melanocytic proliferation in which the abundant granular cytoplasm is most likely due to degeneration of melanosomes induced by autophagocytic activity. The striking cytoplasmic granularity observed in this lesion may lead to confusion with other conditions, thus warranting adding granular cell nevus to the phenotypic spectrum of benign melanocytic proliferations.

Liposarcomas of the posterior mediastinum: clinicopathologic study of 18 cases.

Sarcomas of the posterior mediastinum are rare and correspond mostly to neurogenic tumors. We studied 18 cases of liposarcoma presenting in the posterior mediastinum; because of their unusual location, some of these tumors posed difficulties for diagnosis. There were 11 men and 7 women aged 29-87 years (mean: 57). The tumors were large lobulated masses ranging from 6 to 30 cm in greatest diameter (median: 15 cm). Symptoms included cough, dysphagia, and chest pain. Four patients were asymptomatic and the tumors were discovered incidentally on chest X-rays. Histologically, 10/18 (55%) cases were atypical lipomatous tumor/well-differentiated liposarcoma, one of which harbored a smooth muscle component (lipoleiomyosarcoma); 3/18 (16%) were de-differentiated liposarcoma, one of which also harbored a smooth muscle component; 3/18 (16%) were myxoid/round cell liposarcoma; and 2/18 (11%) were pleomorphic liposarcoma. The cases of well-differentiated liposarcoma were mostly of the sclerosing type; however, five of them also showed prominent myxoid stroma closely resembling myxoid liposarcoma. Immunohistochemistry was performed in selected cases; 4/8 cases tested showed focal positivity for S-100 protein and 5/8 cases showed nuclear positivity for MDM-2. The three cases of myxoid liposarcoma were all negative for MDM2. Both cases of lipoleiomyosarcoma showed positivity for SMA and desmin in the smooth muscle component. FISH was performed in two cases of well-differentiated liposarcoma and high levels of amplification of MDM2 at 12q13-15 were observed; the CHOP translocation at 12q13.1-q13.2 was absent in both cases. Complete surgical excision was performed in 11 cases; however, negative surgical margins were achieved only in four. Clinical follow-up ranging from 1 to 192 months (median 28 months) was available for 13 patients. Two patients with myxoid/round cell liposarcoma died of tumor after 4 months and 3 years, respectively. Both had widely disseminated metastatic disease at the time of death. Six patients (6/10) with well-differentiated liposarcoma were alive and well with no evidence of disease (at 4, 7, 12, 15, and 25 months) and three (3/10) were alive with disease (at 3, 4, and 6 months). One patient with well-differentiated liposarcoma had multiple recurrences and a liver metastasis after 14 years; however, the patient was alive and well at 16 years. Five patients were lost to follow-up. In general, the biologic behavior of liposarcomas in the posterior mediastinum seems to correlate well with the histologic subtype and mirrors that of their counterpart in the retroperitoneum.

Glioma-associated stem cells: a novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas.

BACKGROUND: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. METHODS AND FINDINGS: We isolated glioma-associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival and malignant progression free-survival. CONCLUSIONS: The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma-initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma.

Signet ring cell angiosarcoma: a hitherto unreported pitfall in the diagnosis of epithelioid cutaneous malignancies.

We report 2 cases of cutaneous epithelioid angiosarcoma featuring predominantly signet ring cells. The patients-a woman, 68 years of age, and a man, 85 years of age, respectively-were referred for slowly growing indurated plaques on their parietal and retroauricular skin. Microscopic examination showed diffuse dermal proliferations comprising polygonal cells and relatively abundant cytoplasm. Because the tumor cells often were distended by variably sized vacuoles pushing the nuclei to the periphery, the nuclear profile tended toward a crescent-like morphology. Abortive luminal formations were recognized. The tumor cells were positive for CD31, CD34, and D2-40/podoplanin, with no expression of epithelial or melanocytic markers. In 1 case, upon ultrastructural examination of paraffin-embedded tissue-cut from wax tissue and reprocessed-the optically empty spaces were surrounded by a membrane with ultrastructural features identical to those of the outer cell membrane, suggesting that these spaces corresponded to the formation of primitive intracytoplasmic lumina within the tumor cells. A few Weibel-Palade bodies also were noted. Our report offers further evidence that epithelioid angiosarcoma of the skin has a broad microscopic spectrum and that tumors displaying a preponderant population of signet ring cells pose further diagnostic challenges. A brief overview of cutaneous malignant tumors in the differential diagnosis of signet ring cell angiosarcoma is provided.

Hemangioblastoma-like clear cell stromal tumor of the lung.

The authors report 2 cases of an apparently unpublished stromal tumor of the lung characterized by a predominantly endobronchial growth pattern and benign-appearing clear cells. Both tumors were discovered incidentally in adult patients during routine workups for other medical reasons and treated with lobectomy. On gross inspection there was no evidence of infiltration of the adjacent lung tissue. Microscopically, both lesions featured monotonous oval-shaped to spindle-shaped cells growing in a vaguely nested pattern. The cytoplasm was slightly vacuolated or granular. In 1 case there was a variable admixture with mature fat. Immunohistochemistry was negative for markers of epithelial and stromal differentiation except for vimentin. A focal reaction for CD34 was seen in 1 case. No mutation of coding sequence of VHL gene was seen in one case. Medical follow-up at 1 year was negative for tumor recurrence or metastases. The broad differential diagnosis within the spectrum of stromal lung tumor is discussed. Owing to distinctive microscopic features such as the nesting of clear cells within a vascularized background, both tumors appeared similar to hemangioblastoma, although the expected immunohistochemical profile of the latter was not fully expressed. Because of pattern of growth seen in both lesions we believe that the appellation of endobronchial, hemangioblastoma-like clear cell stromal tumor may be provisionally designed.

Metastatic melanoma presenting as an isolated breast tumor: a study of 20 cases with emphasis on several primary mimickers.

CONTEXT: The mammary gland can be a site of metastasis in patients with malignant melanoma, which is easily recognized microscopically if clinical information is available. Nonetheless, metastatic melanoma presenting as an isolated mammary tumor can be more challenging to diagnose because it can simulate a primary breast carcinoma clinically and morphologically. OBJECTIVE: To review metastatic melanoma to the breast, presenting as primary breast carcinomas clinically and morphologically. DESIGN: The authors report 20 cases of metastatic melanoma clinically presenting as breast tumors. Cases with widespread metastatic presentation were excluded. RESULTS: Epithelioid and spindle cell tumors predominated, suggesting mammary ductal, papillary, or sarcomatoid carcinoma. Most cases (16 of 20) were submitted for consultation or second opinion owing to their unusual presentation in the breast, or to perform predictive/prognostic immunohistochemical assays. Seven cases had a remarkable phenotypic spectrum expanding the differential diagnosis to large cell lymphoma, leiomyosarcoma, medullary carcinoma, malignant schwannoma, and liposarcoma. Tumor cells were negative for cytokeratin stains and positive for S100 protein, HMB-45, and Melan-A. Negative staining was also observed for epithelial membrane antigen, CD45, desmin, estrogen and progesterone receptors, and human epidermal growth factor receptor 2. CONCLUSIONS: Metastatic melanoma may simulate a broad spectrum of primary breast malignancies. Although the application of a simple panel of antibodies assists in rendering the correct interpretation, lesions presenting as isolated breast tumors may introduce a significant diagnostic difficulty, especially when there is inadequate patient history and/or limited biopsy material. Further challenges are introduced by the extraordinary phenotypic plasticity of metastatic melanoma. Awareness of this pattern variance is essential to avoid inappropriate treatment, especially in cases simulating a "triple negative," poorly differentiated carcinoma of the breast.

Intrapulmonary solitary fibrous tumors: clinicopathologic and immunohistochemical study of 24 cases.

Solitary fibrous tumor (SFT) is a ubiquitous neoplasm that arises most commonly from the pleura. SFT arising within lung parenchyma (intrapulmonary SFT) has been rarely reported and is therefore not well recognized. We present a clinicopathologic and immunohistochemical study of 24 cases of primary intrapulmonary SFT. Patients' ages ranged from 44 to 83 years (mean, 58 y). None of the patients had evidence or history of a similar tumor elsewhere. Tumor size ranged from 2.3 to 22 cm (mean, 8.5 cm). On the basis of the degree of cytologic atypia, cellularity, mitotic activity, and areas of necrosis, the lesions were divided into low-grade, intermediate-grade, and high-grade histology. Twenty-one tumors showed the conventional features of SFT of low-grade histology (<5 mitoses per 10 high-power fields), with alternating bands of rope-like collagen flanked by a bland-appearing spindle cell proliferation. Hemangiopericytic, angiofibromatous, and a neural-like plexiform growth pattern were also observed. Five of 21 cases showed an "adenofibromatous" appearance imparted by entrapped normal airspaces at the advancing edges of the lesion. One intermediate-grade tumor showed overall increased cellularity with plump, pleomorphic nuclei, 5 to 10 mitoses per 10 high-power fields, and focal areas of classic SFT. Two cases showed high-grade features at initial presentation, with areas resembling a pleomorphic high-grade sarcoma admixed with foci of conventional, low-grade SFT. Immunohistochemical staining analyses performed in 13 cases showed positivity of the tumor cells for CD34, bcl-2, and CD99 in the majority of cases tested. Clinical follow-up was available in 18 patients, with long-term follow-up (>5 y) in 6. Fourteen (14/18) patients were alive and well without evidence of disease 1 month to 14 years after initial diagnosis. Three patients died of their tumors after 4, 5, and 7 years; in 2 of them the initial tumor was of low-grade histology, but the recurrence/metastases showed a high-grade histology; the third fatal case showed a tumor with high-grade histology at initial diagnosis. One patient with intermediate-grade histology also had chest wall metastases at 5 years but was subsequently lost to follow-up. The results of our study indicate that although tumors with overtly malignant histologic features can be expected to behave as high-grade sarcomas, tumors with bland-appearing morphologic features at presentation may also follow an aggressive behavior. Adequate excision with close clinical follow-up, thus, appears to be the most prudent course of action for the management of primary intrapulmonary fibrous tumors.

Cutaneous clear cell sarcoma: report of three cases of a potentially underestimated mimicker of spindle cell melanoma.

Clear cell sarcoma is a unique soft tissue tumor with distinct microscopic features that include a nested or fascicular pattern of spindle cells accompanied by larger wreath-like giant cells scattered throughout. It harbors a unique EWSR1-ATF1 gene fusion secondary to a t(12;22)(q13;q12) translocation. Recently, it was reported that clear cell sarcoma can occur in the skin and mimic a broad spectrum of entities, including spindle cell melanoma. Here, we describe 3 new cases of clear cell sarcoma of the skin, all of which were confirmed molecularly. The patients, a 12-year-old boy, a 29-year-old woman, and a 60-year-old man, had cutaneous lesions on the thigh, dorsum of foot, and sole, respectively. All 3 lesions were originally considered suspicious of spindle cell melanoma. Microscopically, the lesions featured nodular proliferation centered in the dermis that consisted of discrete fascicles of spindle cell enmeshed by thin fibrous strands. Wreath-like cells were present in all cases. Tumor cells were positive for S100 protein (3 of 3 cases), melan A (2 of 3 cases), HMB 45 (1 of 3 cases) although a junctional melanocytic proliferation was seen in 1 case. Sentinel lymph node biopsy was negative in 2 patients. Follow-up was uneventful in 2 patients, whereas the other patient developed a lymph node metastasis 5 months after primary tumor excision. This study confirms that malignant dermal tumors that mimic but do not exactly replicate spindle cell melanoma should raise suspicion for cutaneous clear cell sarcoma and prompt the investigation for the confirmatory gene fusion t(12;22).

Cutaneous pseudolymphoma following tattoo application: report of two new cases of a potential lymphoma mimicker.

The authors report 2 cases of cutaneous pseudolymphoma that occurred in 2 young adult patients who referred for relentlessly growing nodules that appeared within 4 to 5 months after the application of a mercury-based tattoo. Systemic symptoms were not present and there was no evidence of lymph node enlargement. Clinically, both lesions were limited to the red, mercury-based areas of the tattoo. Microscopic examination featured a dense cellular infiltrate composed of polytypic T cells in the upper to mid-dermis, coupled with focal interface tissue reaction. Scattered macrophages contained finely granular particles in their cytoplasm. In addition, extracellular pigment particles were also recognized. Collections of epithelioid macrophages were present in both cases and were reminiscent of epithelioid granulomas. This study confirms evidence that, among skin diseases featuring a dense lymphoid infiltrate, cutaneous pseudolymphoma secondary to tattooing is a rare but not exceptional source of diagnostic challenges.

B-cell lymphoma presenting as acute pancreatitis.

BACKGROUND: Pancreatic lymphoma is uncommon, representing less than 0.5% of pancreatic tumors, with diffuse large B-cell lymphoma being the predominant histotype. Acute pancreatitis associated with pancreatic lymphoma is rare. CASE REPORT: We describe a case of synchronous pancreatic and pulmonary localizations of non-Hodgkin's lymphoma in a 42-year-old man who presented with acute pancreatitis. Acute pancreatitis resolved after standard treatment with a fasting regimen, gabexate mesilate and parenteral nutrition. However, ultrasound scan and abdominal computed tomography revealed two hypoechogenic areas within the pancreas, and chest X-ray film showed a pulmonary infiltrate in the right basal field. A percutaneous fine-needle aspiration biopsy of the pulmonary infiltrate under computed tomography guidance demonstrated a diffuse infiltration by atypical lymphoid cells positive for leukocyte common antigen, CD20 and CD30. Percutaneous fine-needle aspiration biopsy under ultrasound guidance of the pancreatic mass confirmed the diagnosis of diffuse large B-cell lymphoma. The patient was classified as stage IV-A, low-intermediate risk and received 6 cycles of chemotherapy. CONCLUSION: This is the first case of large B-cell lymphoma presenting with concomitant primary pancreatic and pulmonary involvement. Pancreatic lymphoma is uncommon and represents a rare cause of acute pancreatitis. The discovery of a pancreatic mass needs pathologic diagnosis to distinguish lymphoma from carcinoma or autoimmune pancreatitis. and IAP.

Residual prostatic tumour in the surgical bed following radical prostatectomy in organ-confined prostate cancer: possible prognostic significance.

INTRODUCTION AND OBJECTIVES: The aim of our study was to verify the impact of benign and malignant residual glandular tissue on surgical bed after radical prostatectomy, in terms of both biochemical and clinical disease progression, in a group of patients with pathologically organ-confined cancer of the prostate (PCa). MATERIAL AND METHODS: Files from 70 consecutive patients who undergone radical retropubic prostatectomy (RRP) for organ-confined PCa were retrospectively evaluated. During each intervention, after prostate removal, biopsies of the surgical bed were obtained from the following sites: urethral/periapical section margin, basal, left and right postero-lateral and under/retrotrigonal regions. No patient was been previously treated with either radiation or hormone therapy. We evaluated the relationship between the presence of either benign or malignant prostatic cells at surgical bed biopsies and the following parameters: postoperative serum PSA levels, definitive Gleason score, tumour staging, margin status. RESULTS: In all cases pathological stage was pT2NOMO, an immediate postoperative PSA zeroing occurred and surgical margins were negative. Surgical bed biopsies after prostate removal were positive for malignant cells in 5/70 cases (7.1%) and for benign prostatic cells in 16/70 patients (22.9%). Overall a biochemical disease progression was observed in 13/70 cases (18.6%): 1 case with surgical bed biopsies positive for cancer; 3 cases with biopsies positive for benign prostatic tissue; 9 patients with biopsies negative for prostatic tissue residuals. In this latter group 2 cases of disease progression were observed. Stratifying patients according to biopsy features, we did not find any significant difference between groups concerning preoperative PSA (p = 0.319), prostate weight (p = 0.158), pathological staging (p = 0.371), Gleason score (p = 0.457), follow-up (p = 0.144), biochemical progression rates (p = 0.553). At logistic regression model the only statistically significant association was between disease progression and preoperative PSA (p = 0.026). Stratifying patients with no malignant biopsies in two subgroups (presence and absence of residual benign prostate tissue) no statistically significant differences were detected in terms of disease relapse (p = 0.158). CONCLUSIONS: In patients with pathologically organ-confined PCa, minimal neoplastic tissue residuals might not significantly affect medium-long-term prognosis: 80% of patients with positive biopsy showed undetectable serum PSA levels after a median follow-up over 5 years. In contrast, surgical margins positive for benign prostatic glands was not significantly related to a possible disease relapse/progression.

Epithelioid melanoma of the rectum: reappraisal of a deceptive microscopic simulator.

We report 2 cases of rectal melanoma. The patients were a 48-year-old man and an 88-year-old woman. In both cases, the tumor presented as polypoid and necrotic masses, making initial diagnostic assessment difficult because of the regressive tissue changes. Microscopically, tumors were mostly composed of epithelioid, highly atypical cells mimicking poorly differentiated carcinoma or large cell lymphoma. Tumor cells were negative for keratin, leukocyte common antigen, and epithelial membrane antigen and positive for S100 protein and several melanoma markers, although in endoscopic biopsy specimens, the positive reaction was focal due to the limited viable tissue. One patient was treated with abdominoperineal resection. Pathologic examination of the surgical specimen revealed a polypoid mass infiltrating the muscle coat of the rectum. Local lymph nodes contained metastatic deposits. Microscopic examination of the rectal mucosa adjacent to the infiltrating neoplasm revealed colonization of the intestinal crypts by atypical melanocytes. This patient is alive 1 year after surgery with no evidence of recurrent disease. The other case was not deemed amenable to radical surgery because of the patient's advanced age and evidence of diffuse metastatic disease. She was alive 6 months after the initial diagnosis but was lost to follow-up. Data indicate that the diagnosis of melanoma, although feasible in large resection specimens, may be problematic in endoscopic biopsy, especially when only small tissue fragments are available and tumor regression hampers the accuracy of immunohistochemical stains. Documentation of intracryptic atypical melanocytes in nonneoplastic mucosa conceptually corroborates claims that rectal melanoma is related to preinvasive precursors as in cutaneous melanoma.

Epithelioid angiosarcoma of the skin: a study of 18 cases with emphasis on its clinicopathologic spectrum and unusual morphologic features.

We report 18 cases of cutaneous angiosarcoma with predominant or exclusive epithelioid morphology. Both sexes were similarly affected. Patients' ages ranged from 2 to 97 years, median 77.5 years; 2 were pediatric patients. In elderly patients scalp or facial lesions and cutaneous lesions arising within irradiated breast skin predominated. Limb lesions were seen in younger patients. Microscopically, the tumors were composed of packed polygonal cells with focal evidence of endothelial differentiation. Diverging phenotypes included syncytial growth of large cells with clear nuclei and prominent nucleoli, micronodules of tumor cells scattered in dermis, predominance of discohesive plasmacytoid polygonal cells with abundant bright eosinophilic cytoplasm, sheets of clear cells with coarse granular cytoplasm, trabecular and cord arrangement of tumor cells splaying the dermal collagen, or a pseudoglandular appearance owing to clear cell tubular arrangement with open lumina. These cases posed further diagnostic challenges simulating lymphoma, melanoma, lymphoepithelioma-like carcinoma, adnexal carcinoma, and neuroendocrine carcinoma. Immunohistochemical studies showed positivity for CD31 and CD34; no immunoreactivity was documented for other tested antigens including cytokeratins, S100 protein, melanocytic antigens, leukocyte common antigen, and desmin. Therapeutic modalities included combined local excision, chemotherapy, and radiotherapy, depending on patient clinical status. Of the 9 patients available for follow-up, 5 were alive and apparently well, 2 had recurrent disease, and 2 had died of tumor. Our data show that epithelioid cutaneous angiosarcoma may have a broad morphological spectrum, raising interpretive challenges on microscopy. In addition, its clinical presentation seems to differ in nonelderly patients, with lesions likely related to lymphedema or vascular malformations.