"Pure" primary large cell neuroendocrine carcinoma of the urinary bladder: case report, literature review and diagnostic criteria.

INTRODUCTION: Large cell neuroendocrine carcinoma (LCNC) is defined in the urinary bladder, as in other sites, as a high-grade neoplasm exhibiting neuroendocrine features at the H&E level, high mitotic activity and evidence of neuroendocrine differentiation by immunohistochemistry. We report a case of pure bladder LCNC with review of the literature. METHODS: A 68-year-old male presented with gross haematuria of two weeks' duration in October 2011. Transurethral resection and subsequently radical cystoprostatectomy (CP) with bilateral lymphadenectomy (L) were performed in December 2012. RESULTS: Urinary cytology identified malignant cells. Histologically, the tumour showed organoid nesting, trabecular growth, rosettes and perilobular palisading patterns, suggesting neuroendocrine differentiation. Immunohistochemical staining showed intense positivity for CD56. DISCUSSION: We examined all published pure bladder LCNC (12 cases) excluding mixed neoplasms. Small cell carcinoma of the urinary bladder pure LCNC of the bladder is a very aggressive malignancy, unresponsive to therapy, presents in an advanced stage and has a propensity for early metastasis. Prior to the advent of immunohistochemistry, such cases would most likely have been categorised as poorly differentiated, high-grade urothelial carcinomas.

Theory and practical application of superficial atypical melanocytic proliferations of uncertain significance (SAMPUS) and melanocytic tumours of uncertain malignant potential (MELTUMP) terminology: experience with second opinion consultation.

INTRODUCTION: The term superficial atypical melanocytic proliferations of uncertain significance (SAMPUS) is used to resolve discordance in diagnosis of "thin" melanocytic lesions. Melanocytic tumours of uncertain malignant potential (MELTUMP) is the descriptive term for an ill-defined group of dermal melanocytic tumours that exhibit features indicative of possible malignancy. We report our experience of collaboration with two leading international consultant pathologists in the diagnosis of melanoma in order to facilitate the practical application of the term SAMPUS and MELTUMP. METHODS: Twenty-seven cases of melanocytic lesions with interpretative problems were sent for consultation to Expert #1 (15 cases) and Expert #2 (12 cases). RESULTS: Two cases of MELTUMP and two cases of SAMPUS were diagnosed by Expert #1; three cases of MELTUMP and two cases of SAMPUS were diagnosed by Expert #2. Diagnosis was performed with H&E and molecular studies were not performed. DISCUSSION: Both experts included MELTUMP or SAMPUS atypical, ambiguous melanocytic lesions and melanomas. The diagnosis of SAMPUS and MELTUMP by consultant pathologists reflects the difficulty of classification with accuracy lesions that showed histological features of various atypical tumours or malignant melanoma. In these cases, biological potential may be established with molecular studies.

Ovarian fibromatous tumours of uncertain biological potential: study of three cases.

BACKGROUND: The classification of ovarian fibromatous tumours with high mitotic activity is controversial. CASES REPORT: The first case was an 18 x 17 x 10 cm left ovarian fibromatous tumour with 17 mitoses/10 HPF detected in a 44-year-old woman. The second case consisted of a 4 x 2.5 x 2 and a 2.5 x 2.5 x 2 cm fibrmatous tumours found, respectively, in the left and right ovaries of a 67-year-old woman. The mitotic count varied from 4 to 6/10 HPF. CONCLUSIONS: Prat & Scully reported that mitotic activity was the most important factor in diagnosing fibrosarcomas, and that cellular pleomorphism was not reliable. Irving et al. suggested that cellular fibromatous neoplasms with bland nuclear features and mitotic count of > or = 4 MFs/10 HPFs should be considered mitotically-active cellular fibromas rather than fibrosarcomas. We propose the term 'fibromatous tumours of uncertain biological potential' when an average mitotic count of 4 or more per 10 HPFs are found and nuclear atypia and necrosis are absent.

Sebaceous carcinoma of the vulva: critical approach to grading and review of the literature.

BACKGROUND: Sebaceous glands are abundant on the vulva, but vulvar sebaceous carcinoma (SC) is an uncommon neoplasm. METHODS: We report a case of SC of the vulva in a 51 year-old woman. RESULTS: The patient presented a 6-month history of an asymptomatic 2.5 x 1.5 cm exophytic tumour localized on the left labium majora. Tumorectomy was performed. Histologically, the lesion had an irregular lobular growth pattern composed of lobules or sheets of malignant cells separated by fibrovascular stroma. There was a mixture of sebaceous-type differentiation, small ducts and areas showing basaloid or squamous features. Centrally-located tumour cells showed moderate EMA immunoreactivity, especially enhancing cytoplasmic "bubbliness". Tumour cells were immunoreactive for CAM 5.2. The immunoreactivity for intranuclear p53 staining was > 10%. Southern blot hybridization and PCR studies did not detect HPV DNA. Hemivulvectomy was performed. After 18 months of follow-up, the patient has no evidence of recurrence, metastases or other malignant tumours. CONCLUSIONS: The grading of cutaneous SC proposed by Rutten et al. (World Health Organization Classification of Skin Tumours) and Patterson & Wick (Nonmelanocytic Tumours of the Skin. Armed Forces Institute of Pathology) is based on patterns of tumour growth rather than cytological features. Such grading of skin SC, including vulvar SC, should not be used since its prognostic value has not been sufficiently documented. As the number of reported vulvar SCs is very limited, their natural history is unknown and the optimal treatment has not been established. The follow-up of 7 reported cases supports the general opinion that the tumour may be aggressive. SC groin node metastases carry a devastating prognosis, and unrecognized disease in the inguinofemoral lymph nodes is nearly always fatal. The use of sentinel lymph nodes (SLN) has evolved as an effective surgical technique for identifying early subclinical regional nodal involvement for many solid tumours throughout the body for staging disease; this is because extra-ocular SCs cause widespread metastatic disease. In our opinion, SLN should be used in conjunction with wide local excision of the primary tumour to investigate regional subclinical metastases. In the presence of a positive sentinel node, early lymphadenectomy with or without radiotherapy could be used to reduce tumour-related morbidity and mortality. The histopathologic differential diagnosis of SC is wide-ranging, including virtually all other malignant clear cell tumours of the skin. The proliferative pattern, immunostaining and cytologic features permit exclusion of neoplasms that mimic SC, but a diagnosis of SC should be rendered only if the overall attributes of the lesion are appropriate for such a interpretation.

Oncocytic carcinoma of the parotid gland: case report and review of the literature.

OBJECTIVES: To date 70 cases of oncocytic carcinomas (OCs) have been described in 55 reports. We describe an OC of the parotid gland in a 56-year-old man with simultaneous breast cancer. METHODS: In June 2006, a 56-year-old man was referred to the Otorhinolaryngology Division for a painless right preauricolar mass. The facial nerve was functionally normal. Total parotidectomy with facial nerve preservation was performed. In January 2007, the patient was referred to the Surgical Division for a left mammary nodule. Total mastectomy with axillary lymphoadenectomy was performed. RESULTS: The mass of the parotid gland measured 3.5 x 3 cm. Histology showed sheets, islands and nests composed of large, round to polyhedral cells with fine, granular, eosinophilic cytoplasm and round vesicular nuclei, with prominent nucleoli. The tumour cells were positive for immunohistochemical staining with antimitochondria antibodies. Histological examination of the mammary tumour showed invasive ductal carcinoma Grade III (Nottingham Histologic Score) with metastasis in 12 axillary lymph nodes. Chemotherapy was performed. At present, the patient is free of recurrences or metastases. CONCLUSIONS: Histologically, there is a spectrum of malignant parotid gland neoplasms that have prominent eosinophilic granular cytoplasm due to increased number of mitochondria. OCs have cytoplasm packed with mitochondria, while the term "oncocytoid" should be employed for tumours that have abundant eosinophilic granular cytoplasm, but ultrastructurally do not possess marked mitochondrial hyperplasia. All reported cases of OC should be defined "oncocytic-like carcinoma" when only haematoxylin and eosin staining is performed.

Immunohistochemical expression and localization of somatostatin receptor subtypes in prostate cancer with neuroendocrine differentiation.

The aim of the study is to examine the tissue expression and localization of the somatostatin receptors (SSTRs) in prostate cancer (PCa) with neuroendocrine (NE) differentiation. The five SSTR subtypes (SSTR1 to 5) were evaluated immunohistochemically in the secretory cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 radical prostatectomies (RPs) with Gleason score 3+3=6 acinar PCa; 20 RPs with GS 4+4=8 and 4+5=9 PCa; and 20 RPs with PCa with NE differentiation. The basal cells were evaluated in Nep and HGPIN. In all groups the stromal smooth muscle and endothelial cells were also analyzed. Concerning the secretory cells, (i) the greatest mean proportions of cells with strong cytoplasmic staining in PCa were seen for SSTR2, mainly in the group of RP with NE differentiation, and for SSTR4 in all three groups; the mean values in HGPIN were intermediate between Nep and PCa; (ii) Membrane staining was seen for SSTR3 and SSTR4; the mean percentages of positive cells, higher in SSTR3 than in SSTR4, decreased from Nep to HGPIN and PCa in all three RP groups; in the latter two, the mean percentages were similar; and (iii) Nuclear staining was seen with SSTR4 and SSTR5; for SSTR4, the mean percentages in the PCa of the three groups were higher than in HGPIN and Nep, the highest proportion being with PCa with NE differentiation. Concerning the basal cells, in Nep the mean proportions of cells with strong staining intensity were greater for SSTR1 and SSTR3 than for the other subtypes, the lowest being with SSTR2; in HGPIN the highest mean propositions of positive cells was with SSTR3, the proportions in the three RP groups being similar. Concerning the stromal smooth muscle and endothelial cells, the highest mean values being in SSTR1 and the lowest in SSTR5; for the former subtype the highest proportion of endothelial cells with strong intensity was seen in the RP NE group. In conclusion, this immunohistochemical study expands our knowledge on the expression and localization of five SSTRs in the various tissue components in the prostate with PCa with NE differentiation, compared with conventional PCa. Typing somatostatin receptor expression in NE tumours could be of relevance to target somatostatin analogue-based diagnostic approach and treatment.

Extracutaneous seborrheic inclusion cyst: an unusual presentation.

Seborrheic inclusion cyst is an unusual variant of epidermal cyst characterized by parietal histology similar to seborrheic keratosis. Cysts with such changes have been called "seborrheic keratosis-like changes in epidermal cyst" or "epidermoid cyst with seborrheic verruca-like cyst wall" or simply "seborrheic cyst". To date, this lesion has been described exclusively in cutaneous sites. We describe the first case of an extracutaneous seborrheic inclusion cyst arising from round ligament. A 30-year-old female was referred to our institution for abdominal pain. Ultrasonography showed a hypoechoic heterogeneous, round mass adjacent to the lower extremity of the left ovary, measuring 4.5 cm in maximum diameter. Contrast-enhanced computed tomography of the pelvis in the venous phase showed a round (4.5 cm in diameter) cystic lesion with inhomogeneous fluid content in the side of the left large ligament and anterior to the homolateral adnexa. Laparoscopic resection of the mass was performed. Intraoperatively, an extraperitoneal glistening pelvic mass was discovered: the lesion was attached to the intrapelvic 1/3 middle portion of the left round ligament. Macroscopically, the mass measured 6 cm x 6 cm x 3.5 cm and exhibited a smooth and glistening external surface. On cut sections, the mass was an unilocular cyst filled with soft, yellow, amorphous material. Histologically, the cystic wall was lined by a stratified squamous epithelium with a granular cell layer. The cavity contained keratin-like material. The cystic wall showed numerous areas with close-set basaloid cells and pseudohorn cysts. The latter aspect consisted of cystic invaginations of the epithelium filled with surface keratin, which in a given microscopic section may be cut in cross-section, thereby appeared as "cysts" within the involved epithelium. Parietal rupture was present, accompanied by granulomatous inflammation. There were no postoperative complications, and the patient was discharged 3 days after the procedure. The present case is unique in that it is the first reported case of an extracutaneous seborrheic inclusion cyst arising from a very unusual site, namely the round ligament. The site of origin of the lesion and its cystic nature were established by computed tomography findings. Conservative treatment with enbloc resection was possible. Histological examination confirmed computed tomography findings. The present report described a lesion typically found in dermatopathology practice, but which had arisen in an extracutaneous site.

CTACK /CCL27 expression in psoriatic skin and its modification after administration of etanercept.

BACKGROUND: Tumour necrosis factor-alpha upregulates the expression of a cutaneous T cell-attracting chemokine (CTACK/CCL27), that promotes migration of cutaneous lymphocyte-associated antigen-positive lymphocytes into the skin. The role of CTACK/CCL27 in pathogenesis of psoriasis has recently been documented but no data are available at the present time on its modification in psoriatic cutaneous tissue after administration of etanercept. OBJECTIVES: To evaluate modifications of CTACK/CCL27 expression in skin of patients with psoriasis after administration of etanercept and their relation with disease activity. METHODS: Twenty-two patients with moderate to severe psoriasis underwent clinical, histological and immunohistochemical evaluations of disease activity at baseline and at 12 and 24 weeks after starting treatment with etanercept. RESULTS: All selected patients experienced an improvement of Psoriasis Area and Severity Index (PASI) score (P < 0.001) and Dermatology Life Quality Index score (P < 0.001) during the treatment. Skin histological abnormalities showed statistically significant modifications during treatment (P < 0.001). Immunohistochemical expression of CTACK/CCL27 decreased significantly (P < 0.001) and its relation with final PASI score was statistically significant (P < 0.05); the pattern of distribution of CTACK/CCL27 immunoreactivity significantly moved from diffuse and predominantly suprabasal to basal (P < 0.001) and the restoration of basal distribution of CTACK/CCL27 was also significantly related to clinical improvement of cutaneous disease (P < 0.001). CONCLUSIONS: Etanercept induces a clinical and histological improvement of psoriatic disease, promoting a reduction in CTACK/CCL27 cutaneous immunostaining and favouring the restoration of physiological CTACK/CCL27 epidermal expression. Moreover, CTACK/CCL27 reduction in cutaneous expression during administration of etanercept could be considered a favourable prognostic marker.