The 2015 World Health Organization Classification of lung tumors: new entities since the 2004 Classification.

In the last few years different new pulmonary neoplastic lesions have been recognised and some of them, namely NUT carcinoma, PEComatous tumors, pneumocytic adenomyoepithelioma, pulmonary myxoid sarcoma, myoepithelial tumors/carcinomas entered in the last 2015-WHO classification of lung tumors. In addition angiomatoid fibrous histiocytoma and ciliated muconodular papillary tumor have been morphologically and genetically characterized albeit not yet included in the 2015-WHO classification.In the present paper we summarised the clinical, morphological, immunohistochemical and molecular features of these new entities. The knowledge of key histologic and molecular characteristics may help pathologists in achieving a correct diagnosis thus leading to an adequate therapeutic approach.

Leiomyosarcoma of the female breast: report of two new cases and a review of the literature.

We present the clinical, light microscopic, and immunohistochemical features of two new cases of leiomyosarcoma of the female breast. Both the patients were old (83 and 86 years) and were referred with a history of a long-standing breast lump. The results of the physical examination and the preoperative radiologic investigations suggested a phyllodes tumor. The patients were treated with mastectomy. The tumors measured 6 and 6.5 cm in the largest dimension, respectively, and were composed of fascicles of atypical, actively proliferating spindle cells, often intersecting at right angles. The axillary lymph nodes were free of tumor. Immunohistochemically, the tumor cells were positive for desmin, muscle-specific actin, and vimentin and negative for other markers, including keratins and hormone receptors. Focal rhabdomyoblastic differentiation was noted in one case. Follow up at 1 year is negative for metastases or local recurrences. Our study confirms that leiomyosarcoma of the breast is a locally invasive neoplasm and that it could represent a peculiar anatomic entity among mesenchymal tumors of the breast.

Amyloidosis and diabetes in humans.

The relationship between amyloidosis and diabetes mellitus has been investigated with special regard to the islets of Langerhans. Little information is available in the literature about the relationship between diabetes mellitus and extrainsular amyloidosis. New data on the nature of amyloid and particularly its separation into two groups called "APUD-" and "Immunoamyloid" has induced us to reconsider the whole problem. The aim of this review is a reconstruction of the problem also on the basis of our experience.

Hodgkin's disease occurring in a Warthin's tumor: first case report.

The case of a Warthin's tumor whose lymphoid component was totally replaced by a malignant lymphoma, Hodgkin's type, is reported. The disease was characterized by a rapid downhill course, with repeated medullary relapses and subsequent episodes of bone marrow failure. Death occurred 13 months after the initial diagnosis and was due to severe visceral involvement by Hodgkin's lymphoma, as confirmed at post mortem examination.

Multicentric papillomavirus infection of the female genital tract. A study of morphologic pattern, possible risk factors and viral prevalence.

We have investigated 103 biopsy specimens obtained from 50 women (average 28.1 years, range 16-66) with multicentric condylomatosis of the genital tract, including the uterine cervix (48 samples), the vagina (23), and the vulva (32). Each patient had at least 2 biopsies. A positive in situ hybridization for a Human Papilloma Virus (HPV) cocktail was observed in samples from 38 patients: in these multiplicity of lesions regarded the cervix and vulva (22 cases), cervix and vagina (12), vulva and vagina (1), cervix, vulva and vagina (3). Viral types 6,11 were more prevalent in simple condylomata. Both low- and high grade lesions of cervix, vagina, and vulva showed prevalence of types 16, 18 and 31, 33, 35. Signaling for more than one probe cocktail was detected in 14 (13.6%) samples. Partner's condylomatosis was referred to by a sizeable minority of patients. It is concluded that the spectrum of HPV infection in the female genital tract reflects a multiplicity of factors, including involved viral type and site, immunitary reaction of the host, perpetration or reactivation of latent infections.

Aggressive "breast-like" adenocarcinoma of vulva.

A case of vulvar adenocarcinoma seen in a 42-year-old woman is reported. The tumor involved the right labium majus and diffusely spread into the surrounding soft tissues as well as the inguinal lymph nodes and was histologically composed of nests, cords, and tubular formations recalling an aggressive duct carcinoma of breast. Likewise, tumor cells exhibited positivity for common breast tumor markers, such as epithelial membrane antigen, carcinoembryonic antigen, and glandular keratins. The possible origin of the neoplasm from mammary ectopic tissue in vulva or from vulvar skin adnexa is briefly discussed.

Pseudoangiomatous hyperplasia of the mammary stroma: true entity or phenotype?

We report the clinical and pathologic features seen in 14 cases of pseudoangiomatous hyperplasia of the mammary stroma. The lesion manifested as a discrete palpable lump in twelve women and two men. The excisional biopsy specimens showed firm, circumscribed grey-tan lesions measuring from 3 to 5.5 cm in largest dimension. Histologic study revealed diffuse, anastomosing, enlongated slits with open lumina, covered by spindle cells with bland nuclei and no mitotic activity. Strong reactivity for vimentin and CD34 was noted. Smooth muscle actin was focally noted in most cases. Immunostains for other markers, including CD31 and factor VIII related antigen was negative. Spindle cells from two cases expressed both estrogen and progesterone receptors. In all the cases, there was some degree of glandular hyperplasia accompanying the stromal changes. Fibroadenoma or fibrocystic disease were also common features. Our study confirms that pseudoangiomatous hyperplasia of mammary stroma represents a proliferation of local myofibroblasts, likely related to a hormonal stimulus. The wide range of associated changes of breast parenchyma further indicates that this lesion may represent a local, non specific change rather than a true clinico-pathologic entity.

Metastatic tumors to the female breast. An autopsy study of 12 cases.

Twelve cases of metastatic tumors to the female breast are reported. Ten of them were incidentally discovered at autopsy; two cases were diagnosed ante mortem but one was misinterpreted as primary. The patients' mean age was 58 years. The metastasizing tumors included cutaneous malignant melanoma (four cases); ovarian, renal and gastric adenocarcinoma (two cases each); and individual cases of pulmonary and pancreatic carcinoma. The patients with melanoma were younger than the others (49.7 vs. 62.7 years). The results of the present study indicate that breast metastases, although rare, are not exceptional especially in large autopsy series. Their recognition in surgical material would result in more adequate treatment against the primary tumor, thereby avoiding unnecessary radical surgery to the breast.

Small cell carcinoma of lung simulating pleural mesothelioma. Report of 4 cases with autopsy confirmation.

Four cases of small cell carcinoma characterized by a striking involvement of the pleural sheets were investigated. The patients, four adult males with a long history of cigarette smoking, presented with symptoms common to pleural tumors, including cough and chest pain. Malignant cells were identified in pleural effusions of all cases and in the bronchial aspirate of one patient. Antitumoral treatments included chemo- and/or radiotherapy. Survival ranged from three to 17 months. At autopsy, the serosal sheets resulted to be extensively involved by thick tumor rinds, associated with massive hilar metastases. Histologically, the tumors were composed of small epithelial cells, expressing carcinoembryonic antigen and keratins and occasionally neuroendocrine markers. Our findings indicate that small cell carcinoma should be added to the group of pseudomesotheliomatous lung carcinomas and, above all, that it deserves distinction from ordinary mesothelioma, especially the small cell variant, because of its medico-legal implications and possible antitumoral treatment.

Inflammatory fibrosarcoma: another imitator of Hodgkin's disease?

We report a case of inflammatory fibrosarcoma occurring in a 49 year-old man, that manifested with distinct multinodular masses in the mesentery. Histologically, the lesion was characterized by spindle fibroblast-like cells, histiocytes, pool of lymphocytes and eosinophils, abundant fibrous to hyaline stroma, and numerous "ganglion" cells. Of special interest was the presence of large multinucleated tumor cells which displayed optically clear nuclei and prominent nucleoli, bearing a deceitful resemblance to the diagnostic Reed Sternberg cells of Hodgkin's disease. The differential diagnosis between the two conditions rests on the evaluation of the appropriate clinical background, as well as on an in-depth assessment of the basic pathologic features. Immunohistochemical reactivity of spindle and ganglion cells for actin along to complementary negativity for CD15, and CD30 further assists in separating the two conditions.

Histopathology of the frozen prostate. The microscopic bases of prostatic carcinoma cryoablation.

In the last few years percutaneous cryoablation surgery of the prostate has been re-introduced as an alternative means to treat prostatic carcinoma. Advantages of the technique include local effectiveness in eradicating tumors, minimal morbidity rate and lower costs when compared to radical surgery. We report a study documenting the histopathological changes seen in 317 biopsy specimens obtained from 30 patients (age range 59-83 years, median 73 years) treated with cryosurgical ablation for prostate cancer. Pre- and postoperatory assessment was inclusive of plain clinical, laboratory and instrumental data (digital rectal examination, transrectal ultrasound scan, serum prostatic specific antigen concentration) and systematic biopsies obtained from conventional and modified prostate sextants. Fifteen patients had tumors extending through the prostate capsule (pT3 and pT4). Six patients had stage PT1 tumors and 9 had stage pT2. Tissues were sampled at 3, 6 and between 12-18 months postoperatively. The histologic findings, in decreasing order of frequency, were: full core fibrosis, necrosis, granulation tissue, basal cell hyperplasia, cell swelling, hemosiderin deposits, chronic inflammation, thick nerves and prostatic hyperplasia. Necrosis was of the coagulative type, sometimes associated with nuclear debris, and seen at relatively short interval from cryotherapy. Fibrosis with hyaline qualities was seen especially at 12-18 month interval. The presence of necrosis, as well as granulation tissue, hemosiderin deposits and cell swelling, strongly correlate to intervals from cryosurgical ablation. Residual tumor tissue was focal (0.5-1 mm) and recognizable in 9 cores from 4 patients (13.3%) sampled especially from the prostatic apex. Incipient tumor necrosis was seen in 11 cores, without particular distribution. These findings indicate that cryosurgery results in distinctive changes in both tumoral and non-tumoral prostate tissue. Knowledge of the histopathologic patterns is important since it provides the clinicians with information on treatment efficacy or failure, and could assist in the selection of larger groups of patients eligible to cryosurgical ablation.

Aggressive fibromatosis of the larynx: report of a new case in an adult patient and review of the literature.

We describe a case of aggressive fibromatosis of the larynx occurring in a 75-year-old man. The lesion manifested with voice hoarseness and swallowing difficulty. A computerized tomographic scan of the neck revealed distortion of the glottic profile. A malignant tumor was suspected. Although a laryngoscopy-driven biopsy was non-diagnostic, total laryngectomy was done, since the lesion was not deemed amenable to conservative therapy. Grossly, the glottic rim was infiltrated by a hard, grey-white tissue showing a tentacular outline. Tissue sections featured a moderately cellular lesion composed of spindle cells with bland, tapered nuclei, enmeshed in a variably collagenized ground substance. Delicate spindle cell fascicles surrounded the native submucosal seromucous glands and had invaded the thyroid cartilage and the thyroid gland as well. The spindle cells were immunopositive for actins and vimentin, and negative for keratins, epithelial membrane antigen, desmin, and S-100 protein. No further therapy was administered. Periodic follow-up visits were negative. The patient died 5 years after surgery of myocardial infarction with no clinical evidence of lesion recurrence. Based on the available literature, our data confirm that laryngeal fibromatosis in adult patients is a locally infiltrating and progressive disease. Total laryngectomy with clear margins is needed as to avoid the high risk of local recurrence.

Gestational squamous cell carcinoma of the breast: an unusual mammary tumor associated with aggressive clinical course.

We report two cases of squamous carcinoma of the breast detected during the gestational period. One woman was post-partum and lactating; one was in the first trimester of pregnancy. The lesions were clinically palpable, multifocal, and measured more than 5 cm in their largest dimension; both had a cystic appearance. They were treated with radical mastectomy. One patient received pre-operatory chemotherapy. Histologically, the tumors were poorly differentiated squamous cell carcinomas. No areas of ordinary duct differentiation were seen. Lymph nodes contained metastatic squamous carcinoma in both cases. Tumor cells were negative for estrogen and progesterone receptors. Also, they expressed a high proliferative index and several markers of tumor progression, including cErb-B2, p53 protein, bcl-2, and epidermal growth factor receptor. One patient died of tumor 5 months following breast surgery and had extensive metastases proven at autopsy. The other patient had evidence of pulmonary metastases: following cisplatin therapy, she underwent clinical remission. This study shows that squamous carcinoma of the breast may occur in pregnant or lactating women: it appears clinically distinguishable from the non-gestational type that is usually associated with a better prognosis and occurs in peri- or postmenopausal women.

Association of breast cancer and meningioma. Report of 12 new cases and review of the literature.

We report 12 new cases of female breast cancer associated with intracranial meningiomas, inclusive of autopsy study. At the time of death the patients' age ranged from 52 to 95 years (average 70.6 years). Breast carcinomas were documented ante mortem in 11 cases and at autopsy in 1. Meningiomas were diagnosed at autopsy (10 cases) or in vivo (2 cases). The diagnosis of meningioma antedated that of mammary carcinoma in only one patient. Histologically, the cancers were of ductal (11 cases) and lobular infiltrating (1 case) types and showed a variable malignancy grade. Widespread extracranial metastases were present at autopsy in 7 cases. Brain metastases were seen in 1 case. Neurologic signs were referred in 4 subjects. Four breast cancers and one meningioma showed immunoreactivity for progesterone receptors, whereas all the cases were negative for estrogen receptors. In one case, metastatic breast carcinoma tissue was present within a psammomatous meningioma. A brief review of the literature, which includes 14 similar observations, is reported. Although the association of breast cancer and meningioma is still difficult to explain, its clinical implications are important and deserve proper attention. A proper work up in patients with suspected intracranial metastases is recommended so that resectable meningiomas are not mistaken for metastases.

Intrapericardial thymoma: report of two incidental autopsy cases and review of the literature.

OBJECTIVES: To report the pathologic features of intrapericardial thymoma and discuss their possible clinical relevance. DESIGN: Retrospective evaluation of autopsy cases and the available clinical records. SETTING: A large autopsy population (>31,000 postmortem examinations between 1980 and 1995) in an Italian general hospital. RESULTS: Two cases of thymoma showing an exclusive intrapericardial growth were retrieved from autopsy files. The patients were 61 and 82 years of age, both were women, and both were referred to the hospital with terminal conditions due to either neoplastic or chronic diseases. Myasthenia gravis and/or immunologic dysfunctions were not noted, although one of the patients had serum hypogammaglobulinemia. Roentgenography showed enlargement of mediastinal profiles and suggested cardiomegaly. At autopsy, tumors were bulky, noninvasive, and from 6 to 10 cm in largest dimension. Histologically, they were spindle cell "medullary" thymomas, frequently showing cell arrangement around microcystic spaces. They were strongly immunoreactive for epithelial markers. CONCLUSIONS: This study confirms that thymomas may occur in the pericardium. Tumor-related symptoms may be overlooked owing to concomitant heart disease or equivocal instrumental features, especially in the absence of immune system disturbances. Based on these premises, they may deserve a specific distinction in the expanding chapter of ectopic thymomas.

Intracranial metastases from malignant pleural mesothelioma. Report of three autopsy cases and review of the literature.

We report three cases of brain metastases from malignant pleural mesothelioma that were seen at autopsy. We present a summarized review of 15 similar reports that were previously published. Our study included three aged male patients with a long occupational history of heavy asbestos exposure. In two patients, the metastases were discovered incidentally at autopsy, and there were no neurologic symptoms referred to before death. In the other patient, who had clinically occult mesothelioma, the intracranial tumor was discovered ante mortem: in this patient, the clinical features, as well as a computed tomographic scan, suggested a primary tumor of the brain. Interestingly, the histologic features of the latter case that were seen at autopsy depicted a spindle cell tumor that focally exhibited pseudopalisading, necrosis, vascular buds, which deceptively recalled a glioblastoma. All the three cases shared a basic sarcomatous pattern of malignant pleural mesothelioma in both primary and metastatic tumors. The immunohistochemical profile was consistent with such interpretation. It was concluded that metastases to the brain from malignant pleural mesothelioma, although rare, are not exceptional even if their clinical relevance is not prominent. They are seen concomitantly with high-grade tumors, and by mimicking a primary tumor on a clinical, instrumental, and histologic ground, they may occasionally represent a potential source of diagnostic pitfall.

Aneurysmal bone cyst of the larynx presenting with hypoglottic obstruction.

We report a new case of aneurysmal bone cyst of the larynx occurring in a 22-year-old man. The lesion manifested with progressive breathing discomfort and appeared as a polypoid pedunculated mass attached to the subglottic mucosa. Microscopically, it featured numerous mononuclear and multinucleated giant cells surrounding cavernous spaces filled with blood. Foci of proliferating spindle cells and mature osteoid tissue could be recognized. There was no apparent relationship with the cricoid perichondrium. Clinical follow-up was negative for local recurrence. Based on this report and a review of the literature, we conclude that aneurysmal bone cyst of the larynx is phenotypically comparable to its bone homologue; however, its microscopic recognition may be difficult, especially on small biopsy fragments. Since it can be confused with several lesions, including telangiectatic osteosarcoma, awareness of this rare appearance of aneurysmal bone cyst is important to avoid unnecessary radical surgery.

The Value of Fine Needle Aspiration Cytology in Breast Fibromatosis: Study of Two New Cases and Review of the Literature.

We report two new cases of breast fibromatosis studied by needle aspiration cytology observed in a 32-year-old man and a 49-year-old woman. The lesions manifested as palpable, painless, and firm masses of the para-areolar breast soft tissues. Preoperative fine needle cytology revealed scant cellularity, featuring oval and spindle cells with bland nuclei and occasional larger polygonal cells with high nuclear:cytoplasmic ratio. Histologically, interwoven fascicles of spindle cells with bland nuclei, infiltrating the adjacent breast fat, were recognized. Based on available reports in the literature, we concluded that needle aspiration cytology, although not entirely specific, may be a source of important information in patients with breast fibromatosis. In particular, it confidently allows the exclusion of breast cancer and other more common diseases and is useful in planning a surgical approach to the lesion.

Papillary thyroid carcinoma of the thyroglossal duct cyst: comparative cytohistologic and immunochemical study of 2 new cases and review of the literature.

We report a cytohistologic and immunohistochemical study of 2 cases of papillary thyroid carcinoma occurring in a thyroglossal duct cyst. The patients were a 21-year-old woman and a 48-year-old man. Needle aspiration cytology smears were consistent with papillary thyroid carcinoma. The Sistrunk procedure was done. Papillary carcinoma was found within a thyroglossal duct cyst. In 1 case, the tumor spread outside the cyst. Follow-up was uneventful in both patients (2 and 9 years, respectively). Our results would indicate that papillary carcinoma of thyroglossal duct cyst, though indistinguishable from its thyroid homologue, has a more indolent course and could therefore be singled out as a clinicopathologic entity. Needle aspiration cytology reliably assists in planning patient management.

Time trends of benign/malignant breast biopsy ratios a multicenter Italian study.

AIMS AND BACKGROUND: Although they have been decreasing over time due to improved specificity of diagnostic assessment, benign biopsies of the breast are still common. Benign biopsies should be regarded as negative events, due to their economical and psychological cost and their possible negative impact on cosmesis and on further diagnostic evaluation. METHODS: Retrospective data on benign/malignant breast biopsies ratio (B/M) were collected in 9 Italian centers for a period of 10-15 years. The time trend of B/M and its association to age or to single centers was evaluated. RESULTS: Overall 31,001 cases were considered. A strong association of B/M to age was evident (average B/M values were 5.0, 1.3, 0.6, and 0.2 for women aged < 40, 40-49, 50-59, and > 59 years). A significant trend of decreasing B/M over time was observed only for one center. Age standardized B/M was significantly different (P < 0.000001) between centers, ranging between 0.34 and 1.69. Multivariate analysis confirmed an independent significant association of age and center to B/M. CONCLUSIONS: Marked differences in B/M are evident between centers, which cannot be explained by the confounding effect of age or by any apparent difference in the diagnostic protocol. The observed differences are likely ascribed to individual variations in diagnostic aggressivity. A progressive increase of the predictive value of calls for surgical biopsy may be achieved over time and centers with a high B/M should make every effort to optimize their performance. Acceptable (< 40 = 5, 40-49 = 1.5, 50-59 = 0.75, > 59 = 0.3) and desirable (2.5, 0.75, 0.35, 0.15) age specific reference standards for B/M are proposed.