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.

Megaduodenum: an unusual presentation of amyloidosis?

Amyloidosis, a potentially fatal disease, is characterized by an abnormal deposition of autologous proteins. Heart, liver, kidneys, lung, thyroid, skin and the gastrointestinal tract can be involved; in this last case mucosal alterations or disturbances of the motility leading to pseudo-obstruction, bleeding, diarrhea and malabsorption can be present. However, the data concerning the possible gastrointestinal presentations of amyloidosis are scanty and heterogeneous. We report the case of a patient presenting severe gastrointestinal symptoms caused by a megaduodenum. The patient was thoroughly investigated and lesions appeared limited to the upper gastrointestinal tract in the absence of a systemic disorder. However, at follow up the patient developed cardiac dilatation and bioptic samples revealed the presence of amyloidosis.

[Clinicopathologic correlations in acute renal graft rejection]. / Aspetti clinico-patologici del rigetto acuto nel trapianto renale.

Although the diagnostic and therapeutic outcome of renal transplantation has successfully improved during the last decades, acute graft rejection (AGR) is still an ongoing cause of concern being often associated with irreversible graft dysfunction. Renal biopsy remains a valuable tool in the initial assessment of the potential graft malfunction especially during the early post-transplant period. It is an accurate and sensitive means for detecting prognostically relevant microscopic abnormalities, and assisting in subsequent patient management. For long time, the histopathologic evaluation of AGR has suffered from an irreducible bias with poor interobserver rates. Nowadays, the classification schemes of AGR include the BANFF approach and the National Institute of Heath Collaborative Clinical Trials in Transplantation (NIH-CCTT) system: both have been originally designed in order to improve the diagnostic reproducibility of AGR among pathologists. Arteritis and tubulitis, along to clinical information, constitute the cardinal features of the BANFF classification. Distinguishing features of the traditional NIH-CCTT system includes microscopic criteria such as assessment of interstitial hemorrhage, extent and quality of inflammatory infiltrate, and acute glomerulitis, in addition to tubulitis and arteritis. The BANFF classification has apparently gained more popularity than the time-honored NIH-CCTT system since, if used in the appropriate clinical context, it allows a more accurate assessment of AGR, provides prognostically relevant information, and has a better reproducibility rate among pathologists. Nevertheless, the accuracy trend has not significantly improved during the last few years.

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.

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.

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.

Role of fine-needle aspiration cytology in nonpalpable mammary lesions: a comparative cytohistologic study based on 308 cases.

We retrospectively evaluated the accuracy of fine-needle aspiration cytology (FNAC) in nonpalpable breast lesions detected by imaging techniques between 1995-1997. A total number of 308 lesions was investigated: 273 had been studied by means of either FNAC obtained under ultrasound (175 cases) or stereotactic guidance (98 cases). The overall sensitivity rate was 87.8%; specificity was 95.3%; the positive predictive value was 76.6%; the negative predictive value was 97.8%. Our results confirm that FNAC is quite effective in the approach to patients with nonpalpable breast lesions. It is particularly accurate in diagnosing malignancy, although a lower yield may be encountered in tumor types producing a desmoplastic stroma (tubular carcinoma, infiltrating lobular carcinoma) or in noncomedonic in situ ductal carcinoma. Discrepancy between a suspicious cytology and a negative histology is more frequent with benign lesions usually because of sampling mistake or technically inadequate smears. In particular, when smears are adequate, FNAC safely assists in ruling out the malignant lesions.

Embryonal "Botryoid" rhabdomyosarcoma of the larynx: a clinicopathologic and immunohistochemical study of two cases.

Two cases of embryonal rhabdomyosarcoma of the larynx are reported. The tumors occurred in a 16-year-old boy and in a 66-year-old man. They manifested clinically with nonspecific symptoms, including voice hoarseness and sense of throat fullness. Treatment consisted of total and partial laryngectomy, respectively. Grossly, both lesions had an exophytic growth pattern and microscopically featured a proliferation of small round to oval cells. Cell cytoplasms were occasionally stainable and fibrillary. Quite often, tumor cellularity was denser beneath the covering mucosa, recalling a "cambium layer" pattern. Tumor cells immunoreacted for desmin, actins, myoglobin, and sarcomeric actin; no immunostaining was noted for epithelial markers. No further antitumoral treatment was administered after surgery. There has been no recurrence of tumor at 2 and 10 years, respectively. Based on our series and the available literature, it seems that rhabdomyosarcoma of the larynx pursues a less-aggressive course than that seen in the homonimic juvenile or adult soft tissue lesion. Surgery alone appears to be a valid treatment option, especially when a polypoid, or "botryoid" gross pattern, coupled with the embryonal small cell histotype is encountered. In light of these findings, it is suggested that botryoid rhabdomyosarcoma of the larynx may deserve a specific consideration among the various laryngeal mesenchymal malignancies.

Pulmonary thromboembolism following calf cellulitis: report of an unusual complication of dog bite.

We report a case of a 75-year-old woman who died of pulmonary thromboembolism following a dog bite to the calf. The bite caused laceration of the skin and gangrenous cellulitis of leg soft tissues. Six days after hospitalization, the patient died suddenly, despite early antibiotic and heparin administration. Postmortem examination revealed extensive thrombosis of the deep veins of the calf and massive thromboembolism of the main pulmonary arteries.

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.

Polypoid osteosarcoma of the left atrium: report of a new case with autopsy confirmation and review of the literature.

We describe a new case of heart osteosarcoma manifesting as a large polypoid mass of the left atrium. Clinically, the lesion presented with dyspnea, syncopal attacks, and fever. Ultrasound scans of the heart were suggestive of a cardiac myxoma, although some imaging features could retrospectively indicate a malignant neoplasm. In particular, the lesion was relatively immobile, did not show the characteristic myxoma motion during the heart cycle, and extended into the left pulmonary veins. Exploratory thoracotomy showed a nonresectable polypoid mass of the left atrium widely infiltrating the myocardium and the epicardium, histological features of a polymorphic sarcoma. The patient died 5 months after presentation with diffuse metastases. At autopsy, a 5-cm polypoid tumor was seen protruding into the left atrium. Neoplastic infiltration of the atrial myocardium, pericardium, and pulmonary veins was evident. Extensive metastatic deposits were observed in numerous sites, including the skin, lung, liver, and brain. Microscopically, a spindle cell sarcoma forming malignant osteoid was seen, admixed with areas indistinguishable from myxoid and pleomorphic malignant fibrous histiocytoma. This case provides further evidence that although rare, osteosarcoma of the heart usually presents as a polypoid mass of the left atrium and is histologically characterized by conspicuous polymorphism. It is associated with a poor prognosis and rapid appearance of distant metastases. Although at echocardiography it may mimic a myxoma, subtle features such as tumor extension into pulmonary veins and main origin from nonseptal atrial walls suggest the presence of a nonmyxomatous tumor and a preoperatory diagnosis of aggressive malignant disease.

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.

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.

Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating malignant pleural mesothelioma.

We report two cases of autopsy confirmed angiosarcoma in adult males, presenting as diffuse pleuropulmonary tumours and simulating malignant mesothelioma. Both the lesions grew along the serosal surfaces and were characterized by variably thick rinds of tissue encasing the lung. The pulmonary parenchyma showed diffuse, dark red, subpleural consolidations and multiple cavitations. Histologically, the lesions were composed by atypical spindle and polygonal, epithelioid cells showing rudimentary vascular differentiation and exhibiting strong positivity for factor VIII, CD31, CD34 and vimentin, We conclude that angiosarcoma may present with preponderant or exclusive involvement of pleura and peripheral lung and that it should be added to the list of tumours capable of simulating malignant mesothelioma.

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.

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.

Small cell carcinoma of the liver: a hitherto unreported variant of hepatocellular carcinoma.

We report three cases of an unusual primary carcinoma of the liver composed of small cells. The patients were adult males (56 to 89 years) who presented with jaundice, weight loss and abdominal discomfort. Surgery was attempted in one case. Clinical evolution was rapid, with death ensuing between 1 and 5 months after diagnosis. Surgical (1 case) and autopsy (2) tissues were available for review. All three tumours arose in non-cirrhotic livers. They were composed of broad nests of small epithelial cells with little supporting tissue. They were positive for low-molecular weight keratins and alpha-fetoprotein. One case was immunoreactive for erythropoietin antigen. Expression of neuroendocrine markers was focal and erratic. No immunostaining was observed for carcinoembryonic antigen or S-100 protein. In one case ultrastructural investigation disclosed canaliculi surrounded by microvilli and junctional complexes. In the light of these features, it appears that small cell carcinoma represents a rare, but definite variant of hepatocellular carcinoma. Although it does not segregate in a peculiar clinical setting, it should be distinguished from metastatic pulmonary small cell carcinoma as well as from other malignancies featuring small cells.

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.

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.

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.