A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review.

Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.

Metaplastic Matrix-Producing Carcinoma and Apocrine Lobular Carcinoma In Situ Associated with Microglandular Adenosis: A Unique Case Report.

Microglandular adenosis is a non-lobulocentric haphazard proliferation of small round glands composed of a single layer of flat to cuboidal epithelial cells. The glandular structures lack a myoepithelial layer; however, they are surrounded by a basement membrane. Its clinical course is benign, when it is not associated with invasive carcinoma. In around 30% of cases, there is a gradual transition to atypical microglandular adenosis, carcinoma in situ, and invasive breast carcinoma of several different histologic subtypes, including an invasive carcinoma of no special type, metaplastic matrix-producing carcinoma, secretory carcinoma, metaplastic carcinoma with squamous differentiation, acinic cell carcinoma, spindle cell carcinoma, and adenoid cystic carcinoma. Recent molecular studies suggest that microglandular adenosis is a non-obligate precursor of triple-negative breast carcinomas. In this manuscript, we present a unique case of microglandular adenosis associated with metaplastic matrix-producing carcinoma and HER-2 neu oncoprotein positive pleomorphic lobular carcinoma in situ with apocrine differentiation in a 79-year-old patient.

Tumor to Tumor Metastasis from Adenocarcinoma Not Otherwise Specified of the Parotid Gland to Uterine Leiomyoma: Presentation of a Unique Case.

Salivary gland adenocarcinoma not otherwise specified (NOS) is a malignant epithelial tumor composed of ductal/glandular structures with or without cystic formation. Histologically it is classified as high grade with relevant biological behavior. Although both minor and major glands may be involved, the majority (60%) implicate the parotid gland. Location, regional lymph node status, and histological grade are some of the factors that predict the progress of the disease and the development of metastases. Long follow-up is considered the standard option as distant metastases (DM) may occur despite regional control. Primary sites of DM, besides lymph nodes, include bone, lung, and liver. Herein we report a unique case of a 68-year-old female with a previous history of high-grade adenocarcinoma NOS of her right parotid gland. On her biannual follow-up examination, MRI revealed an abnormal increase in the size of a known uterine leiomyoma of the posterior uterine wall. Positron emission tomography-CT (PET-CT) showed increased uptake in the uterus and lungs. On frozen section, adenocarcinoma was found at the center of the leiomyoma. Histological and immunohistochemical findings were consistent with secondary involvement by the salivary gland adenocarcinoma NOS. Treatment consisted of cyclophosphamide, adriamycin, and cisplatin with poor outcome. The patient was lost to follow-up. Review of the literature indicates that no similar case has been reported in the English literature.

Primary squamous cell carcinoma of the ovary. Review of the literature.

PURPOSE: Primary squamous cell carcinoma (SCC) of the ovary is rare. Most cases arise from a cystic teratoma or less frequently from Brenner tumor or endometriosis. We reviewed 36 cases of primary ovarian SCC reported in the literature including a case diagnosed and treated in our institution. METHODS: Data was collected by using the key-words "primary squamous cell carcinoma" and "ovary" on Google Scholar and PubMed in April 2018. All reviewed cases were analyzed according to diagnosis, surgical approach, adjuvant therapy and outcome. RESULTS: To date 23 articles presenting 36 cases of primary ovarian SCC are reported. Nine patients had stage I, 8 stage II, 11 stage III and 5 stage IV disease, whereas 3 patients had in situ carcinoma. All patients underwent surgery (mainly hysterectomy with bilateral salpingo-oophorectomy). Adjuvant therapy was reported in 24 patients, 15 of which received chemotherapy, 6 radiotherapy and 3 a combination of both. Chemotherapy regimens were similar to the ones used in ovarian carcinoma (more often platinum plus paclitaxel). Follow-up period was in general short and survival varied between 9 days and 14 years, depending on the stage at diagnosis. CONCLUSIONS: Primary ovarian SCC is a rare entity with poor prognosis, compared to serous carcinoma. Treatment is usually extrapolated from classical ovarian carcinoma algorithms, including surgical management combined with adjuvant chemotherapy with or without radiotherapy. Further investigations are needed to define optimal treatment, such as chemotherapy regimens and the role of radiotherapy and lymph node dissection.

Invasive Lobular Carcinoma with Extracellular Mucin Production: Description of a Case and Review of the Literature.

Invasive lobular carcinoma of the breast is the second most common subtype of breast carcinoma. It accounts for 5-15% of the breast carcinoma cases reported. It shows a different metastatic pattern compared to invasive carcinoma of no special type. There are several variants of this cancer including the classic, solid, signet ring cell, tubulolobular, alveolar, trabecular, pleomorphic, and mixed subtypes each one with a distinctive morphology. Invasive lobular carcinoma has been associated with intracellular mucin production, in the form of intracytoplasmic lumina and signet ring cells whereas extracellular mucin production has been related to carcinomas of ductal origin. A new variant that displays extracellular mucin production was described recently. Only nineteen cases of this rare entity have been reported to date. In this manuscript, we report an additional case of invasive lobular carcinoma with extracellular mucin production, describing its clinico-pathological characteristics, and review the literature on the same.

Primary peripheral neuroectodermal tumor (PNET) of the adrenal gland: a rare entity.

PURPOSE: Ewing Sarcoma/Primitive Neuroectodermal Tumor (ES/PNET) is a malignant small round cell tumor belonging to the Ewing Sarcoma Family of Tumors. It occurs more commonly in children and young adults. Its localization in the adrenal gland is extremely rare. We reviewed 35 cases of ES/PNET of the adrenal gland reported in the literature and presented our case. METHODS: Data were collected by searching for ES/PNET and adrenal gland key words on Google Scholar and PubMed in March 2018, including a case diagnosed in our department. We analyzed all reviewed cases for diagnosis, surgical and systemic therapy and outcome. RESULTS: To date 24 articles presenting cases of ES/PNET of the adrenal gland are reported in the literature. We included in our review 35 cases previously described and one new case. Histologically all cases consisted of sheets of small round cells. Immunohistochemistry was also performed in all cases. Most cases stained positive for CD99 and negative for lymphocytic markers. Markers of epithelial differentiation displayed variable results. In all cases tested, characteristic translocations were displayed supporting the diagnosis. All patients but four were treated surgically and the majority received adjuvant therapy. Only very few cases received neoadjuvant chemotherapy. CONCLUSIONS: Primary ES/PNET of the adrenal gland is a rare tumor, showing specific morphological, immunohistochemical and cytogenetic characteristics. Treatment consists of surgery, chemotherapy and radiotherapy. Further investigations paired with long term follow-up are necessary to define prognosis for this rare entity.

Lymphoepithelioma-like breast carcinoma.

Nasopharyngeal lymphoepithelioma is an undifferentiated carcinoma in a dominated lymphoplasma-histiocyte stroma. Lymphoepithelioma-like carcinoma of the breast is the mammary counterpart of the lymphoepithelioma of the nasopharynx and is characterised by proliferation of poorly differentiated malignant cells within a prominent lymphoid infiltrate. It is a very rare primary carcinoma of the breast first reported in 1994 by Kumar and Kumar. Fewer than 40 cases have been reported in the English literature. In this manuscript a case of lymphoepithelioma-like carcinoma of the breast in a 57-year-old patient is reported along with a literature review on this rare entity.

Mucinous cystadenocarcinoma of the breast: the challenge of diagnosing a rare entity.

Mucinous cystadenocarcinoma is an extremely rare variant of primary breast tumor which is histologically similar to mucinous cystadenocarcinoma of the ovary and pancreas. Herein we report a case of a 63 years old woman diagnosed with diverse histological types of non-synchronous rare primary breast tumors, a medullary carcinoma of the right breast and a mucinous cystadenocarcinoma of the left breast. Macroscopically the neoplasm appeared multilocular filled with mucoid material. Under light microscopy the cystic areas were lined by columnar cells with abundant intracellular and extracellular mucin. Solid areas were composed of tall columnar cells with intracellular mucin. Moderate to marked atypia was noticed and tumor cells stained positive for cytokeratin 7 and negative for cytokeratin 20. Moreover tumor cells displayed a basal like immunophenotype expressed as followed: ER negative, PR negative, HER-2 negative, cytokeratin (CK5/6) positive and EGFR positive.

Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity.

BACKGROUND: Metalloproteinase 12 (MMP-12) is induced in chondrocytes during fetal development and malignant transformation. OBJECTIVES: The aim of our study is to examine the expression of MMP-12 in the cartilage and the subchondral bone of patients with osteoarthritis (OA) and to correlate its expression with disease severity and anthropometric characteristics. METHODS: Overall, 60 sections from 20 patients with idiopathic OA, were examined for the immunolocalization of MMP-12. As controls, we used the femoral heads of 4 patients treated with seniarthroplasty after fracture. Demographic characteristics and Body Mass Index (BMI) were calculated for all subjects. RESULTS: Specimens were divided into four groups based on the Mankin histological severity score. The immunohistochemical study showed MMP-12 expression in the cartilage and subchonral bone of OA patients, while there was no expression in normal controls. At the moderate OA changes (Mankin score: 6-7), MMP-12 was detected mainly at the matrix of fibrocartilage tissue. During disease progression, MMP-12 was expressed at the sides of the cartilage and bone erosion and in the bone cysts. Furthermore, it was traced in the osteocytes of the subchondral bone. Osteoblast-like cells and bone lining cells express MMP-12 during the stage of severe OA (Mankin: ≥8). Osteoclasts expressing MMP-12 were also detected in the group of severe OA. Interestingly, MMP-12 expression was positively correlated with the age and the BMI of OA patients. CONCLUSION: The increased expression of MMP-12 in the bone-cartilage unit of OA patients suggests a possible role in OA pathogenesis and progression. LEVEL OF EVIDENCE: III, prospective comparative study.

Encapsulating peritoneal sclerosis with favorable outcome in hemodialysis: an unusual case with a literature review.

Encapsulating peritoneal sclerosis is a rare condition of a poorly understood pathogenesis with recognized risk factors, such as medications, surgical interventions, systemic diseases, and malignancies. In endstage renal disease it has been associated with chronic peritoneal dialysis. We hereby report the case of a 59-year-old male hemodialysis patient, who was never treated with peritoneal dialysis and developed an unexplained massive ascites 4 months post laparoscopic cholecystectomy for gallstones. A second laparoscopy and histological evaluation revealed encapsulating peritoneal sclerosis-like findings with parietal peritoneum and spleen involvement. The patient was successfully treated for 12 months with prednisone and tamoxifen. Possible pathogenetic mechanisms of the disease in this case are discussed including peritoneal irritation by chronic cholecystitis, low-grade inflammation of hemodialysis, intraoperative complications and the hypothetical role of oxidized regenerated cellulose used for hemostasis. In conclusion, the suspicion of peritoneal sclerosis should be encountered in cases of unexplained ascites in patients undergoing hemodialysis. The early diagnosis includes laparoscopy and histological evaluation and can result in a good outcome under medical treatment; otherwise, there is a high possibility of bowel obstruction with fatal outcome.

A rare case of an inflammatory myofibroblastic tumor in a middle-aged female.

Inflammatory myofibroblastic tumors (IMTs) are distinct entities with specific characteristics immunohistochemically and molecularly. They are regarded as "intermediate malignancy" tumors of unknown etiology. We report a case of a 64-years-old woman with a fever and abdominal discomfort for 3 months; a computer tomography was performed indicating gastrointestinal stromal tumor. Histologically the lesion proved to be IMT of the abdomen.

Effect of autologous platelet-rich plasma in combination with a biphasic synthetic graft material on bone healing in critical-size cranial defects.

PURPOSE: The aim of the study was to investigate the effect of autologous platelet-rich plasma (PRP) on the osteogenic potential of a biphasic synthetic graft material composed of hydroxyapatite and beta-tricalcium phosphate (HA/ß-TCP) in critical-size cranial defects in rabbits. MATERIALS AND METHODS: Three circular bicortical critical-size cranial defects were created in each of 18 rabbits. The first of the defects was grafted with autologous PRP and HA/ß-TCP, the second was grafted with HA/ß-TCP without PRP, and the third was left unfilled as a negative control. Animals were euthanized at 2, 4, and 6 weeks after surgery. Harvested tissue specimens were evaluated histologically and histomorphometrically. Several parameters associated with osteoclastic and osteoblastic activities were measured and calculated. The results were statistically analyzed using the 1-way analysis of variance statistical method. RESULTS: Histologic analysis of the samples showed bone tissue formation at all experimental sites including untreated control defects. A statistically significant difference in new bone formation between the defects treated with HA/ß-TCP + PRP and defects treated with HA/ß-TCP alone was not observed. Control untreated defects showed the greatest bone regeneration. CONCLUSIONS: In this animal model, autologous PRP had no effect on bone healing in addition to a biphasic HA/ß-TCP synthetic graft material after 2, 4, and 6 weeks of implantation.

Expression of matrix metalloproteinase-1 (MMP-1) in Wistar rat's intervertebral disc after experimentally induced scoliotic deformity.

INTRODUCTION: A scoliotic deformity on intervertebral discs may accelerate degeneration at a molecular level with the production of metalloproteinases (MMPs). In the present experimental study we evaluated the presence of MMP-1 immunohistochemically after application of asymmetric forces in a rat intervertebral disc and the impact of the degree of the deformity on MMP-1 expression. MATERIAL-METHOD: Thirty female Wistar rats (aged 2 months old, weighted 200 ± 10 grams) were used. All animals were age, weight and height matched. A mini Ilizarov external fixator was applied at the base of a rat tail under anaesthesia in order to create a scoliotic deformity of the intervertebral disc between the 9th and 10th vertebrae. Rats were divided into three groups according to the degree of the deformity. In group I, the deformity was 10°, in group II 30° and in group III 50°. The rats were killed 35 days after surgery. The discs were removed along with the neighbouring vertebral bodies, prepared histologically and stained immunohistochemically. Immunopositivity of disc's cells for MMP-1 was determined using a semi-quantitative scored system. RESULTS: MMP-1 immunopositivity was detected in disc cells of annulus fibrosus of all intervertebral disc specimens examined. The percentage of MMP-1 positive disc cells in annulus fibrosus in group I, II and III were 20%, 43% and 75%, respectively. MMP-1 positivity was significantly correlated with the degree of the deformity (p < 0,001). An increase of chondrocyte-like disc cells was observed in the outer annulus fibrosus and at the margin of the intervertebral disc adjacent to the vertebral end plates. The difference in the proportion of MMP-1 positive disc cells between the convex and the concave side was statistically not significant in group I (p = 0,6), in group II this difference was statistically significant (p < 0,01). In group III the concave side showed a remarkable reduction in the number of disc's cells and a severe degeneration of matrix microstructure. CONCLUSION: The present study showed that an experimentally induced scoliotic deformity on a rat tail intervertebral disc results in over-expression of MMP-1, which is dependent on the degree of the deformity and follows a dissimilar distribution between the convex and the concave side.

Primary synovial chondrosarcoma of the hip joint in a 45-year-old male: case report and literature review.

Synovial chondrosarcoma is a rare tumor, seen most commonly arising from antecedent synovial chondromatosis, the more common benign entity. The distinction between the two can be difficult on the basis of clinical, imaging, and histologic criteria. The authors report a case of pathologically proven synovial chondrosarcoma of the hip in a 45-year-old male initially treated for presumed synovial chondromatosis. The case is made more unusual by the fact that no evidence of co-existent synovial chondromatosis was noted at histology. The literature as regards synovial chondrosarcoma, both de novo and secondary cases, is reviewed.

A hemangioma on the floor of the mouth presenting as a ranula.

A painless, bluish, submucosal swelling on one side of the floor of the mouth usually indicates the presence of a ranula. Rarely, such a swelling may be caused by an inflammatory disease process in a salivary gland, a neoplasm in the sublingual salivary gland, a lymphatic nodular swelling, or embryologic cysts. We report a patient with swelling in the floor of her mouth that was clinically diagnosed as a ranula. Suspicion arose during surgery that it was a vascular tumor and, on histologic testing, the swelling was confirmed to be a hemangioma. To our knowledge, this is the first report in the literature of a hemangioma presenting as a ranula.

Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma.

BACKGROUND AND OBJECTIVES: To investigate the immunohistochemical expression of three apoptosis-related genes (bax, bcl-2, and p53) and apoptosis (TUNEL) in patients with primary osteosarcoma, and examine potential correlations between gene expression and clinicopathological characteristics in these patients. MATERIALS AND METHODS: Thirty-five primary osteosarcoma specimens and 18 tissue specimens deriving from non-malignant osseous lesions were immunohistochemically stained for bax, bcl-2, and p53 proteins, while apoptosis was investigated by the TUNEL method. The results were statistically analyzed. RESULTS: P53, bax, and bcl-2 protein expression was observed in 22 (62.9%), 29 (82.9%), and 18 (51.4%) osteosarcoma patients, respectively. Non-specific positive TUNEL staining (+/-) was observed in two primary osteosarcoma cases (5.7%). None of the benign controls expressed any of the genes studied. None of the apoptosis-related genes studied was able to predict overall or disease-free survival in our group of patients. Nevertheless, increased bax/bcl-2 protein expression ratio was associated with a decreased 4-year survival and disease free survival (P = 0.0229 and P = 0.0370, respectively). Furthermore, all the patients who were bax(+)/bcl-2(-)/p53(+) relapsed within the 4-year follow-up period (P = 0.0385). CONCLUSIONS: The increased apoptotic rate as determined by an elevated bax/bcl-2 protein expression ratio or by the bax(+)/bcl-2(-)/p53(+) protein expression pattern, appears to identify groups of osteosarcoma patients with unfavorable prognosis.

Vanishing bone disease: review and case reports.

Vanishing bone disease is a rare idiopathic disease, leading to extensive loss of bony matrix, replaced by proliferating thin-walled vascular channels and fibrous tissue. There are >191 cases reported in the English literature. Gorham and Stout made the first overview of the disease in 1955 and they first presented 24 cases known at that time. The etiology remains speculative, the prognosis unpredictable, and effective therapy still unknown. The disease can be monostotic or polyostotic although multicentric involvement is exceptional. We report 2 cases of a histologically studied vanishing bone disease involving the humerus and the femoral head. The patients' past history was noncontributory. The radiographic study revealed a destructive lesion of the left humerus in the first case, and complete disappearance of the femoral head in the second case. Laboratory findings including hormonological tests revealed no evidence of metabolic, immunologic, neoplastic, or infection etiology. Histopathological findings of the 2 cases revealed thickened bone of lamellar structure without marrow cavities next to fibrous tissue, with few fibroblasts and a small number of newly formed vascular channels. The prognosis varies from slight disability to death by involvement of vital skeletal structures. The treatment of vanishing bone disease is controversial. Several treatment modalities have been proposed. Surgical intervention has been suggested as a method of choice by many authors and concerns local resection of the affected bone, with or without replacement prosthesis or bone grafts.

Prognostic value of bax, cytochrome C, and caspase-8 protein expression in primary osteosarcoma.

The prognostic significance of bax, cytochrome c, and caspase-8 in patients with primary osteosarcoma is unknown. We examined the immunohistochemical expression of these genes in 35 surgically treated patients with primary osteosarcoma. Clinicopathological and survival data were correlated with the staining result. Eighteen tissue specimens from non-malignant osseous lesions were used as controls. Bax, cytochrome c, and caspase-8 positive staining was observed in 29 (82.9%), 16 (45.7%), and 0 (0%) patients, respectively, but did not stain any of the 18 benign osseous lesions used as controls. None of the genes studied predicted overall or disease-free survival. Patients, however, bearing bax(+)/cytochrome c(+) or bax(+)/cytochrome c(+ +) tumors had a decreased 4-year disease-free survival rate compared to the rest of the group (p = 0.0489 and p = 0.0208, respectively), identifying two groups of patients where more intensive adjuvant treatment could possibly be applied to prevent high postoperative recurrence rates.

Osteoid osteoma of the radial styloid mimicking de quervain tenosynovitis.

A very unusual location of osteoid osteoma arising in the radial styloid is presented, which strongly mimicked de Quervain tenosynovitis, thereby resulting in the patient undergoing an additional unnecessary operation and a substantial delay of more than 2 years in diagnosis.

Dysplasia epiphysealis hemimelica (Trevor disease): a rare developmental disorder of bone mimicking osteochondroma of long bones.

Dysplasia epiphysealis hemimelica (DEH) is a rare developmental disorder of childhood and is characterized by asymmetric enlargement of the epiphyseal cartilage of the long bones. After 4 to 5 years of age, the lesions histologically resemble osteochondroma. To our knowledge, only one publication of this entity is available in an English pathology journal. The clinical, radiographic, and histologic features of 9 cases of DEH were retrospectively reviewed. The patients' age ranged from 3 to 15 years with single or multiple lesions of the femur, fibula, tibia, and talus. The etiology and pathogenesis of DEH are not known. Its origin and evolution has initially apparent similarities to the development and growth of epiphyseal secondary ossification centers. DEH can be differentiated from osteochondroma of long bones using clinical, radiologic, and pathologic parameters. DEH occurs in young children and adolescents manifesting as lesions that arise particularly from the epiphysis of the lower extremities and tarsus. Osteochondroma, in contrast, occurs most frequently between 10 and 30 years of age and originates from the metaphysis of long bones. Although the DEH cartilage resembles osteochondroma, there are several significant histologic differences. During infancy, lesions of DEH histologically reveal osteocartilaginous nodules that resemble secondary ossification centers. Usually after 4 to 5 years of age they develop into osteochondroma-like lesions. Although all cases of DEH contain small areas of calcified cartilage beneath the cartilage cap, a significant percentage of osteochondromas show large amounts. The nodules and cartilage cap of DEH contain bands of cartilage separating areas of cancellous bone; these bands are not present in osteochondroma. Among the other distinguishable features, recent molecular studies of DEH demonstrated normal expression levels of EXT1 and EXT2 genes, comparable to that of normal growth plate. Osteochondroma, in contrast, has low levels of EXT1 and EXT2 gene expression due to gene mutation. The histologic differences in combination with the distinct clinical and radiographic features should enable a pathologist to differentiate these entities.