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Journal: Annals of diagnostic pathology


The aim of this study was to determine the impact of prognostic factors in primary fallopian tube carcinoma (PFTC). All cases of PFTC diagnosed between 1990 and 2010 were retrieved from the files of 6 academic centers. The cases were staged according to a modification of the International Federation of Obstetrics and Gynecology staging system proposed by Alvarado-Cabrero et al (Gynecol Oncol 1999; 72: 367-379). One hundred twenty-seven PFTC cases were identified. The mean age of the patients was 64.2 years. Stage distribution was as follows: 72 (57%), stage I; 19 (15%), stage II; 28 (22%), stage III; and 8 (6.2%), stage IV. Depth of infiltration of the tubal wall was an independent prognostic factor in stage I cases (P < .001). Carcinomas located in the fimbriated end even without invasion had a worse prognosis than did carcinomas involving the tubal portion of the organ. The presence of vascular space invasion correlated with the depth of tubal wall invasion (P = .001) and the presence of lymph node metastases (P = .003). Tumor grade significantly correlated with survival (P < .0001), but histologic type was of marginal significance and only if it was grouped as nonserous/non-clear cell vs serous/clear cell (P = .04). The depth of invasion of the tubal wall and the presence of carcinoma in the fimbriated end even without invasion are important prognostic indicators. The modified International Federation of Obstetrics and Gynecology staging system should be used on a routine basis in all carcinomas of the fallopian tube.

Concepts: Cancer, Lung cancer, Cancer staging, Lymph node, Gynecology, Prognosis, Fallopian tube cancer, Obstetrics and gynaecology


Our aim was to describe clinicopathologic features of secretory carcinoma on a cohort of cases. We retrieved reported cases of secretory carcinoma of breast (SCB) in the Section of Histopathology, Department of Pathology & Microbiology, Aga Khan University Hospital Karachi, from May 2004 to December 2011. The slides were reviewed, and clinicopathologic features were noted. A total of 8 cases of SCB were found. The age ranged from 17 to 60 years (median, 41 years) with a female to male ratio of 7:1. Lumpectomy was done in 6 cases, and mastectomy, in 2 cases. The tumor size ranged from 2.5 to 10 cm (mean, 5.5 cm). Histologically, abundant extra- and intracellular secretory material was seen in all cases. Most of the tumors showed mixtures of patterns with dominant microcystic and papillary patterns. In situ component was seen in only 1 case. Lymph node metastases were seen in both cases with lymph node sampling. In conclusion, SCB is a rare type of ductal breast carcinoma. The papillary pattern of SCB is rare according to published data but was seen in most of our cases. In situ secretory carcinoma is even rarer, and to date, we have seen a single case only. Although most occur in women, these can be seen in men as well.

Concepts: Cancer, Breast cancer, Metastasis, Carcinoma in situ, Lymph node, Anatomical pathology, Aga Khan IV, Karachi


Osteoid osteoma and osteoblastoma are histologically similar, benign bone-forming tumors. In this retrospective study, we aimed to evaluate the natural history; clinical, pathologic, and radiologic findings; and treatment results in 204 patients between 1959 and 2006 in a single institution. According to the World Health Organization’s definition, tumors ≤1 cm in diameter were classified as osteoid osteoma, and those ≥2 cm, as osteoblastoma. For tumors between 1 cm and 2 cm, other criteria, such as the bone involved, the site, the presence of a nidus, and presence of peripheral sclerosis, were used for diagnosis. There were 131 patients with osteoid osteoma (93 male, 38 female) and 73 patients with osteoblastoma (40 male, 33 female). The mean age in the osteoid osteoma and osteoblastoma groups was 16.4 ± 7 and 19.6 ± 9.9 years, respectively. The osteoid osteoma cases were mostly localized in the extremities, whereas the osteoblastoma cases involved the vertebral column and sacrum. The nidus size varied between 0.2 and 1.5 cm in osteoid osteoma cases, and the tumor size range was 1.3-10 cm in the osteoblastoma cases. The pain was encountered in 89% of osteoid osteoma and 45% of osteoblastoma patients. Histopathology was similar in both cases. The treatment of choice was conservative surgery for both diagnoses. In conclusion, osteoblastoma is clinically and radiologically more aggressive than osteoid osteoma.

Concepts: Cancer, Pathology, Anatomical pathology, Vertebral column, Retrospective, Benign tumor, World Health Organization, Osteoid osteoma


Leukemic, non-nodal mantle cell lymphoma (MCL) is a relatively indolent disease characterized by asymptomatic leukemic presentation, non-nodal disease distribution, and slow disease progression, particularly in comparison to that of classic nodal MCL. We studied 3 cases of leukemic, non-nodal MCL in which TP53, ATM, and/or 13q14 deletions were identified. All three patients had disease progression leading to treatment requirements in two of the patients at 5 and 18 months after initial diagnosis. The third patient also clinically progressed 25 months after initial diagnosis but was lost to follow up despite recommendation for initiation of therapy. We present these cases as potential evidence that while leukemic non-nodal MCL is typically an indolent disease compared to classically defined mantle cell lymphoma, cytogenetic heterogeneity exists and cases with TP53, ATM, and/or 13q14 deletions may have a relatively aggressive clinical course.

Concepts: Cancer, Medical terms, Chronic myelogenous leukemia, Mantle cell lymphoma


Understanding the metabolic profile of neurons with the hyperphosphorylated tau protein characteristic of Alzheimer’s disease is essential to unraveling new potential therapies and diagnostics for the surgical pathologist. We stratified 75 brain tissues from Alzheimer’s disease into hyperphosphorylated tau positive or negative and did co-expression analyses and qRTPCR for importin-β and exportin-5 plus several bcl2 family members and compared the data to controls, Down’s dementia and Parkinson’s disease. There was a significant increase in the expression of importin-β and exportin-5 in Alzheimer’s disease relative to the three other categories (each p value<0.0001) where each protein co-localized with hyperphosphorylated tau. Both apoptotic and anti-apoptotic proteins were each significantly increased in Alzheimer's disease relative to the three other groups. Neurons with hyperphosphorylated tau in Alzheimer's disease have the profile of metabolically active cells including increased exportin-5 and importin-β mRNA and proteins which indicates that immunohistochemistry testing of these proteins may aid the surgical pathologist in making a definitive diagnosis.

Concepts: Alzheimer's disease, Protein, Medicine, Cancer, Metabolism, Anatomical pathology, Parkinson's disease, Dementia


The odontogenic keratocyst (OKC) remains the most challenging jaw cyst to treat because of its locally-aggressive behaviour and high recurrence potential. Emerging evidence suggests that osteopontin, its receptors CD44v6 and integrin αv, and podoplanin, have a role in the local invasiveness of this cyst. However the spatial distribution characteristics of these pro-invasive markers in the lining epithelium of OKC, and their association with the clinicopathologic parameters of OKC are largely unexplored. This study sought to address these issues in comparison with dentigerous cysts (DCs) and radicular cysts (RCs) and to evaluate their biological relevance.

Concepts: Cyst, Dentigerous cyst


Due to the fact that mitochondrial defects and oxidative stress have been related with obesity and breast cancer is more aggressive in women with obesity, we investigated if postmenopausal Mexican-Mestizo women with breast cancer presented somatic mutations in the sequence of the ATP6 and/or ND3 genes. Twenty one postmenopausal Mexican-Mestizo women with breast cancer who underwent mastectomy or breast conserving surgery were studied. Height and weight were used to calculate body mass index. DNA from tumor tissue samples and blood leukocytes was amplified by polymerase chain reaction and sequenced the ATP6 and ND3 mitochondrial genes. Ages ranged from 46 to 82. According to World Health Organization criteria among the 21 women, 7 had a normal BMI, 7 were overweight and 7 had obesity. In regard to the molecular study, after sequencing the coding region of ATP6 and ND3 genes of the DNA obtained from both leukocytes and tumor tissue, we did not find somatic mutations. All of the changes that we found in both genes were polymorphisms: in ATP6, we identified in ten patients 3 non-synonymous nucleotide changes and in ND3 we observed that six patients presented polymorphisms, three of them were synonymous and two non-synonymous. To our knowledge, this constitutes the first report where the complete sequence of the ATP6 and ND3 genes has been analyzed in postmenopausal Mexican-Mestizo women with breast cancer and diverse BMI. Our results differ with those reported in Caucasian and Asian populations, possibly due to ethnic differences.

Concepts: DNA, Cancer, Breast cancer, Molecular biology, Obesity, Estrogen, Body mass index, DNA replication


Acute reoviral infection has been extensively studied given the virus’s propensity to target malignant cells and activate caspase-3 mediated apoptosis. Reovirus infection of malignant N1E-115 mouse neuroblastoma cells led to significant increased expression of importin-β and exportin-5 mRNAs (qRTPCR) and proteins (immunohistochemistry) which was partially blocked by small interfering LNA oligomers directed against the reoviral genome. Co-expression analysis showed that the N1E-115 cells that contained reoviral capsid protein had accumulated importin-β and exportin-5, as well as activated caspase 3. Reoviral oncolysis using a syngeneic mouse model of multiple myeloma similarly induced a significant increase in importin-β and exportin-5 proteins that were co-expressed with reoviral capsid protein and caspase-3. Apoptotic proteins (BAD, BIM, PUMA, NOXA, BAK, BAX) were increased with infection and co-localized with reoviral capsid protein. Surprisingly the anti-apoptotic MCL1 and bcl2 were also increased and co-localized with the capsid protein suggesting that it was the balance of pro-apoptotic molecules that correlated with activation of caspase-3. In summary, productive reoviral infection is strongly correlated with elevated importin-β and exportin-5 levels which may serve as biomarkers of the disease in clinical specimens.

Concepts: DNA, Protein, Gene, Cancer, Virus, Apoptosis, Bcl-2, Caspase 3


Core needle biopsy (CNB) has been used as an alternative or a complementary method for diagnosis of thyroid nodules. However, morphological analysis of the nuclear features of papillary thyroid carcinoma (PTC) cells obtained via CNB remains unclear. Hence, we examined the differences between the PTC nuclear features in CNB and thyroidectomy specimens.

Concepts: Cancer, Biopsy, Pathology, Thyroid disease, Needle aspiration biopsy, Thyroidectomy, Thyroid neoplasm


Signet ring cell carcinoma (SRCC) is unique rare subtype of mucin-producing colorectal adenocarcinoma characterized by presence of signet ring cells, in >50% of the tumor tissue. This study aims to investigate expression of EGFR, E-cadherin and MMP-13 expression on clinicopathological features of signet ring cell type and its prognostic effect using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal cancer cases among which 19 cases of SRCC. High density manual tissue microarrays were constructed using modified mechanical pencil tips technique and immunohistochemistry for EGFR, E-cadherin and MMP-13 expression was done. We found that SRCC was significantly associated with younger age and more frequency of LN metastasis than all other groups. SRCC was also significantly associated with annular gross picture, more depth of invasion, advanced stage, more lymphovascular emboli, more perineural invasion and less arousal from an overlying adenoma. In conclusion, colorectal SRCC has distinctive clinicopathological and histological features with different unique mechanisms of carcinogenesis and more aggressive biologic behavior than other colorectal carcinoma subtypes. Negative/low expressions of EGFR and E-cadherin and MMP-13 were found in SRCC with no effect on the prognosis.

Concepts: Cancer, Lung cancer, Anatomical pathology, Histology, Colorectal cancer, Adenocarcinoma, DNA microarray, Signet ring cell carcinoma