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.
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.
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.
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.
Hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma (HLRCC)/fumarate hydratase deficient renal cell carcinoma (FHRCC) is defined by molecular genetic changes (mutation/LOH in fumarate hydratase (FH) gene). We investigated chromosomal numerical aberration pattern (CNV) in FHRCC/HLRCC using array comparative genomic hybridization analysis and low pass whole genome sequencing. Genetic analysis was successfully completed in 12 tumors. Most common chromosomal aberrations detected were a complete or partial loss of chromosome 4 (5/12 cases), chromosome 15 (4/12 cases), and chromosomes 9, 13, and 14 (each in 3/12 cases), as well as a complete or partial gain of chromosome 17 (in 4/12 cases). No chromosomal losses or gains were detected in 4 cases. Copy number variation pattern in FHRCC/HLRCC appears to be highly variable and does not provide a useful diagnostic tool in identifying these cases. Immunohistochemical staining and especially molecular genetic evaluation of FH gene mutations/LOH remain the gold standard in identifying FHRCC/HLRCC.
Prostatic ductal adenocarcinoma (PDA) is a rare histologic subtype of prostate cancer characterized by large glands lined with tall columnar pseudostratified epithelium. PDA has several architectural patterns, with papillary and cribriform being the most common. The cribriform pattern of acinar carcinoma has shown to be associated with a worse prognosis in terms of disease progression and disease-specific mortality. However, the significance of cribriform pattern in PDA is unknown. In this study, we sought to compare the adverse pathologic features between cribriform-type and non-cribriform-type PDA, and between PDA and acinar carcinoma with Gleason scores 8-10. We identified PDA cases diagnosed between 2008 and 2018 and 428 radical prostatectomy (RP) specimens containing Gleason 8-10 acinar carcinoma. The slides of all PDA cases were reviewed, and pathologic features were recorded. We found that the vast majority of PDA contained admixed acinar carcinoma, with a median percentage of the ductal component of 50% (range 5-100). 29% of PDA was graded as Grade Group 4 and 35.5% as Grade Group 5. At the time of RP, 45.2% of cases presented as pathologic stage T3a and 29% as T3b. Cribriform-type PDA demonstrated a significantly higher likelihood of extraprostatic extension (84% vs 33.3%, p = 0.01), seminal vesical invasion (36% vs 0%, p = 0.04), lymphovascular invasion (40% vs 0%, p = 0.03) and advanced pathologic stage (84% vs 33.3%, p = 0.01) compared to PDA without cribriform architecture. The proportion of stage ≥pT3 tumors in PDA was similar compared to that in Gleason 8-10 acinar carcinoma (74.2% vs 70.8%, p = 0.68).
The transmembrane receptor NOTCH1 is thought to be associated with the development and progression of T-acute lymphoblastic leukemia (T-ALL)/T-lymphoblastic lymphoma (T-LBL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The current study aimed to characterize NOTCH1 expression and elucidate the variants in the functional PEST domain of the receptor in T-ALL/LBL and CLL/SLL. The nuclear expression of NOTCH1 protein was detected in 25% and 5% of cases of T-ALL/LBL and CLL/SLL, respectively, whereas cytoplasmic expression was detected in 33.3% and 15% cases, respectively. The frequency of variants in T-ALL/LBL was 33%, whereas 40% of CLL/SLL cases possessed variants. Four novel variants were identified; three of which were non-synonymous and one common variant c.7280_7280delG between T-ALL/LBL and CLL/SLL cases. The previously described variant, c.7541_7542delCT, was detected in 3 cases of CLL/SLL. These results provide support for the contribution of NOTCH1 in the etiology of these types of cancers.
Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease which has an unpredictable risk of progression to muscle-invasive bladder cancer (MIBC). The selection of patients who may benefit from early radical intervention is a challenge. To define the useful prognostic markers for progression, we analyzed the immunohistochemical expression of fatty acid synthase (FASN), Her2/neu, and E2F1 in 60 cases of NMIBC who underwent TURBT and adjuvant intravesical bacillus-Calmette-Guérin (BCG). Their predicting role for tumor recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS) was analyzed. High FASN expression was observed in 56.7% (34/60) of NMIBC cases, and FASN expression was significantly associated with the tumor size, grade, and tumor stage (p = 0.003, p < 0.001, p < 0.0001 respectively). Positive Her2/neu was noted in 18.3% (11/60) of the cases, and its expression was significantly associated with the tumor size, histologic grade, and tumor stage (p = 0.001, p = 0.002, p = 0.011 respectively). High E2F1 expression was detected in 40% of the cases, and it was associated with tumor size, histologic grade, and tumor stage (p < 0.001 for each). Analysis of follow-up period revealed that NMIBC with high FASN, positive Her2/neu, and high E2F1 expression exhibited a potent relation with tumor progression, shorter RFS, and poor PFS. Conclusions: High FASN, Her2/neu, and E2F1 are considered as adverse prognostic factors of tumor recurrence and progression in NMIBC and these patients should be followed carefully. Therefore, we suggest that FASN, Her2/neu, and E2F1 should be considered and evaluated during the selection of the appropriate management strategy for NMIBC patients.
Breast impalpable lesions have become a clinical dilemma because they are small, presenting a heterogeneous cellular phenotype. The aim of this study was to evaluate the mutational profile of the PIK3CA, TP53, and CDKN2A genes, comparing the mammary tissue with the respective circulating free DNA (cfDNA). The PIK3CA, TP53, and CDKN2A genes were sequenced (PCR-Sanger) in 58 women with impalpable lesions (49 malignant and 9 benign) with the respective cfDNA. The chi-square or Fisher’s exact test was used to evaluate statistical significance between the clinical variables and mutational profile. A total of 51 out of 58 samples generated successful mutation profiles in both breast lesion and cfDNA. Of the 37 mutations detected, 10 (27%) and 16 (43%) mutations were detected in benign and malignant breast lesions, respectively, while 2 (5%) and 9 (24%) were found in cfDNA of women with benign and malignant lesions, respectively. The lymph node involvement with mutations in the PIK3CA in malignant lesions (P = 0.001), and the relationship between mutations in PIK3CA, comparing ductal tumors with benign lesions (P = 0.05), were statistically significant. This study detected different mutations in PIK3CA, TP53, and CDKN2A genes, which represent, in part, the heterogeneity of impalpable lesions. The results confirm that more studies should be conducted on the functional role of cfDNA in the impalpable lesions.
There is contradictory evidence in literature with respect to diagnosis and management of follicular lesions of the thyroid gland. From surgical pathology stand point, pathologists require submission and processing of entire capsule for microscopic evaluation. This can be extremely challenging especially in larger lesions.