Monalisa Sur

TdT expression in Merkel cell carcinoma: potential diagnostic pitfall with blastic hematological malignancies and expanded immunohistochemical analysis.

Merkel cell carcinoma is an uncommon aggressive primary cutaneous neuroendocrine carcinoma. Histologically, the differential diagnosis includes the ‘small round cell’ tumor group, particularly metastatic small cell carcinoma and blastic hematological malignancies involving skin/soft tissues. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase, which is a sensitive and specific antibody for acute lymphoblastic lymphoma with a small proportion of acute myeloid leukemia showing positivity. This study investigates the expression of TdT in 20 cases with initial diagnosis of Merkel cell carcinoma. Archival blocks and slides were retrieved and reviewed and clinical information obtained from patient charts. Immunohistochemistry was performed and graded as: 0, no staining; 1+, less than 50% staining in the cells; 2+, 50% or more staining in the cells. After review, 15 cases were confirmed as Merkel cell carcinoma. Immunohistochemical positivity was as follows: 8/15 cases were positive for TdT with strong nuclear staining, morphologically resembling ‘blasts’, AE1AE3, CAM5.2 (15/15) (both membrane and paranuclear dot positivity), CD56 and BCL-2 (15/15), Synaptophysin (13/15), Chromogranin A (11/15), NSE (15/15), CK20 (14/15), CK7 (3/15), both CK7 and CK20 (3/15), CD117 (8/15), CD99 (2/15), CD10 (1/15). One case was negative for CK7/CK20. All 15 cases were negative for thyroid transcription factor-1, LCA, CD20, CD3 and CD34. Expanded immunohistochemical panel with positive staining for epithelial/neuroendocrine markers, CK20, negative staining for hematolymphoid markers and awareness of TdT expression and other markers that show overlap with blastic hematological malignancies avoids misinterpretation in the diagnosis of Merkel cell carcinoma. This aids in further diagnosis of Merkel cell carcinoma, avoiding the potential diagnostic pitfall with other small round cell tumors and hematological malignancies primary or metastatic to the skin.

Frequency of serous tubal intraepithelial carcinoma in various gynecologic malignancies: a study of 300 consecutive cases.

Serous tubal intraepithelial carcinoma (STIC) has been implicated in the pathogenesis of pelvic serous carcinoma. We hypothesized that, if this is the case, the frequency of STIC should be substantially lower in endometrial serous carcinomas, in nonserous gynecologic malignancies, and in benign gynecologic neoplasms than in ovarian or peritoneal serous carcinomas. From 2007 to 2009 the fallopian tubes of 342 consecutive gynecologic cases were entirely submitted for histology using the Sectioning and Extensively Examining the FIMbriated end protocol. This study included 300 of these cases (277 TAH-BSO, 23 BSO) after exclusion. The hematoxylin and eosin-stained slides from the fallopian tubes were independently reviewed by 2 gynecologic pathologists who were blinded to all other findings; disagreements were resolved by a third pathologist. Among 46 cases of ovarian malignancies, STIC was identified in 6 (18.8%) of 32 cases of serous carcinoma, but not in any other subtype. Similarly, STIC coexisted in 4 (14.3%) of 28 cases of endometrial serous carcinoma; however, no STIC was identified in any of the 74 cases of nonserous endometrial malignancies. STIC was identified in 2 (28.6%) of 7 cases of peritoneal serous carcinoma. No STIC was identified among 15 nongynecologic malignancies, 90 cases of benign conditions, and 27 cases of other conditions including 4 cases of cervical adenocarcinoma in situ and high-grade cervical intraepithelial lesions, 8 cases of endometrial atypical complex hyperplasias, and 15 cases of ovarian borderline tumors. In conclusion, the fallopian tube may be the origin of some pelvic serous carcinomas. Other possibilities that may explain the origin of pelvic high-grade serous carcinoma are discussed. Given that STIC coexisted with 14% of endometrial serous carcinomas, a more unifying theory may be that gynecologic serous carcinomas and STIC are multifocal lesions.

THE ROLE OF THE HUMAN PAPILLOMA VIRUS IN ESOPHAGEAL CANCER

Summary Esophageal squamous cell carcinoma (ESCC) demonstrates wide regional variation in incidence and causal associations. Human papillomavirus (HPV) has been implicated in ESCC, particularly the sub‐types 16 and 18. Transforming proteins E6 and E7 from these high risk sub‐types, interact with p53 protein and Rb protein respectively, leading to loss of function of these tumor suppressor gene products. These interactions further lead to inactivation of the growth suppressive effects of the p53 and Rb proteins, resulting in abnormal proliferative states. p53 protein expression has been found in both HPV‐positive and ‐negative tumors, indicating that HPV and p53 protein expression are not mutually exclusive and can occur together in the same tumor. It has been observed that HPV plays a more significant role in esophageal carcinogenesis in geographic areas with a high prevalence of the disease. A variation in the association between HPV and ESCC worldwide may be due to environmental and geographic factors, or to genetic susceptibility to esophageal HPV infections. Variations in the sensitivity of techniques used in the detection of the virus and in the methodology for processing the tumor tissues, may also be responsible for global differences. Esophageal carcinogenesis is a complex multistep process with a multifactorial etiology. Infection with oncogenic HPV types may be an integral part in a multistep process that leads to ESCC.Abbreviations: ESCC, esophageal squamous cell carcinoma; HPV, human papillomavirus; ISH, in situ hybridisation; SCC, squamous cell carcinoma.

Primary anaplastic large cell lymphoma of the breast arising in reconstruction mammoplasty capsule of saline filled breast implant after radical mastectomy for breast cancer: an unusual case presentation

BackgroundPrimary non-Hodgkin lymphoma (NHL) of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of the breast described in the literature. Eight of these cases occurred in proximity to breast implants, four in relation to silicone breast implant and three in relation to saline filled breast implant with three out of the eight implant related cases having previous history of breast cancer treated surgically. Adjuvant postoperative chemotherapy is given in only one case. Secondary hematological malignancies after breast cancer chemotherapy have been reported in literature. However in contrast to acute myeloid leukemia (AML), the association between lymphoma and administration of chemotherapy has never been clearly demonstrated.Case PresentationIn this report we present a case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of saline filled breast implant after radical mastectomy for infiltrating ductal carcinoma followed by postoperative chemotherapy twelve years ago.ConclusionPrimary ALK negative ALCL arising at the site of saline filled breast implant is rare. It is still unclear whether chemotherapy and breast implantation increases risk of secondary hematological malignancies significantly. However, it is important to be aware of these complications and need for careful pathologic examination of tissue removed for implant related complications to make the correct diagnosis for further patient management and treatment. It is important to be aware of this entity at this site as it can be easily misdiagnosed on histologic grounds and to exclude sarcomatoid carcinoma, malignant melanoma and pleomorphic sarcoma by an appropriate panel of immunostains to arrive at the correct diagnosis of ALCL.

Cytoskeletal myotoxicity from simvastatin and colchicine.

We report the case of a 79‐year‐old man with mild chronic renal failure who developed severe rhabdomyolysis after combined exposure to simvastatin and colchicine. Colchicine induces myopathy through disruption of microtubular function with subsequent vacuolization and pseudomyelinic body accumulation. Statin therapy is associated with myonecrosis, membranous myeloid bodies, and vacuolization, presumably as a function of impaired isoprenoid metabolism. Vesicle trafficking requires small G‐protein prenylation and statins can disrupt cytoskeletal integrity. We propose that synergistic cytoskeletal myotoxicity may account for the extreme elevation of serum creatine kinase not previously reported in pure colchicine myopathy. Muscle Nerve, 2004

Morphologic alterations in esophageal squamous cell carcinoma after preoperative high dose rate intraluminal brachytherapy.

Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (Gy) in 2 fractions of 10 Gy each week were reviewed for radiation changes.

Investigation of human papillomavirus in transitional cell carcinomas of the urinary bladder in South Africa

Aim: To investigate the prevalence of human papillomavirus in transitional cell carcinoma of the urinary bladder in South Africa. Methods: Ninety‐one archival samples of bladder transitional cell carcinoma were subjected to polymerase chain reaction (PCR) and non‐isotopic in situ hybridisation (NISH) for the detection of human papillomavirus 6, 11, 16, 18, 31, and 33 genotypes. Results: HPV was detected in only one case with PCR. HPV was not detected in any of the cases subjected to the NISH system. Conclusion: This study shows that although HPV has been shown to be associated with uterine cervical and esophageal squamous cell carcinomas in South Africa, this virus is not present in the transitional cell carcinoma of the urinary bladder in this geographical location. It is suggested that other factors, including nitrosamine exposure, p53 mutation, and additional unknown chromosomal events, may play a role in the carcinogenesis of this neoplasm in the bladder.

Do deeper sections increase the frequency of detection of serous tubal intraepithelial carcinoma (STIC) in the "sectioning and extensively examining the FIMbriated end" (SEE-FIM) protocol?

Studies have suggested serous tubal intraepithelial carcinoma (STIC) of the fallopian tube to be a putative precursor to ovarian and peritoneal serous carcinoma. It has been recommended that resected fallopian tube specimens should be rigorously examined for STIC, especially in women at high risk of serous carcinoma, such as those with BRCA mutations or with a strong family history. The SEE-FIM protocol allows for the greatest surface area of the tube to be histologically assessed. There have been suggestions that multiple deeper sections should be examined if the initial hematoxylin and eosin (H&E) sections are negative; however, whether this identifies more cases of STIC has not rigorously examined. We examined deeper sections from 56 cases of pelvic carcinoma in which the initial H&E sections of the fallopian tubes were negative for STIC. All initial and deeper sections underwent consensus review by panel of experts in gynecologic pathology. These cases are part of a larger study in which we had examined 300 consecutive bilateral salpingectomies using the SEE-FIM protocol and a single-H&E section per block and had identified 68 cases of pelvic serous carcinoma, of which 12 were associated with STIC. We calculated the sensitivity of a single-H&E section to detect STIC, as compared with examination of multiple deeper sections, and reevaluated the clinicopathologic data of the parent study in light of the additional cases of STIC. In the 56 cases initially negative for STIC, 4 cases of STIC were identified after examination of multiple deeper sections of the fallopian tubes. The single-H&E section SEE-FIM approach therefore detected only 75% (95% confidence interval, 51%–90%) of STIC that was present. Three of these new cases were associated with primary ovarian serous carcinoma and 1 with primary peritoneal serous carcinoma. All 3 new cases associated with ovarian carcinoma were noted in women without neoadjuvant chemotherapy. In considering the data from the parent study, we calculated a statistically significant lower incidence of STIC in women with ovarian serous carcinoma who received neoadjuvant chemotherapy as compared with those who did not (P=0.042). Our study demonstrated that additional cases of STIC can be detected if deeper sections are examined. These additional cases also highlighted a statistically significant difference in the incidence of STIC associated with ovarian serous carcinoma who received neoadjuvant chemotherapy relative to those who did not. Consideration to this should be given in future studies of the prevalence of STIC and to routine examination of salpingectomy specimens from women at high risk for pelvic serous carcinoma.

Agranular CD4+/CD56+ hematodermic neoplasm : A distinct entity described in the recent world health organization-european organization for research and treatment of cancer classification for cutaneous lymphomas

Agranular CD4+/CD56+ hematodermic neoplasm is a distinct form of lymphoma with aggressive behavior and marked predilection for cutaneous involvement. Because of CD56 positivity, natural killer cells were initially suggested as the cell of origin in this tumor. In the recent World Health Organization-European Organization for Research and Treatment of Cancer classification, the term blastic natural killer cell lymphoma has been replaced with CD4+/CD56+ hematodermic neoplasm because of its derivation from a plasmacytoid dendritic cell precursor. Clinicopathologic features, immunohistochemical features, and differential diagnosis of this rare neoplasm with emphasis on the recent World Health Organization-European Organization for Research and Treatment of Cancer classification are discussed.

Synchronously diagnosed lymph nodal collision tumor of malignant melanoma and chonic lymphocytic leukemia/small lymphocytic lymphoma: case report

Synchronous composite tumors have been described but are uncommon. Moreover, simultaneous occurrence of synchronous tumors in the same tissue or organ is even less common. We report a case of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma and malignant melanoma (MM) occurring synchronously in the same lymph node. Several cases of an association between cutaneous malignancies and lymphoproliferative disorders have been reported. Some of which included CLL and MM, occurring in the same patient often CLL after MM. The risk of having CLL after MM has been reported to be increased. Various genetic and environmental etiologies have been postulated, but have as yet not been proven. To our knowledge this is the first time that synchronous occurrence of these two malignant processes in the same tissue is described. In this case it is important that the melanoma was recognized in the excised lymph node, as this finding had much more critical treatment and long term survival consequences.