Kristine M. Cornejo

Renal Cell Carcinoma in Tuberous Sclerosis Complex

Renal cell carcinoma (RCC) occurs in 2% to 4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathologic, and molecular features, enabling separation of these 46 tumors into 3 groups. The largest subset of tumors (n=24) had a distinct morphologic, immunologic, and molecular profile, including prominent papillary architecture and uniformly deficient succinate dehydrogenase subunit B (SDHB) expression prompting the novel term “TSC-associated papillary RCC (PRCC).” The second group (n=15) were morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT), whereas the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated PRCCs had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCCs showed strong, diffuse labeling for carbonic anhydrase IX (100%), CK7 (94%), vimentin (88%), and CD10 (83%) and were uniformly negative for SDHB, TFE3, and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes, which may help to expand the morphologic spectrum of TSC-associated RCC.

Oncofetal protein IMP3, a new diagnostic biomarker to distinguish malignant mesothelioma from reactive mesothelial proliferation.

The distinction of malignant mesothelioma from reactive mesothelial proliferation remains to be a major challenge for surgical pathologists. In this study, we investigated whether insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3), an oncofetal protein, can be used as a biomarker to distinguish between malignant and reactive mesothelial cells. A total of 109 cases (mesothelioma, n=45; reactive mesothelial proliferation, n=64) were examined by immunohistochemistry for IMP3 expression. IMP3 showed strong cytoplasmic staining in 33 of 45 (73%) mesothelioma cases. In contrast, the expression of IMP3 was undetectable in all (64 cases) benign reactive mesothelial proliferations. Among the IMP3-positive mesotheliomas, 27 (82%) exhibited diffuse IMP3 expression. The vast majority of IMP3-positive subtypes of mesotheliomas showed IMP3 expression in >50% of malignant cells, as this diffuse staining pattern occurred in 17 (81%) cases of epithelial, 4 (100%) cases of sarcomatoid, and 6 (75%) cases of mixed types of mesothelioma. In addition, 2 cases, which were initially diagnosed as atypical mesothelial proliferations and later confirmed to be mesotheliomas, showed diffuse IMP3 expression. Our findings suggest that IMP3 is a new positive biomarker for malignant mesothelioma. IMP3 immunohistochemical staining can be used as an adjunct tool in the distinction of malignant mesothelioma from reactive mesothelial proliferations.

Oncofetal protein IMP3: a useful diagnostic biomarker for leiomyosarcoma

An accurate diagnosis between leiomyoma and leiomyosarcoma is essential for patient management. IMP3 is a member of the insulin-like growth factor (IGF-II) mRNA binding protein (IMP) family that consist of IMP1, IMP2, and IMP3. IMP3 is an oncofetal protein associated with aggressive and advanced tumors and is specifically expressed in malignant tumors but not found in benign tissues. The aim of this study was to determine the expression and diagnostic value of IMP3 in leiomyoma and leiomyosarcoma. A total of 216 cases (resection, n = 183; biopsy, n = 33) consisting of 82 leiomyosarcomas (uterine, n = 15; soft tissue, n = 67), 62 leiomyomas (uterine, n = 50; soft tissue, n = 12), and 72 uterine-variant leiomyomas (atypical, n = 19 [14%]; cellular, n = 21 [16%]; mitotically active, n = 12 [9%]; myxoid, n = 11 [8%]; vascular, n = 3 [2%]; epithelioid, n = 1 [1%]; benign metastasizing, n = 1 [1%]; and smooth muscle tumors of uncertain malignant potential, n = 4) were examined by immunohistochemistry for IMP3 expression. IMP3 showed strong cytoplasmic staining in 43 (52%) of 82 leiomyosarcomas, regardless of histologic grades. There was no difference in IMP3 expression between uterine and soft tissue leiomyosarcomas. In contrast to malignant tumors, IMP3 expression was not found in any of the typical leiomyomas (0/62 cases). All uterine-variant leiomyomas were negative, except for 3 cases (atypical variant, n = 2; cellular variant, n = 1) for IMP3 staining. In summary, we are the first to describe IMP3 expression in smooth muscle tumors. Our findings indicate that the expression of IMP3 in both uterine and soft tissue leiomyosarcomas can be used as a positive biomarker to increase the level of confidence in establishing a definitive diagnosis of a malignant smooth muscle tumor.

Metastatic Carcinoma to the Thyroid Gland: A Single Institution 20-Year Experience and Review of the Literature

The thyroid gland is an uncommon site for metastatic disease but cases have been well-documented in the literature, particularly in autopsy series. A retrospective review of surgical pathology and autopsy pathology database for patients with metastatic carcinoma to the thyroid was performed at the University of Massachusetts Medical Center between January 1993 to January 2013. We identified a total of 10 patients with metastatic carcinoma to the thyroid; 6 were in surgical pathology specimens out of a total of 1,295 thyroid carcinoma (0.46xa0%) and 4 were diagnosed at autopsy out of a total of 2,117 (0.19xa0%) autopsy cases during this period. Cases with direct extension of the tumor into the thyroid from local primary sites such as larynx, esophagus or soft tissues of the neck were excluded. The primary tumors in these cases comprised of four lung carcinomas, three colorectal carcinomas, a renal cell carcinoma, a pleural malignant mesothelioma, and an unknown primary. Therefore, it is important to keep intrathyroidal metastases in the differential diagnosis when evaluating a thyroid nodule, particularly in patients with a previous history of malignancy. Furthermore, a literature review reveals over 1,400 cases have been previously reported, with the most common malignancies from the kidney (34xa0%), lung (15xa0%), gastrointestinal tract (14xa0%), and breast (14xa0%).

Pilomatrix carcinoma: a case report and review of the literature.

Pilomatrixoma is a common benign neoplasm of children and young adults with a female predilection. In contrast, its malignant counterpart, pilomatrix carcinoma is a rare neoplasm of older adults with a male preponderance. Pilomatrix carcinomas are locally aggressive with a tendency to recur. We report a case of a 44-year-old male who presented with an enlarging soft tissue tumor on the right upper back. Histology revealed an asymmetric, poorly circumscribed, lobulated neoplasm located deeply in the dermis with infiltration into the underlying subcutaneous tissue. The tumor was comprised of basaloid cells containing vesicular nuclei, prominent nucleoli, scant cytoplasm, and brisk mitotic activity. A focus of basaloid cells transitioning to shadow cells with central keratinized material and tumor necrosis was also present. The diagnosis of a pilomatrix carcinoma was rendered. Considering the infiltrative nature of this neoplasm with perineural and intramuscular invasion, the patient underwent 3 surgical excisions before it was completely removed.

Theranostic and molecular classification of breast cancer.

CONTEXTnDespite advances in breast cancer management, women continue to relapse and die of breast cancer. Traditionally, evaluation for hormone receptors (estrogen and progesterone), as well as HER2 overexpression, have guided therapy-related decision-making because they are both prognostic and predictive indicators. However, there are limitations with those studies, which can lead to improper treatment. Gene signatures have recently been shown to be of value in identifying molecular portraits of breast carcinoma and are beginning to play role in management and treatment algorithms.nnnOBJECTIVEnTo provide a summary of the prognostic and predictive indicators of breast cancer, such as hormone receptors, HER2, and molecular gene signatures that currently help guide clinical decision making.nnnDATA SOURCESnPublished articles from peer-reviewed journals in PubMed (US National Library of Medicine).nnnCONCLUSIONSnEmerging evidence shows promise that, in addition to hormone receptors and HER2 studies, evaluating tumors with gene expression profiling can provide additional prognostic and predictive information, further aiding clinical management and leading to a more personalized approach to treating breast cancer.

The utility of MYC and FLT4 in the diagnosis and treatment of postradiation atypical vascular lesion and angiosarcoma of the breast

Atypical vascular lesions (AVLs) and angiosarcomas (ASs) are well-recognized complications of radiotherapy for breast cancer. Early diagnosis may be challenging, particularly on small biopsies, and the treatment options are limited. Recently, MYC and sometimes FLT4 gene amplification has been reported in AS, but not in AVL, and FLT4 may be a target for therapy. We evaluated the MYC/FLT4 status in AVL and AS by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), determined its utility in differentiating these 2 entities in small biopsies, and ascertained the value of FLT4 as a potential marker for targeted therapy. Thirty-five vascular neoplasms were reviewed from 21 breast cancer patients who received radiotherapy (AVL, n = 18; AS, n = 17). MYC expression by IHC and/or gene amplification by FISH were identified in 13 (77%) of 17 ASs, but none of the AVL cases. Four patients had biopsies with follow-up excisions, of which 1 showed the morphology of an AVL on biopsy and AS on excision, both positive for MYC. Of 17 ASs, 3 (18%) showed strong and diffuse 3+ cytoplasmic FLT4 staining by IHC and FLT4 gene amplification by FISH. All 3 cases were coamplified for the MYC gene. Focal and weak FLT4 cytoplasmic immunoreactivity was present in 2 (12%) of 17 AVL cases and 12 (70%) of 17 AS cases. Although MYC is a valuable ancillary tool in distinguishing AS from AVL, FLT4 IHC may be used to screen for patients with FLT4 gene amplification who might benefit from targeted therapy, as only diffuse strong FLT4 immunoreactivity correlated with FLT4 gene amplification.

Malignant melanoma within squamous cell carcinoma and basal cell carcinoma: is it a combined or collision tumor?--a case report and review of the literature.

AbstractWe report a case of a very unusual combined and collision basosquamous melanocytic malignant tumor on the chest of an 84-year-old man. To our knowledge, this is the first case report describing this entity. We attempt to address the diagnostic challenge and the clinical and histological characteristics of these rare neoplasms with a review of the English literature to further categorize and summarize what has been previously reported about these extraordinary tumors.

A cutaneous interstitial granulomatous dermatitis-like eruption arising in myelodysplasia with leukemic progression

Cutaneous manifestations associated with myelodysplastic syndromes (MDS) are uncommon and can occur as specific or nonspecific lesions. Recognizing these cutaneous manifestations is important as they can precede blood or bone marrow transformation to leukemia. Granulomatous reactions have rarely been described as nonspecific lesions of MDS. These rare cases histologically resembled granuloma annulare, sarcoid, and a generalized dermal interstitial granulomatous dermatitis (IGD) which were not associated with leukemic infiltration. The authors report an interesting case of an IGD-like eruption evolving over the course of MDS with eventual progression to systemic leukemia. IGD is an inflammatory reaction that refers to a varied spectrum of histologic patterns and is associated with a variety of systemic illnesses and hypersensitivity reactions, including lymphoma and leukemia. In patients with MDS, surveillance for leukemia is a critical component of their follow-up care. Normally, this surveillance occurs through serial peripheral blood smears and bone marrow studies. IGD-like eruptions are a cutaneous reaction pattern that may serve as an additional clinical indicator of leukemic progression in patients with MDS. Although primarily a reactive pattern, this entity can rarely harbor leukemic blasts.

Preoperative Neutrophil-to-Lymphocyte Ratio and Neutrophilia Are Independent Predictors of Recurrence in Patients with Localized Papillary Renal Cell Carcinoma

Objective. To evaluate the role of preoperative neutrophil-to-lymphocyte ratio (NLR) and absolute neutrophil count (ANC) in patients prognosis with localized papillary renal cell carcinoma (pRCC). Methods. Data from 218 localized pRCC patients (T1-3 N0/+ M0), operated between 1991 and 2011 at two centers, were evaluated retrospectively. Univariable and multivariable analyses using the Cox regression model were performed to determine the associations of NLR and ANC with recurrence-free survival (RFS). Prognostic accuracy was evaluated with the Harrell concordance index. Results. The 5-year RFS rate was 87.0%. Multivariable analysis identified increased NLR (≥3.6) and ANC (≥5300/μL) as independent prognostic factors for RFS (hazard ratio (HR) = 4.01, P = 0.018) and (HR = 4.71, P = 0.045). The final model built by the addition of NLR or ANC improved predictive accuracy (c-index: 0.824, 0.842) compared with the clinicopathological base model (c-index: 0.800), which included TNM stage and tumor necrosis. Conclusions. The NLR and ANC appear to be independent prognostic factors for RFS after surgery for localized pRCC. They significantly increase the accuracy of established prognostic factors. Therefore, we recommend adding NLR and ANC to traditional prognostic model, which may improve its predictive accuracy.