25 research outputs found
Juvenile Granulosa Cell Tumors of the Testis: A Clinicopathologic Study of 70 Cases with Emphasis on Its Wide Morphologic Spectrum
The clinical and pathologic features of 70 juvenile granulosa cell tumors (JGCTs) of the testis are presented. The patients were from 30 weeks gestational age to 10 years old; 60 of 67 (90%) whose ages are known to us were 6 months old or younger. Sixty-two underwent gonadectomy, 6 wedge excision, and 2 only biopsy. Twenty-six tumors were left sided and 22 right sided. Six occurred in an undescended testis and 2 in dysgenetic gonads. The most common presentation was a testicular mass (65%), followed by an “enlarging testis” (25%). Six of 14 patients in whom it was measured had “elevated” serum α-fetoprotein (AFP), likely physiologically, and 1 had gynecomastia. The tumors measured 0.5 to 5 cm (mean, 1.7 cm; median, 1.5 cm) and were most commonly well circumscribed and typically yellow-tan; approximately 2/3 had a cystic component, whereas 1/3 were entirely solid. Microscopic examination typically showed a lobular growth, punctuated in 67 cases by variably sized and shaped follicles containing material that was basophilic (21%), eosinophilic (44%), or of both characters (35%); 3 lacked follicles. In nonfollicular areas, the tumor cells typically grew diffusely but occasionally had a corded arrangement (26%) or reticular appearance (29%). The stroma was either fibrous or fibromyxoid; hemorrhage associated with hemosiderin-laden macrophages was focally seen in 16%. The tumor cells were mostly small to medium sized with round to oval nuclei containing inconspicuous nucleoli and moderate to abundant, but occasionally scant, pale to lightly eosinophilic, sometimes vacuolated, cytoplasm; nuclear grooves were infrequent (6%). Focal columnar morphology was seen in 27% of the tumors. Mitoses were plentiful in 37%, and apoptosis was prominent in 46%. Intratubular tumor was seen in 43% and entrapped seminiferous tubules in 70%. Lymphovascular invasion was present in 2 cases, rete testis involvement in 4, and necrosis in 1. Rare features/patterns included: regressed tumor with hyalinization and prominent blood vessels (13%), papillary growth (4%), basaloid morphology (1%), spindle cell predominance (1%), microcystic foci (1%), adult granulosa cell–like (1%) patterns, and hyaline globules (1%). Inhibin (16/18), calretinin (8/9), WT1 (6/7), FOXL2 (12/12), SF-1 (12/12), and SOX9 (6/11) were positive, whereas SALL4 and glypican-3 were consistently negative in the neoplastic granulosa cells. Only 1 of 10 tumors was focally positive for α-fetoprotein. JGCT is a rare neoplasm with a wide morphologic spectrum that also occurs rarely in undescended testes and dysgenetic gonads. The solid and reticular patterns may pose diagnostic challenges, but the lobular appearance and follicular differentiation are characteristic. Immunohistochemical stains may aid in its distinction from other tumors of young male individuals, particularly yolk sac tumor, a neoplasm that peaks at a somewhat later age. Twenty-four patients with follow-up, including 4 of 6 patients treated with wedge resection/biopsy, had no evidence of disease (2 to 348 mo; mean, 83 mo; median, 61 mo). One additional patient was alive at 260 months, but the disease status is unknown. The benign clinical course of all cases of JGCT with follow-up, despite often frequent mitotic activity, supports testis sparing surgery when technically feasible
Widespread presentation and spontaneous regression of porokeratotic eccrine ostial and dermal duct nevus
Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is an uncommon hamartomatous growth with disordered keratinization. The lesions typically appear on the limbs, often at birth or in early childhood, as linearly distributed papules and plaques. We report 4 cases of PEODDN, 2 of which showed significant spontaneous regression
Next-Generation Sequencing to Detect Deletion of RB1 and ERBB4 Genes in Chromophobe Renal Cell Carcinoma: A Potential Role in Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma
Overlapping morphologic, immunohistochemical, and ultrastructural features make it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Because ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to identify genetic markers that distinguish ChRCC from RO by using next-generation sequencing (NGS). NGS for hotspot mutations or gene copy number changes was performed on 12 renal neoplasms, including seven ChRCC and five RO cases. Matched normal tissues from the same patients were used to exclude germline variants. Rare hotspot mutations were found in cancer-critical genes (TP53 and PIK3CA) in ChRCC but not RO. The NGS gene copy number analysis revealed multiple abnormalities. The two most common deletions were tumor-suppressor genes RB1 and ERBB4 in ChRCC but not RO. Fluorescence in situ hybridization was performed on 65 cases (ChRCC, n = 33; RO, n = 32) to verify hemizygous deletion of RB1 (17/33, 52%) or ERBB4 (11/33, 33%) in ChRCC, but not in RO (0/32, 0%). In total, ChRCCs (23/33, 70%) carry either a hemizygous deletion of RB1 or ERBB4. The combined use of RB1 and ERBB4 fluorescence in situ hybridization to detect deletion of these genes may offer a highly sensitive and specific assay to distinguish ChRCC from RO
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
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
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
We 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
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 (0.46 %) and 4 were diagnosed at autopsy out of a total of 2,117 (0.19 %) 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 (34 %), lung (15 %), gastrointestinal tract (14 %), and breast (14 %)
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
Renal Cell Carcinoma in Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which renal manifestations are prominent. There are three major renal lesions in TSC: angiomyolipomas, cysts, and renal cell carcinoma (RCC). Major recent advances have revolutionized our understanding of TSC-associated RCC, including two series that together include more than 100 TSC-RCC cases, demonstrating a mean age at onset of about 36 years, tumors in children as young as 7, and a striking 2:1 female predominance. These series also provide the first detailed understanding of the pathologic features of these distinctive tumors, which include chromophobe-like features and eosinophilia, with some of the tumors unclassified. This pathologic heterogeneity is distinctive and reminiscent of the pathologic heterogeneity in Birt–Hogg–Dube-associated RCC, which also includes chromophobe-like tumors. Additional advances include the identification of sporadic counterpart tumors that carry somatic TSC1/TSC2/mTOR mutations. These include unclassified eosinophilic tumors, eosinophilic solid cystic RCC (ESC-RCC), and RCC with leiomyomatous stroma (RCCLMS). A variety of epithelial renal neoplasms have been identified both in patients with tuberous sclerosis complex (TSC) and in the nonsyndromic setting associated with somatic mutations in the TSC1 and TSC2 genes. Interestingly, whether tumors are related to a germline or somatic TSC1/2 mutation, these tumors often display similar morphologic and immunophenotypic features. Finally, recent work has identified molecular links between TSC and BHD-associated tumors, involving the TFEB/TFE3 transcription factors
Syringofibroadenoma arising adjacent to verrucous carcinoma: Is it a reactive process, malignant transformation, or collision tumor?
Eccrine syringofibroadenoma (ESFA) is a rare, benign tumor showing acrosyringeal or sweat gland differentiation with variable clinical presentations, but distinct histopathological features. Rarely, ESFA coexists with a malignancy such as a squamous cell carcinoma or porocarcinoma. Herein, we report the first case of an ESFA associated with a verrucous carcinoma in a 46-year-old female on the right foot. It is unclear whether it represents a reactive process, a malignant transformation or a collision tumor. We recommend ESFA be completely excised if possible or closely followed given its association with a developing carcinoma