Case of recurrent superficial CD34-positive fibroblastic tumor.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare superficial mesenchymal tumor. SCPFT has a distinctive morphologic appearance, marked by significant nuclear pleomorphism, low mitotic rate, and diffuse CD34 positivity. SCPFT is underdiagnosed because of its rarity and misdiagnosis as sarcoma, with very few reported cases of local recurrence or metastasis. Recognition and awareness of SCPFT are essential for accurate diagnosis and appropriate clinical management. We describe here the case of a 37-year-old male who presented with a right calf mass diagnosed as SCPFT with subsequent local recurrence of the tumor.

Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer.

The transformation of prostatic epithelial cells to prostate cancer (PCa) has been characterized as a transition from citrate secretion to citrate oxidation, from which one would anticipate enhanced mitochondrial complex I (CI) respiratory flux. Molecular mechanisms for this transformation are attributed to declining mitochondrial zinc concentrations. The unique metabolic properties of PCa cells have become a hot research area. Several publications have provided indirect evidence based on investigations using pre-clinical models, established cell lines, and fixed or frozen tissue bank samples. However, confirmatory respiratory analysis on fresh human tissue has been hampered by multiple difficulties. Thus, few mitochondrial respiratory assessments of freshly procured human PCa tissue have been published on this question. Our objective is to document relative mitochondrial CI and complex II (CII) convergent electron flow to the Q-junction and to identify electron transport system (ETS) alterations in fresh PCa tissue. The results document a CII succinate: quinone oxidoreductase (SQR) dominant succinate oxidative flux model in the fresh non-malignant prostate tissue, which is enhanced in malignant tissue. CI NADH: ubiquinone oxidoreductase activity is impaired rather than predominant in high-grade malignant fresh prostate tissue. Given these novel findings, succinate and CII are promising targets for treating and preventing PCa.

Superficial CD34-positive fibroblastic tumor (SCPFT): A review of pathological and clinical features.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare mesenchymal tumor of borderline malignancy. It generally involves superficial soft tissue, with a predilection to the lower extremities. Microscopically this tumor is characterized by a fascicular and storiform growth pattern, spindled to epithelioid cells, nuclear atypia with pleomorphism, and eosinophilic granular, and fibrillar to glassy cytoplasm. Strong diffuse immunoreactivity for CD34 is very characteristic of this entity. Due to under-recognition, this tumor is generally underreported. Additionally, cases of recurrence are rarely reported in the literature. We will comprehensively review the English language literature on all reported cases of SCPFT, with emphasis on recurrence.

Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features.

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

Leiomyoma of digit of hand: Report of three cases with literature review.

Leiomyoma is a benign tumor of smooth muscle origin most common in areas of the body with abundant smooth muscle including the gynecologic, genitourinary, and gastrointestinal system. Leiomyoma outside of these locations is believed to arise from vascular smooth muscle and arrector pili muscles. Leiomyoma of an extremity is a rare diagnosis, especially when present in a digit of the hand due to the paucity of smooth muscle in this location. We report three cases of leiomyoma of a digit of the hand.

Seminal vesicle invasion combined with extraprostatic extension is associated with higher frequency of biochemical recurrence and lymph node metastasis than seminal vesicle invasion alone: Proposal for further pT3 prostate cancer subclassification.

The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system subdivides prostatic pT3 tumors into pT3a, which includes cases with extraprostatic extension (EPE) and pT3b, which is defined by the presence of seminal vesicle invasion (SVI) with or without EPE. Yet, it is not established whether combined SVI and EPE impart a worse prognosis compared to SVI alone. We studied a cohort of 69 prostatectomy patients with SVI with or without EPE. Patient age at the time of radical prostatectomy was documented and Gleason score and presence or absence of EPE and/or SVI were determined. Biochemical recurrence (BCR) was defined as a PSA rise >0.2 ng/mL. The frequency of BCR was 33.9% in cases with combined EPE and SVI versus 12.5% in cases with SVI alone (relative risk = 2.71). An additional cohort of 88 patients also showed a higher frequency of lymph node metastasis of 29% in patients with combined SVI and EPE at the time of radical prostatectomy versus a 10% frequency of lymph node metastasis in patients with SVI alone (relative risk = 2.9). Based on our data, we propose further subdividing pT3 prostate cancers into three groups: EPE alone (pT3a), SVI alone (pT3b), and combined EPE and SVI (pT3c). This classification system would more accurately identify patients with pT3 prostate cancer who are more likely to experience worse outcomes and provide clinicians with additional information to aid in follow-up and postoperative treatment decisions.

Anastomosing Hemangioma of the Breast: An Unusual Case at an Unusual Site.

Anastomosing hemangioma (AH) is an unusual benign vascular lesion that commonly occurs in the kidney and genitourinary tract. We report a case of AH in a 49-year-old woman presenting as a mass in the breast, a site which, to the best of our knowledge, has not been previously documented in the English literature. Microscopic examination of the mass revealed a well-demarcated proliferation of anastomosing vascular spaces lined by bland endothelial cells, with focal hobnailing and scattered intravascular fibrin thrombi. No mitotic activity was observed and the Ki-67 proliferative index was low. These features were interpreted as AH, a lesion that may be difficult to distinguish from low-grade angiosarcoma or other benign vascular lesions of the breast which may demonstrate anastomosing channels. Due to the presence of atypical histologic features which can raise suspicion for angiosarcoma on biopsy, complete excision of these lesions is recommended for optimal treatment.

Solitary Fibrous Tumor of Breast with Anaplastic Areas (Malignant Solitary Fibrous Tumor): A Case Report with Review of Literature.

Solitary fibrous tumor (SFT) is a rare, soft tissue neoplasm that rarely presents in breast tissue, with only 27 previously reported cases. To our knowledge, only one case of malignant SFT has been reported in the English literature. A 75-year-old Caucasian woman presented to our institution with a 3-month history of a palpable left breast mass. No other symptoms, including nipple discharge or skin changes, were noted. She underwent 3 previous biopsies for right breast masses, all of which were benign, with no evidence of spindle cell neoplasm, atypical hyperplasia, or malignancy. Microscopic examination of the mass demonstrated a classic area of SFT with areas of high-grade anaplastic component. In these areas, the tumor showed atypical epithelioid cells arranged in hypercellular sheets with diminished branching vasculature, nuclear pleomorphism, and increased mitotic count (up to 9/10 high-power fields). This case represents the second case of malignant SFT in the breast.

Clear cell carcinoma of testis: A review.

Clear cell Mullerian-type adenocarcinoma of the testis is an exceedingly rare entity, and its histogenesis and clinical behavior are still poorly understood. We discuss three cases of clear cell carcinoma of the testis, compiled from a review of the literature and our personal experience. Microscopically, the tumors closely resembled clear cell carcinoma of the ovary, displaying papillae lined by clear cells with areas of hobnailing. The reported immunophenotypic features were also similar to that of ovarian tumors, as positivity for epithelial markers (CK7, CAM5.2, AE1/AE3, EMA) and Mullerian markers (PAX8, CA125) with negativity for estrogen and progesterone receptors have been observed. The pathogenesis of testicular clear cell carcinoma is still poorly understood, with reported cases displaying evidence of both mesothelial and Mullerian origin. In addition, molecular characterization of testicular clear cell carcinomas has yet to be accomplished; however, studies performed on ovarian clear cell carcinomas may provide insight to the origin, biologic behavior, and potential therapeutic modalities for this obscure, aggressive malignancy.

Clinical presentation of ductal carcinoma in situ of breast with intraluminal crystalloids: Radiologic-histologic correlation.

Intraluminal crystalloids have rarely been described in the breast, particularly in cases with ductal carcinoma in situ (DCIS). We recently encountered a case of DCIS of the breast associated with numerous intraluminal crystalloids. The patient presented with a mass in the right breast, and microcalcifications were detected on screening and diagnostic mammograms; the patient underwent needle biopsies, lumpectomy, and skin-sparing mastectomy. Invasive ductal carcinoma associated with extensive DCIS was diagnosed. Multiple refractile, eosinophilic crystalloids, with variable morphologies including rectangular, triangular and needle-like with sharp borders, were observed within the lumina of DCIS, besides calcium phosphate microcalcifications. We report this case together with a literature review on crystalloid-containing lesions in breast and non-breast tissues. We also studied radiologic findings of these crystalloids using a specimen radiograph.

Flat epithelial atypia in directional vacuum-assisted biopsy of breast microcalcifications: surgical excision may not be necessary.

The aim of this study was to analyze the clinicopathological features of patients with flat epithelial atypia, diagnosed in directional vacuum-assisted biopsy targeting microcalcifications, to identify upgrade rate to in situ ductal or invasive breast carcinoma, and determine factors predicting carcinoma in the subsequent excision. We retrospectively evaluated the histological, clinical, and mammographic features of 69 cases from 65 women, with directional vacuum-assisted biopsy-diagnosed flat epithelial atypia with or without atypical ductal hyperplasia or atypical lobular hyperplasia, which underwent subsequent surgical excision. The extent and percentage of microcalcifications sampled by directional vacuum-assisted biopsy were evaluated by mammography. All biopsy and surgical excision slides were reviewed. The age of the women ranged from 40 to 85 years (mean 57 years). All patients presented with mammographically detected microcalcifications only, except in one case that had associated architectural distortion. Extent of calcifications ranged from <1 cm (n = 47), 1-3 cm (n = 15) to > 3 cm (n = 6), and no measurement (n = 1). A mean of 11 cores (range 6-25) was obtained from each lesion. Post-biopsy mammogram revealed >90% removal of calcifications in 81% of cases. Pure flat epithelial atypia represented nearly two-thirds of directional vacuum-assisted biopsy specimens (n = 43, 62%), while flat epithelial atypia coexisted with atypical ductal hyperplasia (18 cases, 26%), or atypical lobular hyperplasia (8 cases, 12%). Upon excision, none of the cases were upgraded to in situ ductal or invasive breast cancer. In one case, however, an incidental, tubular carcinoma (4 mm) was found away from biopsy site. Excluding this case, the upgrade rate was 0%. Our study adds to the growing evidence that diagnosis of flat epithelial atypia on directional vacuum-assisted biopsy for microcalcifications as the only imaging finding is not associated with a significant upgrade to carcinoma on excision, and therefore, excision may not be necessary. Additionally, excision may not be necessary for flat epithelial atypia with atypical ductal hyperplasia limited to ≤2 terminal duct-lobular units, if at least 90% of calcifications have been removed on biopsy.

Renal collision tumor composed of oncocytoma and mucinous tubular and spindle cell carcinoma: case report of an unprecedented entity.

Primary renal collision tumors composed of 2 histologically distinct components are rare with only isolated case reports in the medical literature. Oncocytoma is a benign renal neoplasm, which is thought to originate from distal tubular epithelial cells. Mucinous tubular and spindle cell carcinoma (MTSCC) of kidney is a rare, relatively recently described renal neoplasm that was first included in the 2004 World Health Organization renal cell carcinoma (RCC) classification as a distinct entity. Current studies suggest that the tumor originates from the proximal nephron, although it is still controversial. The presence of concurrent oncocytoma with conventional (clear cell) RCC, chromophobe RCC, and papillary RCC has been previously described. However, the association of oncocytoma with MTSCC has not yet been reported to our knowledge. Herein, we report the first case of a renal collision tumor composed of oncocytoma and MTSCC.

Pseudoangiomatous stromal hyperplasia of the prostate: report of an unprecedented entity in prostate pathology.

Pseudoangiomatous stromal hyperplasia is a benign entity of the breast. It is histologically characterized by open, slit-like spaces lined by spindle cells of myofibroblast/fibroblast differentiation in a dense collagenous stroma. Although pseudoangiomatous stromal hyperplasia has been reported in ectopic breast tissue in anogenital mammary-like glands, it has not been previously reported in non-breast tissues. This includes prostatic tissue, which shares similar histology and pathology with the breast. Herein, we report the first case of prostatic pseudoangiomatous stromal hyperplasia based on histological, immunohistochemical, and electron microscopic findings. The patient was a 74-year-old man with a history of benign prostatic hyperplasia who presented with severe urinary retention and underwent transurethral resection of the prostate. In addition to benign prostatic hyperplasia, the prostate showed areas of irregular spaces lined occasionally by flattened spindle cells in a background of fibrocollagenous stroma. Immunohistochemically, these cells were diffusely positive for vimentin and negative for CD31, CD34, ERG, pancytokeratin, SMA, and D2-40. Electron microscopic findings also showed some cells with fibroblastic features lining these spaces. Given these findings, we postulated that pseudoangiomatous stromal hyperplasia of the prostate has some cells of fibroblastic lineage. Contrary to its breast counterpart where lining cells demonstrate diffusely and strongly positive staining for CD34 and PR, this prostate case showed negative staining for CD34 and PR. These findings indicate potential differences in the histogenesis of prostatic and breast pseudoangiomatous stromal hyperplasia.

Prostatic adenocarcinoma in the setting of persistent müllerian duct syndrome: a case report.

Persistent müllerian duct syndrome (PMDS) is a form of disordered sex development in which rudimentary müllerian structures are identified in phenotypically and genotypically normal males. It is caused by defects in the anti-müllerian hormone (AMH) system. Since patients with PMDS present with undescended testes, testosterone production by Leydig cells later in life is often decreased. The role of androgens in prostate cancerogenesis is well known. Cryptorchid testes and diminished testosterone levels in post-pubertal life in patients with PMDS play a protective role against prostate cancer, and hence, prostate cancer is a rare event in patients with PMDS. Herein, we present a patient who underwent prostatectomy for high-grade prostatic adenocarcinoma with persistent müllerian structures (such as rudimentary uterus, fallopian tubes, and cervix) identified during surgery. To our knowledge, this is the second case reported in the English language literature where PMDS was associated with prostate cancer.

Sarcoid-like granulomas in renal cell carcinoma: The Houston Methodist Hospital experience.

Sarcoid-like (SL) granulomas have been previously described in association with malignant tumors. These granulomas appear to be tumor-related but are not indicative of systemic sarcoidosis, and hence are referred to as SL reactions. These SL reactions can be seen within the primary tumor, its vicinity, or in uninvolved sites such as the spleen, bone marrow, skin, and/or regional lymph nodes draining the tumor. It is a widely held view that SL granulomas are caused by soluble antigenic factors, shed by tumor cells or released due to tumor necrosis. SL reactions reported in Hodgkin lymphoma have been associated with a better prognosis. SL granulomas are thought to play an important role in the host's defenses against metastatic extension. SL granulomas have been reported in approximately 4.4% of carcinomas. Isolated cases of renal cell carcinoma (RCC) with SL granulomas have been reported with questionable prognostic significance. We identified 11 cases of RCCs with SL granulomas. Interestingly, all cases had abundant clear cell cytoplasm (10 clear cell RCC cases and 1 clear cell papillary RCC). We propose that this clear, abundant cytoplasm of the tumor cells with high content of glycogen and lipids may trigger granuloma formation akin to that seen in seminomas with SL granulomas. To date, this is the largest case series of RCCs with SL granulomas.

Primary collision tumors of the kidney composed of oncocytoma and papillary renal cell carcinoma: A review.

BACKGROUND: There are well known cases of hybrid tumors of chromophobe renal cell carcinoma (RCC) and oncocytoma in kidney, where both tumors have the same cell of origin - intercalated cell of the collecting duct. However, collision tumors composed of neoplasms originating from different cell lineages such as oncocytoma and papillary RCC are extremely rare. Herein, we made a collective literature review of reported cases of collision tumors composed of oncocytoma and papillary RCC, adding a case that we recently experienced. MATERIAL AND METHODS: A PubMed database was search for collision tumors of the kidney composed of oncocytoma and papillary RCC and a collective literature review was made. To this cohort, we also added a recently encountered case with similar, confirmed by immunohistochemistry, morphological features. RESULTS: To date 8 cases of a collision tumor composed of papillary RCC and oncocytoma have been described in the literature. All of them had a smaller papillary RCC component present within a larger oncocytoma. CONCLUSION: Because of a few cases of such a collision tumors reported, it is difficult to make classification and right clinical management of these patients. None of the reported cases had tumor recurrence or progression on a follow-up. The presence of only small portion of papillary RCC in a large oncocytoma raises a possibility of under-sampling of malignant component in large oncocytomas in core biopsy or surgically resected specimens. We recommend better sampling, particularly at the periphery of otherwise classic oncocytomas to unveil this possible association.

Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

CONTEXT: - Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. OBJECTIVES: - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? DATA SOURCES: - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. CONCLUSIONS: - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

An isolated inflammatory myofibroblastic tumor of adrenal gland.

Inflammatory myofibroblastic tumor (IMT) is an uncommon lesion that shows a wide range of anatomic distribution. The adrenal gland, however, is a distinctly rare site of occurrence. To date, only a few cases of IMT arising in the adrenal gland have been reported in the English literature. Here, we report another case of isolated adrenal IMT. A 34-year-old man presented to the emergency department with a complaint of a sudden severe right-sided back pain. Subsequent computed tomographic scan imaging studies demonstrated a large right adrenal mass associated with a hematoma. The right adrenal gland was resected. Microscopic examination revealed an encapsulated cellular spindle cell proliferation with a prominent inflammatory infiltrate. Immunohistochemically, those spindle cells were diffusely and strongly positive for anaplastic lymphoma kinase-1, and focally and weakly positive for smooth muscle actin. S-100 protein and cytokeratin were negative. The findings were consistent with IMT arising from the adrenal gland. Although IMTs in the adrenal gland are rare, they should be considered in the differential diagnosis of adrenal masses. The clinical behavior of IMTs in general is currently indeterminate and a close clinical follow-up is recommended. The behavior of adrenal IMTs remains uncertain because of rare reported cases and lack of long-term follow-up. Further follow-up of reported cases and recognition of additional new cases is warranted to unmask the true biological behavior of adrenal IMTs.

Collagenous micronodules in prostate cancer revisited: are they solely associated with Gleason pattern 3 adenocarcinomas?

Collagenous micronodules (CMs) are microscopic stromal nodular eosinophilic fibrillar collagen deposition of uncertain histogenesis seen in prostatic adenocarcinoma. Per the 2005 International Society of Urologic Pathology (ISUP) consensus conference, they are categorized as Gleason pattern 3. This study analyzes morphological and clinical features of CMs from a large series of radical prostatectomies. Hematoxylin and eosin stained slides for 129 radical prostatectomies for adenocarcinoma of prostate with CMs and for 93 prostatic adenocarcinoma cases without CMs as comparison were examined out of a total of 667 cases performed from January 2010 to December 2011 at Houston Methodist Hospital. CMs were identified in 19% of all radical prostatectomies (129/667 cases). Almost all tumors with CMs were located in the peripheral zone (98%) as single or multiple foci of prostatic cancer glands. The vast majority of cases (96%) were identified in association with mucinous secretion. A cribriform Gleason pattern 4 was associated in 86 cases (67%). The CMs were associated with glomerulation (42%) and amphophilic luminal secretion (59%). 88 cases (68%) showed tumor foci with Gleason pattern ≥ 4 in close association with CMs. Multivariate analysis revealed CMs of the prostatic adenocarcinoma are closely related to mucinous secretion, cribriform growth pattern, and Gleason pattern 4. This study suggests that CMs are more frequently associated with Gleason pattern 4 cancer warranting morphologic reappraisal of CMs, rather than the consensus assignment of Gleason pattern 3.

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: more aggressive than previously reported.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid is a rare traditionally "low-grade" tumor that predominantly occurs in women. Approximately 50 cases have been reported in the literature. It arises in a background of Hashimoto thyroiditis and is characterized by nests of epidermoid and mucin-secreting cells located within an eosinophil-rich sclerotic stroma. Herein, we outline the clinicopathological and immunohistochemical characteristics of 6 cases of thyroid SMECE. All tumors were detected in women (age, 36-89 years; average, 59 years), and all patients underwent total thyroidectomies. Clinicopathological findings included extensive tumor invasion into the adjacent soft tissues, trachea, pharynx, and esophagus. Of 6 specimens, 5 had positive surgical margins. Cervical lymph node metastases were seen in 4, and distant metastases were in 3 patients. Immunohistochemically, all tumors were positive for CK19, galectin 3, and p63 and negative for calcitonin, calponin, S-100, and smooth muscle actin. Interestingly, 2 tumors also showed faint focal staining for thyroglobulin, and 2 others had focal positivity for thyroid transcription factor 1. Together, galectin 3 and CK19 expression supported the malignancy of these lesions, and p63 expression raised the possibility that these tumors originated from the ultimobranchial body. In summary, SMECE tumors in our series exhibit a clear female predominance with aggressive behavior and appear to arise from pluripotent solid cell nests. A correct diagnosis is crucial to providing SMECE patients with the appropriate treatment options, and we recommend a closer follow-up schedule than previously considered.