Hemosiderotic fibrohistiocytic lipomatous lesion: clinical correlation with venous stasis

Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) is a recently proposed lipomatous entity. HFLL was originally suggested to be a benign reactive lesion arising due to an antecedent trauma. We report two patients with HFLL who also suffered from chronic vein insufficiency due to varicose involving deep veins of the low limbs. Both patients were middle-aged women with solitary, poorly circumscribed subcutaneous lesions on the lower extremities. Histopathological examination revealed typical features of HFLL. We think that the consistent clinical features such as advanced age, female sex predilection, and specific location along with distinctive histopathological features allow the suggestion that impaired blood circulation, to wit, venous stasis is involved in the pathogenesis of HFLL. We hypothesize that the proliferation of spindled fibroblastic and myofibroblastic cells and capillaries, erythrocyte extravasation, and hemosiderin deposition with lipomatous tissue of HFLL may simply represent an exaggerated tissue response to venous stasis in which elevated venous and capillary pressures, oxygen saturation, and edema stimulate the proliferation of the abovementioned elements and lead to erythrocyte extravasation. A similar histopathological pattern is seen in acroangiodermatitis of Mali and vascular transformation of lymph node sinuses, and these conditions are also associated with impaired blood circulation.     

Hemosiderotic fibrohistiocytic lipomatous lesion: Early pleomorphic hyalinizing angiectatic tumor?

Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) and early pleomorphic hyalinizing angiectatic tumor (PHAT) are characterized histologically by an admixture of fat, moderately cellular fascicles of hemosiderin-laden spindle cells growing in a perivascular, periadipocytic and septal pattern, as well as the presence of macrophages and chronic inflammatory cells. In contrast to a suggested reactive nature of HFLL, PHAT is regarded as a non-metastasizing tumor of uncertain lineage in the recent World Health Organization classification of soft tissue tumors. Reported herein is the case of a 47-year-old woman with an unencapsulated and irregularly circumscribed recurring lesion in the ankle/foot region that developed following ankle distortion and that fulfills histological criteria for both HFLL and early PHAT. In summary, the present case suggests a reactive over-neoplastic nature of HFLL and confirms profound histological similarities with early PHAT. Until more data become available on the biological potential of HFLL/early PHAT, radical surgical excision and follow up of the patient remains the best treatment option.     

Elastofibroma: clonal fibrous proliferation with predominant CD34-positive cells

Elastofibroma is a rare fibrous lesion that most commonly occurs in periscapular soft tissues and is characterized by accumulated abnormal elastic fibers. Although the lesion is generally regarded as a reactive process, an unusual fibroblastic pseudotumor, or as a fibroelastic tumor-like lesion, its etiology remains largely unknown. Recent cytogenetic demonstrations of chromosomal instability and some recurrent or clonal chromosomal changes have raised the possibility that the lesion represents a neoplastic process. We analyzed 14 cases of elastofibroma to further explore, morphologically and genetically, the characteristics of its cellular composition. The interspersed spindle or stellate cells showed a fibroblast-like appearance and were almost consistently positive for vimentin and frequently positive for CD34 and lysozyme immunohistochemically. No spindle cells of myofibroblastic phenotype were recognized. To assess the clonality of the lesions in female patients, the X-linked polymorphic human androgen receptor gene assay was performed using formalin-fixed, paraffin-embedded tissues. A nonrandom inactivation of the androgen receptor gene was detected in two informative cases. Thus, these findings suggest that CD34-positive mesenchymal cells are an integral component of elastofibroma, which represents a clonal fibrous proliferation.     

Sequential Changes in Cell-Mediated Immune Responses to Herpes Simplex Virus After Recurrent Herpetic Infection in Humans

Lymphocyte responses to herpes simplex virus (HSV) were studied in 23 patients with recurrent herpes labialis and in 19 control subjects. Lymphocytes of seropositive, but not seronegative, controls responded to HSV by thymidine incorporation, and the supernatant fluids inhibited the migration of guinea pig macrophages. Lymphocytes from patients with a recurrent herpetic lesion responded to HSV by significantly greater thymidine incorporation than seropositive controls, but supernatants did not show an increased macrophage migration inhibition response. During the 28 days after the onset of a lesion, the thymidine incorporation to HSV fell to the level of the seropositive controls, and supernatants then induced an increased inhibition of macrophage migration. Lymphocyte responses to Candida albicans, purified protein derivative, or phytohemagglutinin did not fluctuate according to the presence of a lesion and did not differ from those of the controls. Lymphocyte responses to HSV were unaffected by culture in the presence of serum from seronegative or seropositive controls, or from patients with or without a herpetic lesion. It is suggested that in patients with recurrent herpes labialis a periodic defect of the migration inhibition response might have allowed the recurrent infection to develop, and that the increased thymidine incorporation stimulated by HSV in vitro is a result of antigenic stimulation from the lesion.     

Hemosiderotic fibrohistiocytic lipomatous lesion: ten cases of a previously undescribed fatty lesion of the foot/ankle.

We address the clinicopathologic features of a previously undescribed heavily-pigmented spindle cell proliferation within a circumscribed benign lipomatous lesion that occurs mainly in the ankle region of older females. Patients with "lipoma with fibrohistiocytic proliferation" were retrieved from our files. Slides and clinical information were reviewed, and immunohistochemistry was performed (n = 5). Ten patients with hemosiderotic fibrohistiocytic lipomatous lesions were identified. All cases demonstrated a well-circumscribed fatty lesion with random focal proliferations of plump, slightly pleomorphic spindled cells, scattered inflammatory cells, and abundant iron pigment. The spindled cells had vesicular nuclei with indistinct nucleoli; occasional hyperchromatism was observed. No nuclear cytoplasmic inclusions were identified. The spindled component had a reactive appearance. In most cases, the fatty component, with homogeneously sized adipocytes, predominated. The lesions occurred in the foot/ankle region (8/10, one each cheek and hand) of primarily females (8/10) with a mean age of 50.6 years (range 42-63 years), size of 7.7 cm (range 2.5-17 cm), and prior duration of 3.1 years. Seven of eight patients had a history of prior trauma. The spindled component was positive for vimentin, calponin, CD34, and occasionally KP-1 or lysozyme and negative for caldesmon, S100, and desmin. Follow-up on eight patients revealed four with recurrences or residual disease over three years, requiring re-excision. No cases metastasized or caused patient death (mean 12 years, range 1-23 years). We describe a predominantly fatty lesion that is hemosiderin rich with a "fibrohistiocytic" proliferation, composed of histiocytes, myofibroblasts, and C34-positive fibroblasts, which occurs predominantly in the ankle region of middle-aged females. We believe that this is a reactive process due to antecedent trauma, the inflammatory cells, hemosiderin, mixed spindled cells, and homogeneous non-neoplastic appearance of the fat. HFLL can be distinguished from previously described lesions. Correct identification of hemosiderotic fibrohistiocytic lipomatous lesion is important, as it may locally recur.     

A case of secondary malignant giant-cell tumor of bone with p53 mutation after long-term follow-up

A 46-year-old man was admitted to the hospital with a recurrent giant-cell tumor of the distal femur. This was his fourth recurrence, and it had occurred 16 years after his last treatment. The resected recurrent tumor was histologically determined to be a conventional giant-cell tumor. However, a single lung metastatic lesion and local recurrence were noticed 6 months after the resection, both of which were surgically excised. The lung lesion was histologically determined to be an implantation of giant-cell tumor, whereas the local recurrent lesion contained a clearly separated fibrosarcomatous area within the conventional giant-cell tumor. Immunohistochemistry showed diffuse and strong p53 expression in the fibrosarcomatous area. Direct sequencing revealed a p53 mutation in the sarcomatous area and a recessive mutant signal in the conventional area. The lung lesion also contained the same p53 mutation. Identification of the p53 mutation may help in diagnosing potential malignant transformation of giant-cell tumor.     

Invasive carcinoma arising from sclerosing polycystic adenosis of the salivary gland

Sclerosing polycystic adenosis is a rare salivary gland lesion. Recently, this entity has been regarded as a neoplastic lesion of low-grade malignant potential but, to date, no invasive carcinoma, metastases, or associated mortality have been reported. We report the first case of an invasive carcinoma component in a recurrent sclerosing polycystic adenosis lesion.     

Micronodular hyperplasia of type II pneumocytes-a new lung lesion associated with tuberous sclerosis

Open lung biopsy in a 38-year-old female with Pringle-Bourneville syndrome and recurrent pneumothorax revealed a micronodular pneumocyte II hyperplasia, a new entity probably associated with the tuberous sclerosis syndrome. The lesion caused an obstruction of the alveolar lymphatic vessels and alveolar ducts, resulting in an emphysema-like picture. This cystic dilation of alveoli and draining lymphatics followed by rupture caused the recurrent pneumothorax. The epithelial pneumocytic nature of the lesion was confirmed by immunohistochemistry and electronmicroscopy.     

NEPHROGENIC ADENOMA IN FEMALE URETHRA

A case of a 66 years old female who had a nephrogenic adenoma recurring three times during a 6 months course of her illness is reported. With each recurrence, the lesion moved toward the urethral orifice, suggesting an intimate relationship between the recurrent process and physical stimuli to the mucosa. Electron microscopy revealed merely non-specific morphological features of epithelial cells in the lesion.
There were no positive morphological clues in the lesion for supporting the lesion to resemble mesonephric and/or mesodermal tissue. The diagnostic term of tubular metaplasia for the lesion is preferable instead of nephrogenic adenoma.     

Benign fibrohistiocytoma (xanthomatous variant) of the acromion. A case report and review of the literature

A number of fibrous lesions involving bone display almost identical histologic appearances yet may represent either reactive or neoplastic conditions, resulting in a confusing nomenclature and possible diagnostic confusion. We report the case of a young man with no significant previous medical history who presented with a painful lesion in the left shoulder, which consisted almost entirely of xanthomatous material. We discuss the possible differential diagnosis of this lesion and why benign fibrous histiocytoma is the preferred terminology for this lesion. To our knowledge, this is the first reported case of a benign fibrous histiocytoma involving the acromion in an adult.     

Ultrastructure of transplant glomerulopathy

Thirty-one specimens of tissue were obtained from 15 renal allografts 3–96 months after transplantation and studied by light, electron and in some cases also by immunofluorescence microscopy. All patients had a degree of renal insufficiency and almost all had proteinuria and moderate hypertension; nephrotic syndrome was present in one and hematuria in two. On histological examination one patient showed cellular proliferation suggestive of glomerulonephritis (recurrent or de novo ) and another patient had numerous crescents. The most frequent glomerular lesion was widening of the lamina rara interna with subendothelial accumulation of finely granular material, formation of new subendothelial basement membrane and deposition of microfibrils and fine filaments. The mesangial changes were mainly those of mesangiolysis and mesangial sclerosis with deposition of mesangial matrix and microfibrils, but little cellular proliferation. Fragmented red blood cells were seen in nearly half of the patients. In another seven patients the lesion resembled focal segmental glomerulosclerosis. This combination of changes termed transplant glomerulopathy leads to diffuse glomerular sclerosis. Arterial intimal thickening and occasionally also thrombosis produced ischaemic changes in the kidney and in the glomeruli and contributed significantly to the process of transplant rejection.     

Pelvic recurrence of an ovarian seromucinous borderline tumor detected by vaginal cytology: A case report and review of the literature

Seromucinous borderline tumors are typically confined to the ovaries and rarely relapse after surgery. We report the case of a woman with a seromucinous borderline tumor with peritoneal implant at the Douglas pouch, who was affected by a recurrent tumor at the vaginal stump 2 years and 6 months after the primary surgery. The recurrent lesion was detected by vaginal cytology. Histology of the recurrent lesion showed perineural infiltration, and progression to low‐grade adenocarcinoma was suggested. After the second surgery, vaginal cytology showed that the tumor cells remained positive. At postoperative follow‐ups of ovarian borderline tumors, an examination of the specific region where recurrence is likely to occur can contribute to the early detection of tumor relapse. Diagn. Cytopathol. 2016;44:912–916. © 2016 Wiley Periodicals, Inc.     

Central mucoepidermoid carcinoma arising from glandular odontogenic cyst confirmed by analysis of MAML2 rearrangement: A case report

Central mucoepidermoid carcinoma (MEC) poses a diagnostic challenge because of its rarity and histological overlap with glandular odontogenic cyst (GOC). In MEC of both salivary glands and jaws, MAML2 arrangement has been well known as the specific gene alteration. We report a case of central MEC arising from GOC diagnosed by MAML2 fusion gene. A 57‐year‐old male presented a multilocular cystic lesion in left molar region of the mandible. Histopathologically, multiple cysts lined by thin cuboidal or non‐keratinized squamous epithelium with small duct‐like structures, mucous cells and ciliated cells were present. It was diagnosed as GOC. The recurrent lesion after nine years showed the proliferation of many cystic and solid nests composed of epidermoid, mucous and intermediated cells. Nested PCR revealed CRTC3‐MAML2 fusion gene in the recurrent lesion, but not in the primary one. Similarly, MAML‐2 rearrangement by FISH analysis was positive in the recurrent lesion, while negative for the primary one, thus confirming the diagnosis of central MEC arising from GOC. Analysis of MAML2 rearrangement can be used as a supportive evidence to distinguish central MEC from GOC.     

Recurrent inflammatory myofibroblastic tumors harboring PIK3CA and KIT mutations

Inflammatory myofibroblastic tumour (IMT) is a relatively rare soft tissue malignancy. It exhibits locally aggressive behavior with a tendency for local recurrence and rare metastasis, and rare recurrent IMTs may show histological progression. The genetic hallmark of IMT is ALK rearrangement from chromosome arm 2p, but gene mutations involved in IMT remain poorly understood. The aim of the present study was to perform a pairwise comparison of the gene mutations occurring in primary and recurrent IMT from the same patient. We conducted a high-throughput analysis of 238 known mutations of 19 oncogenes in pairwise comparison primary and recurrent samples from 2 patients of IMT using Sequenom MassARRAY technology. Our results revealed 2 mutations in 2 recurrent lesion samples, including one in exon 11 of the KIT gene, resulting in a T-C substitution at position 1727 (L576P), the recurrent sample underwent histologic progression with “pleomorphic undifferentiated sarcoma-like” transformation; the other mutation was in exon 19 of the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, resulting in a G-A substitution at position 1624 (E542K). Moreover, no any mutation was found in the primary lesion samples from 2 patients. Our findings suggest that variable genome changes might be present in IMT, especially during the progression from a primary tumour to recurrence. To the best of our knowledge, no such longitudinal study of IMT has been undertaken previously.     

Composite dermatofibrosarcoma protuberans-giant cell fibroblastoma recurring as Bednár tumor-giant cell fibroblastoma with mucoid lakes and with amputation neuroma

We report an unusual case of composite giant cell fibroblastoma-dermatofibrosarcoma protuberans (DFSP) that, in its second recurrence, contained a pattern of Bednár tumor (BT) and giant cell fibroblastoma (GCF). The recurrent tumor showed extreme myxoid change with creation of mucoid lakes, which mimicked a pattern of myxoid liposarcoma. One area in the recurrent lesion contained amputation neuroma overgrown with neoplastic spindle cells, which simulated a nerve sheath neoplasm. This case demonstrates common histogenesis of GCF, DFSP and BT, and it shows how broad morphological spectrum can be produced by a composite tumor, especially when the tumor includes unconventional growth pattern or additional non-neoplastic lesion.     

Recurrent respiratory papillomatosis complicated by aspergillosis: a case report with review of literature

Pulmonary extension of recurrent invasive papillomatosis often poses a diagnostic challenge to the examining bronchoscopist, pathologist, radiologist and surgeon, in distinguishing it as a benign lesion that is confined to the mucosa and extending along the branches of the tracheobronchial tree from true invasion of a malignant tumor. We document here a case of recurrent invasive respiratory papillomatosis which initially presented as a laryngeal papilloma. After multiple recurrences, the patient presented with bronchopulmonary involvement, complicated by invasive aspergillosis in a non-immunocompromised setting.     

Massive ovarian edema: a nonneoplastic pelvic mass of young women

Two cases of massive ovarian edema are reported in addition to the eight previous cases published in the English literature. The predominance of the right-sided involvement and the histopathological characteristics of this lesion support the hypothesis that the basic pathogenetic mechanism is an impairment of the venous and lymphatic drainage of the ovary, triggered by recurrent partial torsion of the mesovarium. This nonneoplastic lesion should be recognized as a distinct entity in ovarian disease and treated conservatively.     

The recurrence risk for neural tube defects in the United States: A collaborative study

To determine the recurrence risk for patients with one prior pregnancy affected with neural tube defects (NTD), the authors have pooled date from eight testing centers. In 831 pregnancies studies because one sib was affected with an NTD, the recurrence rate was 3.0%, with 95% confidence limits of 2.0–4.3%, and 99% confidence limits of 1.8–4.8%. The recurrent lesion, whether spina bifida or anencephaly, tended to be concordant with the first to a significant degree. Only 12.2% or recurrent NTD were different from the first, with 95% confidence limits of 4.1–26.2%, and 99% confidence limits of 1.7–30.9%. Both an accurate recurrence risk and the information that a recurrent NTD lesion tends to be concordant with that in the first asffected child are useful in the genetic counseling of patients in the United States and in the selecton of appropriate prenatal diagnostic studies.     

Benign mesenchymal liver hamartoma in an adult male: a case report and review of the literature

Mesenchymal hamartoma of the liver is an uncommon benign lesion seen almost exclusively in children younger than two years of age. The first case was reported in 1903, and until now fewer than 200 cases have been reported. A 38-year-old male complaining of dull subcostal pain lasting for almost 10 months was found on abdominal ultrasound to have a focal lesion of the liver. He was referred to our Unit where imaging procedures (ultrasound and computed tomography) revealed a solid lesion, 8 centimeters in diameter, located in the IVb and V segments of the liver. There were no clear margins between the lesion and the gallbladder wall. Alpha-fetoprotein and carcinoembryonic antigen were within normal limits and carbohydrate antigen 19-9 was minimally elevated. There was no evidence of metastatic disease. Ultrasound-guided biopsy of the lesion was done and pathology report of a biopsy specimen suggested that the tumor was probably a benign mesenchymal hamartoma. The patient underwent a formal bi-segmentectomy (IVb and V segments) with cholecystectomy. Definitive pathology report confirmed the diagnosis of a benign mesenchymal hamartoma.     

Pleomorphic hyalinizing angiectatic tumor with a sarcomatous component recurring as high-grade myxofibrosarcoma

Pleomorphic hyalinizing angiectatic tumor (PHAT) of the soft tissue is a rare distinctive tumor listed as a benign neoplasm in the new World Health Organization classification. It may recur and most reported recurrent tumors retained the typical morphological appearance of PHAT; rare tumors recurred with the appearance of a sarcoma. Reported herein is an additional example of recurrent PHAT, but in contrast to the previously described cases the present tumor morphologically qualified as a sarcoma from the very beginning; it recurred as a high-grade myxofibrosarcoma. A 76-year-old woman presented with a solitary subcutaneous tumor in the axilla that was surgically removed. Seven months later, the patient experienced a local recurrence. Microscopically, the typical features of PHAT were identified in the initial lesion, namely hyalinized, fibrin-containing vessels and pleomorphic stromal cells; there were areas of hemorrhage and necrosis. Additionally, peripherally located areas of the tumor manifested highly pleomorphic cells with frequent atypical mitoses, producing a sarcomatous appearance. The mitotic index in the sarcomatous part was 1/10 high-power fields (HPF). Hyalinized, fibrin-containing vessels were absent in these sarcomatous areas, and the stroma was myxoid. The recurrent lesion was composed of large highly pleomorphic oval, round, spindled or bizarre cells with a high mitotic rate, ranging from 3/10 HPF to 7/10 HPF. The neoplastic cells were arranged haphazardly in a myxoid matrix. Hyalinized, fibrin-containing vessels typical for PHAT were absent. PHAT may be more aggressive than previously thought, and PHAT may encompass a morphological spectrum of the lesion ranging from benign to malignant.