Carcinoma in a solitary intraductal papilloma of the breast

Herein is reported a rare case of carcinoma arising from papilloma of the breast. A 63-year-old postmenopausal woman noticed a nodule approximately 1 cm in diameter in her left breast. Ultrasonography indicated a mass with a solid pattern within an intracystic tumor measuring 1.5 × 1.5 × 1.4 cm in diameter located near the left nipple. On total image analysis malignancy could not be denied, therefore lumpectomy with resection of the surrounding tissue was performed. Histologically the tumor consisted of cancerous and papilloma components. The cancer cells had high-grade nuclear atypia, were irregular, and contained abundant eosinophilic cytoplasm with a thin vascular stalk. In contrast, the tumor cells had no atypia, and had a thick stroma in the papilloma components. Both lesions could be distinguished clearly from each other. In addition, a transition from papillary to cancerous elements in some areas was seen. An additional partial mastectomy was performed after the lumpectomy but no carcinoma foci were noted in the excised tissue. Possible occurrence of cancerous change in solitary intraductal papilloma of the breast was suspected.     

Solitary amyloid tumour of breast--a case report

45 years old woman with solitary amyloid tumor of breast is described. Clinically, the breast mass was hard and was suspicious of carcinoma. Microscopically there was no neoplasia. Instead there was extensive fibrosis with amyloid deposition in perivascular periductal areas and also in intervening stroma. The presence of amyloid was confirmed by Special stains and by Polarised microscope. Investigations revealed no evidence of systemic amyloidosis or amyloid related illness.     

Bilateral cystosarcoma phyllodes of the breast: a case report of malignant form with contralateral benign form

Bilateral cystosarcoma phyllode is uncommon; bilateral tumors, either synchronous or metachronous, are generally either benign or malignant. We report one case of bilateral synchronous cystosarcoma phyllode in a 32-year-old pregnant woman. The left breast mass, measuring 21 x 17 x 10 cm, was classified as malignant cystosarcoma phyllode (high cellularity, stromal overgrowth, marked nuclear atypia, necrosis, mitotic rate = 4 mitoses/10 high power field, infiltrative margin). The right 9 x 9 cm mass was a benign cystosarcoma phyllode tumor (low to moderate cellularity, discrete nuclear atypia, mitotic rate = 1 mitoses/10 high power field, no necrosis, pushing margin). The patient had a left-sided mastectomy and a complete local excision with clear margin of the right breast mass. The patient is free of disease with a 17-month follow-up.     

Nodular glomerulopathy associated with nonamyloidotic kappa light chain deposits and excess immunoglobulin light chain synthesis

A nodular glomerulopathy characterized by mesangial deposits of monoclonal kappa light chains was detected by immunofluorescence in a renal biopsy from a patient with proteinuria and hypertension. These nodules lacked the tinctorial and morphologic features of amyloid. Ultrastructurally, the nodules contained electron-dense granular deposits as well as fibrils in parallel arrangement. The fibrils measured 110-140 A in diameter. They were consistent in size with amyloid fibrils. However, they differed in lacking the randomly oriented network of typical amyloid fibrils and more closely resembled fibrils intrinsic to mesangial matrix. The patient had no bone marrow or X-ray evidence of myeloma and no evidence of free monoclonal light chains in serum or concentrated urines. Biosynthetic studies of the patient's bone marrow cells demonstrated unbalanced immunoglobulin synthesis with excess production of monoclonal kappa light chains. These observations suggest that the observed glomerulopathy results from direct deposition of monoclonal light chains. Deposits with kappa light chain determinants have been found in 7 other patients with similar nodular glomerulopathies, 4 of whom had diagnosed clinical myeloma. The lesion of nonamyloidotic nodular glomerulopathy previously described in 19 patients, nor examined by immunopathologic techniques or not shown to contain light chain determinants, may have a similar pathogenesis.     

Unilateral gestational macromastia--a rare disorder

Macromastia is the massive enlargement of the breast, unilateral or bilateral, disproportionate to the growth of the rest of the body. It is called gravid macromastia or gigantomastia of pregnancy when it occurs during pregnancy. It may or may not regress following parturition. Gestational macromastia is exceptionally rare. We report a 28-year-old female with gigantomastia of the left breast. She presented at four months post-partum with painful massive enlargement of the left breast since the third month of pregnancy. The overlying skin was stretched out and showed multiple ulcers with foul smelling discharge. The nipple and areola were unremarkable. Simple mastectomy was done, as fine needle aspiration cytology was suggestive of phylloides tumour. The breast specimen measured 30 x 30 x 9 cm and was replaced totally by grey-white tissue involving all the resection margins. No normal breast tissue or fat was identified. Histopathology showed periductal as well as diffuse fibrosis, adenosis and lactational changes. No features of phylloides tumour or carcinoma were present and it was diagnosed as unilateral gestational macromastia.     

Primary diffuse tracheobronchial amyloidosis in a dog

Primary diffuse tracheobronchial amyloidosis was diagnosed at necropsy in an intact male Akita dog aged 11 years, a non-productive chronic cough having been the only related clinical sign. Histologically, eosinophilic hyalinized deposits were found as a band in the lamina propria underneath the epithelium of the trachea and bronchi. When stained with Congo red, apple-green birefringence was observed in the deposits viewed with polarized light. The amyloid did not lose sensitivity to Congo red staining after incubation with potassium permanganate, indicating that it was of the AL (amyloid light chain) type. Ultrastructural features of the amyloid included a typical fibrillar meshwork with individual fibrils measuring 9.5 to 10.5 nm in diameter. This is the first report of primary diffuse tracheobronchial amyloidosis in the dog.     

Localized amyloidosis in squamous cell carcinoma of uterine cervix: Electron microscopic features of nodular and star-like amyloid deposits

An ultrastructural study of amyloid deposits in four cases of squamous cell carcinoma of uterine cervix was performed. The amyloid deposits reacted with anti-keratin antiserum on frozen sections. Amyloid deposits showed nodular (4 cases) and star-like forms (3 cases). Nodular amyloid deposits were composed of slightly whorled fibrils, measuring 7–10 nm in width. Some of them contained cellular debris and thicker, more electron-dense filaments than amyloid fibrils. In three cases, filamentous tumour cells and filamentous masses were observed together with amyloid. Star-like amyloid deposits were composed of bundles of straight amyloid fibrils. Some of the tumour cells in contact with star-like amyloid deposits had deep cytoplasmic invaginations, where closely packed amyloid fibrils were arrayed in parallel fasion. In addition, a few tumour cells had membrane-bound amyloid fibrils in the cytoplasm. It is suggested that nodular amyloid deposits are derived from the tumour cells through filamentous degeneration. Amyloid fibrils in star-like amyloid deposits are thought to be formed within the cytoplasm or in the vicinity of invaginated cytoplasmic membranes of the tumour cells.     

Primary bilateral mucosa-associated lymphoid tissue lymphoma of the breast with atypical ductal hyperplasia and localized amyloidosis. A case report and review of the literature

Primary non-Hodgkin lymphoma of the breast is a rare disease. Primary mucosa-associated lymphoid tissue lymphoma is even rarer, and bilateral involvement is exceptional. We describe a case of primary bilateral breast mucosa-associated lymphoid tissue lymphoma with bilateral atypical ductal hyperplasia and bilateral localized amyloidosis in a 64-year-old woman with a history of arthritis and systemic lupus erythematosus and its clinical, histologic, and immunohistochemical features. Microscopic examination of the breast lesion showed dense periductal and perilobular small and plasmacytoid lymphocytes with eosinophilic amyloid in the vessels and the stroma. Bilateral single foci of atypical ductal hyperplasia were also noted. Fine needle aspiration showed small and large lymphocytes and plasma cells. Molecular analysis demonstrated a heavy chain immunoglobulin H gene rearrangement. Flow cytometry studies showed an abnormal B-cell population. The combined histologic, paraffin immunohistochemistry, flow cytometry, and molecular results were considered diagnostic for low-grade mucosa-associated lymphoid tissue lymphoma. The patient underwent bilateral local breast radiation without other organ or site involvement.     

Medullary breast carcinoma: a case report with cytological features and histological confirmation

We report the case of a 83-year-old woman who presented with a left-breast lump. On physical examination the patient had a well-demarcated mass located in the upper outer quadrant of her left breast with a palpable unilateral axillary lymph node. Mammography and ultrasonography depicted a heterogeneous well-defined lesion measuring 6 cm in diameter without calcifications. Fine-needle aspiration cytology of the lesion was performed. Cytological examination revealed highly cellular smears containing large atypical cells arranged in syncytial sheets and intimately admixed with lymphocytes and neutrophils. The nuclear to cytoplasmic ratio was high in tumor cells whose nucleus exhibited coarse chromatin with one or more conspicuous nucleoli. The diagnosis of medullary breast carcinoma, which was strongly suspected by cytology, was confirmed by histological examination of the surgical specimen after a modified radical mastectomy with axillary dissection.     

An electron microscopic study on digestive tract amyloidosis in ferric nitrilotriacetate (Fe-NTA)-induced "F1 amyloidosis" mice

The histological distribution and ultrastructural findings were investigated in 52 amyloid-positive cases obtained from 80 F1 mice (32 males and 48 females) receiving 126 to 502 daily intraperitoneal injections of ferric nitrilotriacetic acid (Fe-NTA) resulting from reciprocal crossing of 20 parental mice receiving daily intraperitoneal injections of Fe-NTA for 5 months. Of 52 amyloidotic F1 mice 49 (94%) developed a moderate degree of amyloid deposits in the gastrointestinal tract. Moderate amounts of amyloid deposits were sporadically discernible in the lamina propria of the stomach pars glandularis, the duodenal mucosa, and to a lesser extent in that of the rectal mucosa. Electron microscopic observation revealed that macrophages adjacent to amyloid mass were radiating outward abundant bundles of non-branching amyloid fibrils from the cytoplasmic invaginations. In the cytoplasm of the macrophages there were occasionally acid phosphatase-positive lysosomes including amyloid fibrils measuring approximately 100 A in width. Moreover, it is discussed whether fibroblasts or fibroblast-like interstitial cells are involved in amyloid formation.     

Contribution of human smooth muscle cells to amyloid angiopathy in AL (light-chain) amyloidosis

Objective: Amyloid light-chain (AL) amyloidosis is a disease process that often compromises the peripheral vascular system and leads to systemic end-organ dysfunction. Although amyloid formation in vessel walls is a multifaceted process, the assembly of the native light chains (LCs) into amyloid fibrils is central to its pathogenesis. Recent evidence suggests that endocytosis and endolysosomal processing of immunoglobin LCs by host cells is essential to the formation of amyloid fibrils that are deposited in at least some tissues. The aim of this study was to elucidate the role of vascular smooth muscle in amyloid angiopathy. Methods: Human coronary artery smooth muscle cells (SMCs) were grown on coverslips, four chamber glass slides, and growth factor-reduced Matrigel matrix in the presence of 10 µg/ml of ALs (λ and κ isotypes), nonamyloidogenic LCs, and culture medium (negative control) for 48 and 72 hours. Thereafter, a detailed light microscopic, immunohistochemical, and ultrastructural evaluation was conducted to verify amyloid deposition and characterize the role of SMCs in the formation of amyloid deposits in the various experimental conditions. Results: Amyloid deposits were detected extracellulary as early as 48 hours after exposure of vascular smooth muscle cells (VSMCs) to AL-LCs (amyloidogenic light chains) as confirmed by affinity to Congo red dye, thioflavin T fluorescence, and transmission electron microscopy. No amyloid was present in the cultures of SMCs treated with medium alone or nonamyloidogenic LCs. SMCs associated with amyloid deposits exhibited CD68, lysosome-associated membrane protein 1-1, and intracellular lambda light chain expression and only focal smooth muscle actin and muscle-specific actin positivity. Electron microscopy revealed these cells to have an expanded mature lysosomal compartment closely associated with deposits of newly formed amyloid fibrils. Conclusions: The interaction of amyloidogenic LCs with VSMCs is necessary for the formation of amyloid fibrils that are deposited in peripheral vessels. VSMCs participate in the formation of amyloid by the intracellular processing of AL-LCs, which is possible due to their transformation from a smooth muscle to a macrophage phenotype. The formation of amyloid fibrils occurs in the mature lysosomal compartment of transformed cells. The amyloid that is formed is then extruded into the extracellular matrix.     

Malignant adenomyoepithelioma of the breast with matrix production may be compatible with one variant form of matrix-producing carcinoma: a case report

We examined a 77-year-old woman who suffered from a left breast tumor. She had undergone right mastectomy for invasive ductal carcinoma at 68 years of age, and rectal resection for mucinous carcinoma at the age of 74 years. The left breast tumor measured 3.8x2.5x1.6cm. Neoplastic cells consisted of atypical epithelial and myoepithelial cells. The former cells were polygonal and large. They were located in the periphery of the tumor, arranged in a ductal pattern, and expressed cytokeratins, S-100 protein, maspin, and MIC2. The latter cells were composed of dark cells which proliferated in a periductal pattern, and stellate cells which were located in the center of the tumor. They invaded the chondromyxoid tissues, and proliferated in a lace-like pattern. Atypical myoepithelial cells expressed vimentin, S-100 protein, maspin, and MIC2. We conclude that malignant adenomyoepithelioma of the breast with matrix production might be compatible with a variant form of matrix-producing carcinoma.     

Low-grade periductal stromal sarcoma of the breast with myxoid features: Immunohistochemistry

A 52-year-old woman was admitted with a painful right breast tumor measuring more than 20 cm in largest diameter, which ulcerated the overlying skin. The lesion had appeared 4 years previously but the patient hesitated to seek medical care due to 'fear of cancer'. Microscopically, the tumor was composed of spindle cells that formed cuffs around multiple open tubules and ducts set in an abundant, myxoid stroma. The spindle cells had significant atypia with nuclear pleomorphism, occasional cytoplasmic vacuolation and moderate mitotic activity. The ducts and lobules surrounded by the proliferating tumor cells had minimal distortion, with a pericanalicular growth pattern devoid of the phyllodes pattern. The tumor had a multinodular growth pattern with coalesced and individual tumor nodules, the latter being found mostly at the periphery of the lesion. On immunohistochemistry the tumor cells were positive for smooth muscle actin, CD34, and vimentin, and focally positive for CD10. A diagnosis of low-grade periductal stromal sarcoma (PDSS) with myxoid features was established. PDSS is a distinct low-grade breast sarcoma, the appropriate diagnosis of which requires extensive tumor sampling and additional broad immunohistochemistry. PDSS should not be confused with other spindle cell breast tumors because they require different treatment.     

Localized amyloidosis of the uterine cervix

Summary Localized amyloidosis of the uterine cervix was found in a 56-year-old woman. The firm enlarged cervix showed massive tumorous amyloid deposition. In the amyloid deposits there were foci of ossification and calcification. An infiltrate of multinucleated giant cells, histiocytes, lymphocytes, and plasma cells was seen adjacent to the amyloid deposits. Immunohistochemically, the amyloid reacted with antisera against A-lambda, amyloid protein of immunoglobulin lambda light chain origin. This indicated that the amyloid protein was of immunoglobulin origin in this rare case of localized amyloidosis of the uterine cervix.     

Relationship between amyloid deposition and intracellular structural changes in familial amyloidotic polyneuropathy

Transthyretin-related familial amyloidotic polyneuropathy is a systemic amyloidosis caused by mutations in the transthyretin gene. Extracellular deposition of amyloid is the common pathologic hallmark of amyloidoses including Alzheimer disease, AL amyloidosis, AA amyloidosis, and familial amyloidotic polyneuropathy. However, the exact relationship between amyloid deposition and cell death has not yet been clarified. To elucidate this relationship, we studied the effect of transthyretin amyloid fibrils and prefibrillar aggregates on cells by using autopsy tissues obtained from 8 patients with familial amyloidotic polyneuropathy, as well as cultured cell lines. Ultrastructural studies of amyloid-laden cardiomyocytes showed that intracellular structural changes correlated with the degree of amyloid deposition and may reflect metabolic disturbances caused by physical limitations imposed by the amyloid deposits. Amyloid-laden vascular endothelial cells, mesangial cells, smooth muscle cells, Schwann cells, and cardiomyocytes, however, had well-preserved cell nuclei and showed no apoptotic changes, even when cells were completely surrounded by prefibrillar transthyretin aggregates and amyloid fibrils. Synthesized prefibrillar transthyretin aggregates, transthyretin fibrils, and amyloid fibrils obtained from patients with familial amyloidotic polyneuropathy evidenced no cytotoxicity in cell culture experiments. Our data thus indicate that neither transthyretin amyloid fibrils nor prefibrillar transthyretin aggregates directly induced apoptosis. However, cellular metabolic disturbances caused by cells' being physically confined by amyloid deposits may induce cell degeneration.     

Nonamyloidotic monoclonal immunoglobulin deposits lack amyloid P component

Deposits in tissues from 13 patients with amyloid, 8 with monoclonal light chain or light and heavy chain deposition disease, and 2 with both amyloid and nonamyloidotic light chain deposits of the same isotype were examined in parallel for the presence of amyloid P component by immunofluorescence and/or immunoperoxidase methods. Amyloid P component was detected in the amyloid but not the nonamyloid deposits, even in the 2 individuals in whom both types of deposits were present, indicating a specific relationship between the amyloid P component and the amyloid fibrils.     

Multinodular deposition of AA-type amyloid localized in the adrenal glands of an old man.

Multinodular amyloid deposits localized in non-neoplastic adrenal glands were found incidentally at autopsy in an 83-year-old Japanese man. Clinically, the patient lacked evident deficiency of adrenal hormones. The nodules of the stromal amyloid deposits were scattered in the adrenal cortex, where the parenchymal cells were compressed and atrophic. The deposits were confirmed to be amyloid by Congo red staining and polarization microscopy. Amyloid fibrils were also demonstrated in the deposits by electron microscopy. The amyloid deposits were permanganate-sensitive and showed immunohistochemical staining for serum amyloid P component and serum amyloid A protein (SAA), implying that they were AA amyloid. There have been no reports describing localized amyloid deposits of the AA type in non-neoplastic adrenal glands. The pathogenesis and clinical significance of the amyloid deposition in the present case remain only speculative.     

Obstructive jaundice caused by the deposition of amyloid-like substances in the extrahepatic and large intrahepatic bile ducts in a patient with multiple myeloma

Obstructive jaundice has rarely been reported in liver amyloidosis. We report here an autopsy of a 55-year-old woman with multiple myeloma and obstructive jaundice due to the deposition of amyloid-like substances in the walls and lumina of the extrahepatic bile duct and intrahepatic large bile ducts, resulting in obstruction and narrowing of the bile ducts. The amyloid-like deposits were negative with Congo red stain, and were negative immunohistochemically for IgG, IgA, IgM, kappa chain, beta-2-microglobulin, and amyloid A and P components. However, they were positive for lambda chain, and ultrastructurally composed of non-branching filaments with a diameter of 7–10 nm. This is the first case of obstructive jaundice due to histologically confirmed amyloid-like deposits in the biliary system.     

Multinodular Deposition of AA-type Amyloid Localized in the Adrenal Glands of an Old Man

Multinodular amyloid deposits localized in non neoplastic adrenal glands were found incidentally at autopsy in an 83-year-old Japanese man. Clinically, the patient lacked evident deficiency of adrenal hormones. The nodules of the stromal amyloid deposits were scattered in the adrenal cortex, where the parenchymal cells were compressed and atrophic. The deposits were confirmed to be amyloid by Congo red staining and polarization microscopy. Amyloid fibrils were also demonstrated in the deposits by electron microscopy. The amyloid deposits were permanganate-sensitive and showed immunohistochemical staining for serum amyloid P component and serum amyloid A protein (SAA), implying that they were AA amyloid. There have been no reports describing localized amyloid deposits of the AA type in non neoplastic adrenal glands. The patho-genesis and clinical significance of the amyloid deposition in the present case remain only speculative. Acta Pathol Jpn 42: 893–896, 1992.     

Early pathogenesis of cardiac amyloid deposition in senile systemic amyloidosis: close relationship between amyloid deposits and the basement membranes of myocardial cells

Despite a number of in vitro studies of transthyretin (TTR) amyloidogenesis the early stage of in vivo amyloidogenesis in the human heart is largely unknown. A heart with a mild degree of cardiac amyloidosis removed from a 90-year old woman at autopsy was selected for analysis. The genotype of the TTR was the wild type. An immunohistochemical study with anti-TTR antibody was performed on serial paraffin sections, and 17 TTR-positive lesions less than 50 micro m in diameter consisting of 13 interstitial and 4 vascular lesions were identified. The early interstitial lesions start as thick membranous deposits between interfacing myocardial cells. They are Congophilic with green birefringence and positive for apolipoprotein E but negative for amyloid P component. The TTR-positive amyloid extends along intercellular spaces and becomes larger, involving several myocardial fibers. The media is the initial site of arteriolar involvement. According to the in vitro studies of amyloid fibrillogenesis, the most critical step is formation of the nucleus under supersaturated conditions. The supersaturated conditions are speculated to be achieved by binding to proteoglycans or lipid membranes. Our results indicate that the basement membrane of myocardial cells is the initial site of amyloid deposition, providing a suitable place for concentration of TTR.