Invasive ductal carcinoma of the breast associated with extensive melanin melanosis: a case report and review of the literature

Extensive melanosis of breast tissue due to melanin in the absence of involvement by melanoma either primary or secondary has been rarely encountered. Herein we report a first and unique case of extensive macroscopic and microscopic melanosis of mammary parenchyma between carcinoma cells due to melanin in a patient with a poorly differentiated invasive ductal carcinoma of the breast with no evidence of melanocytic differentiation or melanoma. In contrast to previously reported cases in the literature, there is no breach of dermal-epidermal junction and there is no dermal infiltrate in the skin overlying the carcinoma, or Pagetoid disease in the nipple.     

Pulmonary tumor thrombotic microangiopathy associated with extramammary Paget's disease: An autopsy case report

Pulmonary tumor thrombotic microangiopathy (PTTM) is histologically characterized by micro tumor cell embolism and intimal fibrocellular proliferation of pulmonary arteries or arterioles. We report a secondary case of PTTM associated with extramammary Paget's disease (EMPD). The patient was a 72‐year‐old man with exertional dyspnea. Clinical examinations found he had pulmonary hypertension and multiple osteolytic lesions of vertebra. Cytological analysis of pulmonary wedge artery sample detected malignant cells and he was dead before treatment was started. Multiple tumor embolisms (>17) were identified in pulmonary arteries or arterioles at autopsy, consistent with PTTM. Metastatic nodules were found in liver and lymph node. Furthermore, disseminated carcinomatosis of the bone marrow (DCBM) was seen. Immunostaining results pointed out that tumor cells possessed mammary gland phenotype. He had 4‐years history of EMPD in the left axilla without recurrence, and immunohistochemistry results were the same as the autopsy specimen. Thus, we diagnosed the primary site of PTTM to be EMPD. Our case highlights the usefulness of the recent proposed classification of PTTM, potential association between PTTM and DCBM, and the necessity for long‐term follow‐up in EMPD. EMPD can rarely cause PTTM to manifest as a paraneoplastic syndrome.     

Peritoneal melanosis combined with serous cystadenoma of the ovary: a case report and literature review

Benign peritoneal melanosis is extremely rare and traditionally occurs in association with ovarian dermoid cysts, but rarely with peritoneal cyst, enteric duplication cyst or gastric triplication. The pathogenesis of peritoneal melanosis, in particular, the origin of the pigment-producing cells is unclear. We describe a case of peritoneal melanosis that was associated with ovarian serous cystadenoma in a young woman. Ovarian serous cystadenoma has not been previously described as a combined lesion of peritoneal melanosis. Based on the extremely rare incidence of this lesion and heterogeneous combined lesions, the possibility of an incidentally found, coexisting lesion couldn't be excluded. Here, we suggest that peritoneal mesothelial cells pinched off during the developmental period might be a source of pigment-producing cells.     

Glioblastomatous transformation of ganglioglioma: case report with reference to molecular genetic and flow cytometric analysis

Gangliogliomas generally behave as benign indolent tumors. However, gangliogliomas undergoing malignant transformation have also been reported. The molecular basis for the malignant transformation of gangliogliomas remains unclear. We describe a case of ganglioglioma, which had transformed to glioblastoma after the gross total resection of the original tumor, in a 4-year-old girl. The present case is unusual in four aspects: (i) it arose from a low-grade ganglioglioma in the absence of previous radiation or chemotherapy, which is the fourth reported case; (ii) the original tumor showed a high proliferative index on flow cytometry but a low Ki-67 labeling index, implying that the application of flow cytometry might play a certain role in predicting biological and clinical behavior of low grade gangliogliomas; (iii) p53 mutation and deletion appeared in the secondary glioblastoma, which was not shown in the original well-differentiated ganglioglioma; and (iv) the transformed glioblastoma showed p16 inactivation detected by methylation and deletion, which are relatively uncommon genetic events in secondary glioblastomas. This is the first report of a genetic alteration in glioblastoma arising from a well differentiated ganglioglioma prior to radiation or chemotherapy. Based on the above findings, irrespective of radiotherapy or chemotherapy, rare recurrence of malignant evolution, especially tumors of high S-phase fraction on flow cytometry, warrants long-term follow-up, even in a well-differentiated ganglioglioma.     

Pathogenesis of generalized melanosis with melanuria and melanoptysis secondary to malignant melanoma

A case of disseminated malignant melanoma with generalized melanosis of the skin and other tissues, melanuria, melanoptysis, and a dark brown blood serum is reported. The reticuloendothelial system contained large amounts of melanin pigment. Lysis of degenerating pigment-loaded melanoma cells in peripheral blood vessels seemed to be of considerable importance in the pigmentation of tissues. Focal pigmentation of capillary endothelium and perivascular deposition of melanin pigment in macrophages and, occasionally, in other cells, was noted. Single cell metastases contributed to melanin pigmentation of most organs, but were not found in sections of the skin. Melanoptysis (black sputum) was due to diffuse melanoma cell infiltration of the lungs, with secondary pigment deposition in macrophages and in bronchial epithelial cells. In this case the 'glomerular melanoma cell emboli' recorded by previous authors consisted of melanin pigment and cell debris. Focal damage of glomeruli affected by pigment emboli is described allowing access of melanoma cell debris (including melanin pigment granules) into glomerular tubules.     

Extensive metastatic leptomeningeal melanomatosis as the first clinical sign of a cutaneous melanoma: morphological correlations between magnetic resonance imaging and autopsy findings. A case report

In recent years, the diagnosis and management of leptomeningeal carcinomatosis have gained increased attention as patients with neoplasms live longer and the condition becomes more common. Conclusive hallmarks of this disease have yet to be identified. We report and discuss a case of massive invasion of the cerebral leptomeninges by neoplastic cells from a malignant melanoma in a shoulder. Symptoms of cerebral dysfunction were the first indication of neoplasm. The onset of symptoms, magnetic resonance imaging, and patient death all occurred within a brief time span. To our knowledge, this is the first case of meningeal melanomatosis in a patient not treated with chemotherapeutic drugs in which the radiologic evidence is virtually synchronous with direct anatomic observation. Thus the images provided with this report may be of use in the radiographic diagnosis of cerebrospinal metastatic colonization.     

Peliosis hepatis associated with lymphoplasmacytic lymphoma: an autopsy case report

A 72-year-old man with no previous history of liver disease was admitted to our university hospital with severe dyspnea, edema of the lower limbs, and weight loss. Within a few days of hospitalization, he died due to severe bleeding in the upper digestive tract. At autopsy, the liver displayed typical gross features of peliosis hepatis. In addition, a diffuse infiltration of liver, spleen, bone marrow, and lymph nodes by lymphoplasmacytic lymphoma was disclosed by light microscopy. In the liver, the neoplastic cells partially filled the peliotic cavities. Peliosis hepatis is a rare liver disease characterized by multiple blood-filled, dilated cavities within the liver parenchyma. Association of lymphoplasmacytic lymphoma and peliosis hepatis has rarely been reported in the literature. The pathologic findings of such an unusual association and a review of the literature are presented.     

Primary pleural angiosarcoma associated with pneumoconiosis: An autopsy case

We report a case of pleural angiosarcoma in an adult male patient confirmed by autopsy and possibly associated with pneumoconiosis. The lesion was characterized by thickened pleura of both lungs with nodular tumors. Histologically, the tumor was composed of spindle‐to‐polygonal epithelioid cells that were positive for CD31, CD34, vimentin, and cytokeratin on immunohistochemical staining but were negative for calretinin. Further examination revealed mix‐dust pathological findings consistent with the existence of pneumoconiosis; dystrophic ossification, anthracosis, and fractal small dust particles were observed in the lung parenchyma and a hilar lymph node. The current case suggests that pneumoconiosis‐associated pathologies may be risk factors for the development of angiosarcoma in the pleura.     

Leptomeningeal carcinomatosis as initial presentation in adenocarcinoma of lung with signet ring cell features: an autopsy case report

Signet ring cell (SRC) features are rare but well-recognized cytological changes of pulmonary adenocarcinoma (PA). PA with SRC features (PA-SRC) is frequently associated with anaplastic lymphoma kinase (ALK) gene rearrangement, and recognition of PA-SRC may be important for the administration of targeted treatment. To the authors’ knowledge, leptomeningeal carcinomatosis (LMC) as an initial presentation of PA-SRC has not yet been reported. We report an autopsy case from a 59-year-old female who presented with intractable headache for 6 weeks and died of LMC as a result of metastatic PA-SRC. Premortem brain MRI showed nonspecific leptomeningeal enhancement. At autopsy, a tan rubbery mass was found in the hilar area of the right lung, which also surrounded the lower trachea and carotid arteries. A right posteromedial middle lobe mass was also found. Leptomeninges were slightly thickened, without discrete masses. Microscopic examination of the lung mass and leptomeninges showed solid sheets and nests of malignant cells with pleomorphic nuclei and frequent SRC features which comprised 50% of the mass. Immunohistochemically, the tumor cells demonstrated strong diffuse expression of cytokeratin (CK)-7, TTF-1, and napsin-A. Immunostains for CK-20 and ALK were negative. These features were consistent with PA-SRC. It has been reported that approximately 70% of PAs demonstrate ALK gene rearrangement when SRCs comprised >10% of the tumor cells. The presence of SRCs can be indicative of a lung primary and, because of frequent ALK gene rearrangement in PA-SRC, proper recognition of PA-SRC may be important in determining whether further testing is advisable (e.g., ALK immunostaining and/or ALK gene rearrangement).     

Malignant epithelioid angiomyolipoma of the kidney in a patient with tuberous sclerosis: an autopsy case report with p53 gene mutation analysis

We report an autopsy case of malignant epithelioid angiomyolipoma in a 36-year-old male tuberous sclerosis patient. He had been diagnosed to have a bilateral renal tumor 20 years previously. The left kidney had been surgically resected at the age of 34, and the left renal tumor was pathologically diagnosed as classic angiomyolipoma and epithelioid angiomyolipoma. He suddenly died of cardiac arrest, and at autopsy the right kidney weighed 7120 g. The tumor presented with massive necrosis invading the inferior vena cava, but was not hemorrhagic. Microscopic examination revealed tumor cells varying in size with a predominantly solid proliferation pattern and marked atypical large cells with vesicular nuclei and abundant eosinophilic cytoplasm. Mitotic figures were often encountered, and atypical forms were also present. Metastatic lesions were identified in the right lung, liver, diaphragm, and mesentery. Immunohistochemical examination showed epithelioid angiomyolipoma cells that were focally reactive for HMB-45 and showed diffuse positive staining for Melan-A. No mutation was detected in the p53 gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis despite diffuse immunoreactivity for p53. This case was proven to be malignant because of the occurrence of distant metastases, and showed that p53 mutations are not always associated with malignant transformation in epithelioid angiomyolipoma.     

Malignant angiomyolipoma in the liver: a case report with pathological and molecular analysis

Malignant angiomyolipoma (AML) of the liver is rare. We report a case of AML with malignant transformation and metastases. A 30-year-old man had developed giant hepatic masses. Microscopically, the periphery of the tumor showed components of classic hepatic AML, but the central region contained atypical epithelioid components with extremely pleomorphic and hyperchromatic nuclei with frequent mitotic figures. Immunohistochemical analysis revealed that the epithelioid cells were positive for HMB-45 and smooth muscle actin. Furthermore, the atypical epithelioid cells displayed P53 immunoreactivity and mutation at exon 7 for p53. The tumor showed a typical monoclonal pattern but no loss of heterozygosity or microsatellite instability. Markedly atypical epithelioid cells with vascular invasion, distant metastasis, and fatal outcome were interpreted as malignant characteristics of hepatic AML. It is suggested that large tumor size, pleomorphic nuclei with high proliferation activity, and P53 immunoreactivity may predict the existence of malignant transformation of hepatic AML.     

Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli

Four cases are described in which spindle-shaped, yellow-brown bodies were seen in the mesenteric lymph nodes of patients with melanosis coli. A comparison of the staining reactions and ultrastructural appearances of the spindle bodies and melanosis pigment suggest that they are related within the broad group of lipofuscins and that the spindle bodies are formed as a result of coalescence of lysosomes containing the pigment.     

Non-Hodgkin's lymphoma presenting with adrenal insufficiency and hypothyroidism: An autopsy case report

A 55-year-old male presented with an Initial manifestation of primary adrenal Insufficlency, hypothyroidism. Computed tomography scans showed enlarged bilateral adrenal glands and thyroid. A pathological diagnosis of diffuse large cell, B cell lymphoma was made by a needle biopsy of the adrenal gland. He was treated with combination chemotherapy and adrenal and thyroid hormone replacement. The lymphoma subsequently involved the central nervous system. He died of pneumonia 8 months after the presentation of the first symptom. The postmortem examination demonstrated a complete regression of lymphoma in the bilateral adrenal glands and thyroid. This Is an extremely rare case of coexistent lymphoma of the adrenal glands and the thyroid presenting with adrenal failure and hypothyroidism.     

Nuclear to cytoplasmic compartment shift of the p33ING1b tumour suppressor protein is associated with malignancy in melanocytic lesions

AIMS: Cutaneous malignant melanoma is an unpredictable neoplasm. Studies of cell cycle and proliferation-associated proteins may help in the understanding of the genesis of melanomas. The tumour suppressor gene TP53 has been shown to be involved in melanomas. However, the incidence of TP53 malfunction in cutaneous melanoma is unclear, and other regulators of cell cycle control are likely to be involved in both the development and progression of melanocytic neoplasia. A candidate is the ING1 gene, which co-operates with TP53 in growth suppression and apoptosis. Thus loss of ING1 function may have similar consequences to loss of TP53 function and may contribute to tumorigenesis. Therefore we have studied the expression of p33ING1b protein in cutaneous melanocytic neoplasia. METHODS AND RESULTS: Sixty-seven melanocytic lesions were studied by immunohistochemistry for the expression of p33ING1b. In our series there was loss of nuclear p33ING1b expression in invasive malignant melanoma compared with normal cutaneous melanocytes or the melanocytes of benign melanocytic naevi. This was associated with an enhancement of cytoplasmic p33ING1b expression which was particularly prominent in invasive malignant melanoma. CONCLUSIONS: Cytoplasmic immunostaining for p33ING1b using MAb GN2 is strongly associated with 'activated' melanocytic lesions; therefore it is possible that this MAb could be of value in diagnostic practice. Furthermore, the reduction in p33ING1b expression and perhaps translocation from the nucleus to the cytoplasm may play a central role in the development and progression of melanomas.     

Melanoma developing in a nevoid melanocytoma with myxoid changes: a case report

Nevoid and myxoid melanoma are rare variants of melanoma; association of the two is a unique finding. Nevoid melanoma is characterized by morphologic resemblance to a nevus, whereas myxoid melanoma demonstrates a basophilic mucinous matrix. We present an atypical case of a melanoma progressing from a nevoid melanocytoma with myxoid changes. A 78-year-old female presented with a pigmented growth on her right thigh. Biopsy demonstrated a biphenotypic melanocytic proliferation composed of a nodule showing epithelioid melanocytes with enlarged nuclei, prominent nucleoli, lack of maturation, and abundant amphophilic cytoplasm with a rare mitotic figure. These findings were suggestive of melanoma along with a nevoid dermal component and myxoid stroma. FISH testing revealed a homozygous loss of 9p21 in the atypical component. SNP-microarray from the nevoid component demonstrated three abnormalities including a gain of whole chromosome 8, as well as loss of a copy of nearly an entire chromosome 9 and 16q most consistent with a melanocytoma.     

A signet‐ring cell melanoma arising from a medium‐sized congenital melanocytic nevus in an adult: A case report and literature review

Patients with congenital nevus, especially giant congenital melanocytic nevus (CMN) measuring >20 cm, are known to be at elevated risk of developing melanomas, especially during the first and second decades of life. Melanomas rarely develop in patients with small and medium‐sized CMNs, but if they do, they occur during the fourth and fifth decades of life. We present a case of a rapidly enlarging signet‐ring cell melanoma (over 3 months) that arose from a medium‐sized CMN in a 57‐year‐old Japanese man. Only 11 other cases of signet‐ring cell melanomas at the primary site have been reported. On the basis of morphology alone, it is difficult to diagnose a nodule appearing in a CMN as a signet‐ring cell melanoma, because even a benign melanocytic nevus can appear as signet‐ring cell morphology. Moreover, a rapidly growing proliferative nodule (PN) more often develops in a CMN than melanoma; PNs may at times exhibit enough atypia to be comparable to melanomas. In our case, loss of p16 expression in the melanoma distinguished it from the nevus cells and was helpful in making the correct diagnosis. Clinical information, such as the patient's age, was also useful in establishing the diagnosis.     

Myoepithelial carcinoma arising in an adenomyoepithelioma of the breast: case report with immunohistochemical and mutational analysis

Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by biphasic proliferation of both epithelial and myoepithelial cells. In rare instances, the epithelial, the myoepithelial or both components of an AME may become malignant. Described herein is the case of a 69-year-old woman who presented with myoepithelial carcinoma of the breast in an AME. Malignancy of myoepithelial component (MEC) was evidenced by the presence of cytological atypia, high mitotic rate, necrosis and local invasion. Immunohistochemical study demonstrated strong expression of P53 and phosphorylated extracellular signal-regulated kinase 1/2 in MEC. Laser capture microdissection technique and mutational analysis further revealed point mutation of the p53 gene (T-->G transversion at codon 270) in this population, but not in glandular epithelial cells or adjacent normal ductal epithelium. No mutations in exons 1 and 2 of the K-, H-, and N-ras genes were identified in any of the neoplastic component. To the authors' knowledge this is the first report of a mutation in the p53 gene in a malignant AME of the breast.