Diagnosis: Dermal scar



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Case 1: 75 y old female with skin lesion

Diagnosis:



  1. Dermal scar

  2. Desmoplastic melanoma

  3. Dermatofibroma

Histology: There is a spindle cell proliferation involving skin dermis and subcutaneous tissue, adjacent to a dermal scar. The cells show mild cytological atypia and mitoses with few atypical forms. The tumor has a focal storiform pattern. In the epidermis above the lesion there is an atypical melanocytic proliferation.

Discussion: Desmoplastic melanoma is rare, representing less than 4% of all melanomas. Due to its fibrosing nature, it may represent a diagnostic pitfall and can be mistaken with other benign fibrosing skin lesions. It usually presents as a firm papule or nodule and pigmentation is absent. It has a predilection for sun damaged skin and usually occurs in older individuals (the age of diagnosis is 10 y later than conventional melanoma). Microscopically, the lesion is composed of spindle cells separated by a collagenous stroma, which can be more or less abundant. An in situ component is often identified. The spindle cells can be bland in some cases; they are usually S100 positive and negative or minimally positive for Mart-1, MITF, HMB45, and tyrosinase. The differential diagnosis includes other malignant lesions such as sarcomatoid carcinoma or sarcoma (leiomyosarcoma, fibrosarcoma, MPNST). Although S100 can be positive in sarcomatoid carcinoma, high molecular weight keratin has not been reported to be positive in melanomas. Fibrosarcoma and leiomyosarcoma are usually S100 negative. The differential diagnosis with MPNST can be more challenging. Desmoplastic melanoma is usually diffusely positive for S100, is accompanied by an epidermal melanocytic component and occurs in sun damaged skin in the head and neck area; whereas MPNST is focally positive for S100, and occurs in deep locations. Clinical history is also helpful in the differential (family history of melanoma vs. Neurofibromatosis). Benign lesions included in the differential diagnosis of desmoplastic melanoma are sclerosing melanocytic nevus, dermal scar, dermatofibroma and neurofibroma. In a scar, the myofibroblasts/fibroblasts are parallel to the epidermis in contrast with desmoplastic melanoma and S100 is negative. S100 is also helpful in the differential with dermatofibroma. Neurofibroma lacks the atypia seen in desmoplastic melanoma. Desmoplasia can be associated with benign nevi such as amelanotic blue nevi, Spitz nevi or other ordinary acquired or congenital nevi with a sclerosing dermal stroma. The morphological features and immunostains can be helpful in these cases. Nevi are symmetric, non infiltrative, with maturation, and with no evidence of atypia (except for Spitz) or mitosis. They can have a junctional component and usually do not extend to the fat (except for congenital nevi). Nevi are positive for Mart-1, MITF and tyrosinase. In the recent literature it has become evident that patients with pure desmoplastic melanomas, as compared with patients with mixed desmoplastic and more cellular components, had longer disease free survival and the difference was most pronounced among thick, deeply infiltrative tumors. The incidence of lymph node metastases in patients with desmoplastic melanoma is lower than that of conventional melanoma; therefore SLN biopsy is not recommended in some institutions. When metastases occur in the lymph nodes or other organs the lesion usually lacks desmoplasia.

Case 2: 68 year old man with right hemicolectomy.

Histology: This is a section from the colon showing a sessile lesion. Within this lesion, the basal crypts appear to be dilated and few crypts are growing parallel to the muscularis mucosa. Serration is seen throughout the colonic glands. There is no evidence of overt dysplasia

Diagnosis:



  1. Sessile serrated adenoma (SSA)

  2. Traditional serrated adenoma (TSA)

  3. Hyperplastic polyp (HPP)

Discussion: SSA is a preneoplastic lesion in the intestine lacking overt dysplasia. Histologically it is characterized by crypts that are dilated and parallel to the muscularis mucosa with an L or T shape. Within the crypts there is increased goblet cells and foveolar epithelium. Serration is seen at the base of the crypts as well as the surface. Mitosis can be seen in the upper third and the surface. In contrast, in HPP, the lower third of the crypts remains narrow and is formed by immature cells and rarely goblet cells. Serration is seen only in the upper half of the crypts. TSA is a different lesion where cytologic dysplasia is always present. It is pedunculated; the main cell has an eosinophilic cytoplasm and a centrally placed nucleus. It also has a somewhat villous architecture. The proposed classification for polyps with serration is: 1- HPP, 2-SSA, 3-TSA, 4-mixed serrated polyp, 5-Sessile Serrated Polyp (SSP; favor one type over the other). SSA is likely to be the precursor lesion for at least some of the colorectal carcinomas with MSI. It seems that SSA progresses to adenocarcinoma in a stepwise manner acquiring cytologic dysplasia. The rate of progression to cancer or recurrence is unknown. Recommendation for treatment: right- sided SSA, remove completely, if not, surveillance and frequent colonoscopy with biopsy. If dysplasia is found surgical excision is recommended. Left -sided: they are small and usually completely removed endoscopically.

Case 3


25 y old female with a mass in the adrenal gland

Histology: The lesion is composed of a proliferation of basophilic cells that are arranged in nests and present in the adrenal gland. There is no evidence of marked atypia or mitosis.

Diagnosis:


  1. Pheochromocytoma

  2. Adrenal cortical adenoma

  3. Carcinoid tumor

Discussion: Pheochomocytomas are uncommon tumors arising from the sympatho-adrenal system. Outside the adrenal they are called paragangliomas. They secrete cathecolamins (E, NE) and their clinical hallmark is hypertension. Pheochromocytomas are easy to diagnose histologically and is positive for neuroendocrine markers. They are mostly benign and the percentage of malignant tumors range from 2.4% to 26%. Benign treated pheochromocytomas have a 5 y survival rate of 95% and a recurrence rate of 10% whereas survival rate in malignant pheochromocytomas is 44%. Traditionally only metastasized tumors have been considered malignant for certain. Therefore it is difficult based on the histology of the tumor to predict its behavior. Hyperchromasia and pleomorphism as well as occasional mitoses can be seen in benign pheochromocytomas. Certain histological features have been associated with malignancy. In one study, malignant pheochromocytomas displayed at least one suspicious feature: confluent necrosis, >5 mitosis/10 HPF, vascular invasion, capsular invasion. Tumors with no metastases but with at least one of these features are considered to be borderline and need closer follow-up.

Case 4


80 y old man with a parotid mass

Diagnosis:



  1. Metastatic malignant melanoma

  2. Myoepithelial carcinoma

  3. Angiosarcoma

  4. Squamous cell carcinoma

Histology: the tumor is composed of sheets of atypical cells seen in the parotid parenchyma and within an adjacent lymph node. The cells have a high n/c ratio with eosinophilic cytoplasm and atypical pleomorphic nuclei with prominent nucleoli. The appearance is monotonous and the cells display focally plasmacytoid features. There is abundant mitotic activity. The tumor cells are positive for p63 and focally for actin, cam5.2 and S100. They are negative for AE1/AE3, HMB45 and Mart-1.

Discussion: the tumor is best classified as a high grade carcinoma with myoepithelial differentiation. Myoepithelial cells are a component of several types of salivary gland tumors: mixed tumors, adenoid cystic carcinoma etc…if the tumor is composed exclusively of myoepithelial cells it is called myoepithelioma. This tumor could be classified into 3 morphological types: spindle, hyaline or plasmacytoid, clear). The tumor is positive for keratin, S100, actin, myosin. They can be benign or malignant. All myoeptheliomas of clear cell type should be regarded as potentially malignant (epi-myoepithelial carcinomas).



Case 5

46 y old woman with a breast mass



Diagnosis:

  1. Medullary carcinoma

  2. Invasive ductal carcinoma with medullary features

  3. Invasive ductal carcinoma, poorly differentiated.

Histology:

Discussion: Medullary carcinoma is one of the recognized special types of breast cancer, although it is very rarely diagnosed. It is defined by the presence of a syncitial growth pattern that represents more than 75% of the tumor, the absence of a glandular component, moderate to marked lymphocytic infiltrate, well circumscribed borders (originally, absence of DCIS used to be a criteria but not anymore). If there is >75% syncitial growth pattern and one or more of the other criteria (but not all) the tumor is called invasive ductal with medullary features or “atypical medullary carcinoma”. The importance to recognize medullary carcinoma as an entity comes from the fact that this subtype has a better prognosis compared to conventional high grade invasive carcinoma. The 5 y and 10 y survival rates are 95% and 84% respectively whereas they are 70% and 58% for the conventional non-medullary carcinoma. These tumors are usually negative for ER, PR and Her-2. Five to 19% of BRCA1 carcinomas are medullary type and a higher proportion display medullary features. On the other hand in a study of medullary carcinomas and atypical medullary carcinomas only 3 patients had BRCA mutation who actually had a personal or a strong family history of breast cancer. Therefore a medullary phenotype by itself does not justify genetic testing.


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