Changing phenotype of gastrointestinal stromal tumours under imatinib mesylate treatment: a potential diagnostic pitfall

AIMS: The diagnosis of gastrointesinal stromal tumours (GISTs) is widely based on morphological features and KIT (CD117) immunoreactivity. Most patients with advanced GISTs show a major clinical response after treatment with imatinib mesylate. The histopathological features of GISTs in patients on prolonged imatinib treatment have, thus far, not been addressed in detail. In this report, we present three patients with metastatic GISTs, who received more than 1 year of therapy with imatinib, and whose tumours changed their morphological and immunohistochemical characteristics during continued treatment with the drug. METHODS AND RESULTS: All three primary GISTs from these patients were classical spindle-type tumours, showing diffuse, strong CD117, CD34, and focal alpha-smooth muscle actin expression. During treatment, two clinically progressive and one clinically stable GIST revealed a diffuse epithelioid, or pseudopapillary epithelioid growth pattern, characterized by rounded cells with eosinophilic cytoplasm and uniform round-to-ovoid nuclei. In addition, GIST specimens from patients on therapy showed complete loss of CD117 immunoreactivity. Remarkably, two of these tumours also became CD34 immunonegative and in one case the progression was accompanied by desmin expression. KIT mutational analysis revealed the presence of distinct exon 11 mutant isoforms in all cases examined, while the same genotype was sustained in the base line and on-therapy tumour specimens, proving the common origin of analysed specimens. CONCLUSIONS: GISTs subject to imatinib treatment can undergo striking (immuno)phenotypic changes, which are not necessarily corroborated by new genotypic modifications. Because these may mimic other tumour types, this feature creates a differential diagnostic challenge, of which the pathologist should be aware.     

Ovarian signet-ring stromal tumor: a potential diagnostic pitfall

Signet-ring stromal tumor is a rare ovarian neoplasm with only 10 reported cases in the literature. We report an unusual case of ovarian signet-ring stromal tumor in a 69-year-old woman who presented with right adnexal mass and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The diagnosis was based on histological, histochemical, immunohistochemical, and electron microscopy characteristics. The main significance is to differentiate this benign tumor from the highly malignant Krukenberg tumor, and this differential diagnosis is discussed.     

N-myristoyltransferase: A potential novel diagnostic marker for colon cancer

Background  

Colon cancer is the second leading cause of cancer deaths in the western world. If detected early, colorectal cancer is one of the most treatable forms of cancer. Unfortunately, very few people are screened. N-myristoyltransferase (NMT) catalyzes myristoylation of various proteins including oncoproteins. We have demonstrated earlier the alteration of NMT activity during the progression of colorectal cancer and established NMT as a putative therapeutic target for cancer.     

Lichenoid tissue reaction in malignant melanoma: a potential diagnostic pitfall

Lichenoid tissue reactions can occur in malignant melanoma and may cause partial regression of the lesion. We studied a series of melanomas to determine how frequently lichenoid tissue reaction obscures the diagnosis of malignant melanoma. We retrospectively reviewed 342 cases of invasive malignant melanoma and melanoma in situ from the head, neck, chest, and back. Of the 342 cases, 23 (6.7%) had a lichenoid tissue reaction obscuring a portion of the lesion. In 6 cases (1.8%), the lichenoid tissue reaction replaced a major portion of the lesion. Knowledge of this phenomenon can prevent misdiagnosis.     

Thyroglobulin immunoreactivity in lymph node histiocytes: a potential diagnostic pitfall

AIMS: Strong thyroglobulin immunoreactivity within sinus histiocytes in a lymph node draining a papillary thyroid carcinoma was observed in a recent case. This prompted the investigation of whether thyroglobulin immunoreactivity is common in regional lymph nodes in cases of thyroid malignancy. METHODS: Eighty seven lymph nodes were studied from 21 cases of thyroid malignancy. These comprised papillary carcinoma (n = 12), follicular carcinoma (n = 4), medullary carcinoma (n = 3), and one case each of squamous and anaplastic carcinoma. Eleven cervical lymph nodes from patients with no evidence of thyroid disease were included as controls. Sections were stained with a monoclonal antibody against thyroglobulin. RESULTS: In the cases of thyroid malignancy, 32 of 87 lymph nodes showed positive staining for thyroglobulin of histiocytes within the subcapsular and medullary sinuses. In an additional four cases, there was positive staining of lymph within lymphatic channels. Positivity was present in at least one node in 15 of 21 cases. There was no positivity in the control cases. There was no correlation between the size of the primary tumour and the presence of thyroglobulin positivity. CONCLUSIONS: Positive staining with antithyroglobulin occurs not uncommonly in sinus histiocytes in lymph nodes draining thyroid tumours. This positivity could be the result of the destruction of normal thyroid follicles, with the release of thyroglobulin, which is taken up by histiocytes, which subsequently drain to local lymph nodes. Pathologists should be aware of this phenomenon and should be careful not to interpret this as metastatic tumour.     

Desmin expression in spindle cell lipomas: a potential diagnostic pitfall

The immunohistochemical analysis of the spindle cell lipomas has been for the most part limited to the study of S-100 protein, CD34, and Bcl-2 reactivity. To evaluate the immunoexpression of desmin and actins in spindle cell lipomas of different histological subtypes a retrospective immunohistochemical study of 25 spindle cell lipomas using archival formalin-fixed, paraffin-embedded tissue was performed. Strong positivity of the spindle cell component for desmin was found in 4 of 25 cases (16%). The expression was diffuse in two cases and focal (in up to 25% of the spindle cells) in the other two. Two of these cases were of the classical type and the other two were angiomatous spindle cell lipomas. Desmin-positive and desmin-negative spindle cells showed no morphological differences. The spindle cell component expressed CD34 in all cases and Bcl-2 in 14 of the 25 cases. There was no immunoreactivity for smooth muscle actin, muscle-specific actin, or S-100 protein. We conclude that a significant proportion of spindle cell lipomas express desmin, and therefore that the immunoreactivity for this antigen does not exclude the diagnosis, even in lesions with nonclassical histological features and/or atypical locations.     

Podoplanin: a novel diagnostic immunohistochemical marker

Podoplanin is a transmembrane mucoprotein recognized by the recently commercially available D2-40 monoclonal antibody. Recent investigations have shown that podoplanin is selectively expressed in lymphatic endothelium as well as lymphangiomas, Kaposi sarcomas, and in a subset of angiosarcomas with probable lymphatic differentiation. Podoplanin has also been shown to be strongly expressed in seminomas, epithelioid mesotheliomas, and hemangioblastomas, and immunostaining for this marker can assist in the diagnosis of these tumors. This article reviews the current information on the applications of podoplanin immunostaining in surgical pathology.